TY - JOUR T1 - Quantitative structure-antitumor activity relationships of camptothecin analogues: cluster analysis and genetic algorithm-based studies. AN - 71204027; 11563924 AB - Topoisomerase 1 (top1) inhibitors are proving useful against a range of refractory tumors, and there is considerable interest in the development of additional top1 agents. Despite crystallographic studies, the binding site and ligand properties that lead to activity are poorly understood. Here we report a unique approach to quantitative structure-activity relationship (QSAR) analysis based on the National Cancer Institute's (NCI) drug databases. In 1990, the NCI established a drug discovery program in which compounds are tested for their ability to inhibit the growth of 60 different human cancer cell lines in culture. More than 70 000 compounds have been screened, and patterns of activity against the 60 cell lines have been found to encode rich information on mechanisms of drug action and drug resistance. Here, we use hierarchical clustering to define antitumor activity patterns in a data set of 167 tested camptothecins (CPTs) in the NCI drug database. The average pairwise Pearson correlation coefficient between activity patterns for the CPT set was 0.70. Coherence between chemical structures and their activity patterns was observed. QSAR studies were carried out using the mean 50% growth inhibitory concentrations (GI(50)) for 60 cell lines as the dependent variables. Different statistical methods, including stepwise linear regression, principal component regression (PCR), partial least-squares regression (PLS), and fully cross-validated genetic function approximation (GFA) were applied to construct quantitative structure-antitumor relationship models. For our data set, the GFA method performed better in terms of correlation coefficients and cross-validation analysis. A number of molecular descriptors were identified as being correlated with antitumor activity. Included were partial atomic charges and three interatomic distances that define the relative spatial dispositions of three significant atoms (the hydroxyl hydrogen of the E-ring, the lactone carbonyl oxygen of the E-ring, and the carbonyl oxygen of the D-ring). The cross-validated r(2) for the final GFA model was 0.783, indicating a predictive QSAR model. JF - Journal of medicinal chemistry AU - Fan, Y AU - Shi, L M AU - Kohn, K W AU - Pommier, Y AU - Weinstein, J N AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/09/27/ PY - 2001 DA - 2001 Sep 27 SP - 3254 EP - 3263 VL - 44 IS - 20 SN - 0022-2623, 0022-2623 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Regression Analysis KW - Drug Screening Assays, Antitumor KW - Tumor Cells, Cultured KW - Humans KW - Enzyme Inhibitors -- chemistry KW - Databases, Factual KW - Algorithms KW - Inhibitory Concentration 50 KW - Cluster Analysis KW - Camptothecin -- chemistry KW - Quantitative Structure-Activity Relationship KW - Camptothecin -- pharmacology KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71204027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Quantitative+structure-antitumor+activity+relationships+of+camptothecin+analogues%3A+cluster+analysis+and+genetic+algorithm-based+studies.&rft.au=Fan%2C+Y%3BShi%2C+L+M%3BKohn%2C+K+W%3BPommier%2C+Y%3BWeinstein%2C+J+N&rft.aulast=Fan&rft.aufirst=Y&rft.date=2001-09-27&rft.volume=44&rft.issue=20&rft.spage=3254&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A virus discovery method incorporating DNase treatment and its application to the identification of two bovine parvovirus species AN - 18094474; 5182313 AB - Identification of previously unrecognized viral agents in serum or plasma samples is of great medical interest but remains a major challenge, primarily because of abundant host DNA. The current methods, library screening or representational difference analysis (RDA), are very laborious and require selected sample sets. We have developed a simple and reproducible method for discovering viruses in single serum samples that is based on DNase treatment of the serum followed by restriction enzyme digestion and sequence-independent single primer amplification (SISPA) of the fragments, and have evaluated its performance on known viruses. Both DNA viruses and RNA viruses at a concentration of approximately 10 super(6) genome equivalents per ml were reproducibly identified in 50 mu l of serum. While evaluating the method, two previously unknown parvoviruses were discovered in the bovine sera used as diluent. The near complete genome sequence of each virus was determined; their classification as two species (provisionally named bovine parvoviruses 2 and 3) was confirmed by phylogenetic analysis. Both viruses were found to be frequent contaminants of commercial bovine serum. DNase treatment of serum samples may prove to be a very useful tool for virus discovery. The DNase-SISPA method is suitable for screening of a large number of samples and also enables rapid sequence determination of high-titer viruses. JF - Proceedings of the National Academy of Sciences, USA AU - Allander, T AU - Emerson, SU AU - Engle, R E AU - Purcell, R H AU - Bukh, J AD - Sections for Hepatitis Viruses and Molecular Hepatitis, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, jbukh@niaid.nih.gov Y1 - 2001/09/25/ PY - 2001 DA - 2001 Sep 25 SP - 11609 EP - 11614 VL - 98 IS - 20 SN - 0027-8424, 0027-8424 KW - protocols KW - deoxyribonuclease KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Phylogeny KW - Bovine parvovirus KW - RNA viruses KW - DNA viruses KW - A 01114:Viruses KW - N 14712:DNases KW - V 22031:Viral nucleic acids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18094474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+virus+discovery+method+incorporating+DNase+treatment+and+its+application+to+the+identification+of+two+bovine+parvovirus+species&rft.au=Allander%2C+T%3BEmerson%2C+SU%3BEngle%2C+R+E%3BPurcell%2C+R+H%3BBukh%2C+J&rft.aulast=Allander&rft.aufirst=T&rft.date=2001-09-25&rft.volume=98&rft.issue=20&rft.spage=11609&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.211424698 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bovine parvovirus; Phylogeny; DNA viruses; RNA viruses DO - http://dx.doi.org/10.1073/pnas.211424698 ER - TY - JOUR T1 - The time-course of electrocardiographic interbeat interval dynamics in alcoholic subjects after short-term abstinence. AN - 71184170; 11567653 AB - Alcohol dependence has been correlated with decreases in heart rate variability. However, the time course of recovery of heart rate variability after cessation of alcohol consumption is unknown. We used electrocardiogram (ECG) data serially obtained from a population of detoxifying alcoholic subjects to determine the Hurst exponent of the ECG interbeat interval time series. Higher values of the Hurst exponent are associated with decreased heart rate variability when H< or =0.5. We tested a series of response-surface models relating the Hurst exponent (H) thus obtained to the following independent variables: the time interval T (days since last use of alcohol), A (age in years at time of admission), and gender. The best-fit model was: H(T)=(KA+H(m)T+H(f)T)/(1+T), F=5.2, P(F)G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of TGF-beta1+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. JF - Toxicology letters AU - McKenna, I M AU - Ramakrishna, G AU - Diwan, B A AU - Kang, Y AU - Shiao, Y H AU - Wakefield, L M AU - Powell, D A AU - Anderson, L M AU - Jakowlew, S B AD - Office of Pollution Prevention and Toxic Substances, US Environmental Protection Agency, Washington, DC 20460, USA. mckennai@mail.nih.gov Y1 - 2001/09/15/ PY - 2001 DA - 2001 Sep 15 SP - 151 EP - 158 VL - 123 IS - 2-3 SN - 0378-4274, 0378-4274 KW - Carcinogens KW - 0 KW - DNA, Neoplasm KW - Tgfb1 protein, mouse KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Urethane KW - 3IN71E75Z5 KW - Index Medicus KW - Animals KW - Carcinogens -- administration & dosage KW - DNA Mutational Analysis KW - Mice KW - Polymorphism, Single-Stranded Conformational KW - Urethane -- administration & dosage KW - Genotype KW - DNA, Neoplasm -- chemistry KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Mutagenicity Tests KW - Heterozygote KW - Adenoma -- chemically induced KW - Mice, Inbred C57BL KW - Carcinogenicity Tests KW - Crosses, Genetic KW - DNA, Neoplasm -- genetics KW - Adenoma -- genetics KW - Mutation KW - Male KW - Female KW - Carcinoma -- chemically induced KW - Carcinoma -- genetics KW - Genes, ras -- genetics KW - Genes, ras -- drug effects KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Genetic Predisposition to Disease KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72210981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Heterozygous+inactivation+of+TGF-beta1+increases+the+susceptibility+to+chemically+induced+mouse+lung+tumorigenesis+independently+of+mutational+activation+of+K-ras.&rft.au=McKenna%2C+I+M%3BRamakrishna%2C+G%3BDiwan%2C+B+A%3BKang%2C+Y%3BShiao%2C+Y+H%3BWakefield%2C+L+M%3BPowell%2C+D+A%3BAnderson%2C+L+M%3BJakowlew%2C+S+B&rft.aulast=McKenna&rft.aufirst=I&rft.date=2001-09-15&rft.volume=123&rft.issue=2-3&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-16 N1 - Date created - 2001-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of c-myc overexpression and hyperproliferation with arsenite-induced malignant transformation. AN - 71180421; 11559025 AB - Numerous studies link arsenic exposure to human cancers in a variety of tissues, including the liver. However, inorganic arsenic has never been unequivocally shown to be an animal carcinogen, and its carcinogenic mechanism remains undefined. Our previous studies indicate that chronic (> or =18 weeks), low-level (125 to 500 nM) exposure to arsenite induces malignant transformation in the normally nontumorigenic rat liver epithelial cell line (TRL 1215), and these chronic arsenic-exposed (CAsE) cells produce invasive and metastatic tumors upon inoculation into nude mice. In addition, a prior microarray screening analysis of aberrant gene expression showed several oncogenes were overexpressed in CAsE cells exposed to 500 nM arsenite, including a prominent overexpression of the protooncogene c-myc, as well as genes related to cell proliferation. Thus, to better understand the mechanism of arsenic carcinogenesis, we studied the role of c-myc overexpression in arsenite-induced cell transformation. The upregulation of c-myc was confirmed by RT-PCR at the transcription level and by Western blot analysis for the translation product. Further analysis showed that arsenite produced significant increases in the steady-state expression of c-myc in a time- and concentration-dependent manner during the malignant transformation process. The level of c-myc expression was highly correlated (r = 0.988) with tumor formation after inoculation of CAsE cells into nude mice and was also highly correlated (r = 0.997) with genomic DNA hypomethylation. CAsE cells showed a high cell proliferation rate in a fashion related to the level of arsenic exposure. The expression of c-myc was highly correlated with cellular hyperproliferation (r = 0.961). Consistent with the enhanced proliferation both proliferating cell nuclear antigen and cyclin D1 were overexpressed in CAsE cells. In summary, a prominent overexpression of c-myc, a gene frequently activated during hepatocarcinogenesis, is strongly correlated with several events possibly associated with arsenic-induced malignant transformation, including hyperproliferation, DNA hypomethylation and tumor formation upon inoculation into nude mice. These correlations provide convincing evidence c-myc overexpression is mechanistically important in arsenic-induced malignant transformation in this model system. JF - Toxicology and applied pharmacology AU - Chen, H AU - Liu, J AU - Zhao, C Q AU - Diwan, B A AU - Merrick, B A AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute (NCI) at National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, USA. Y1 - 2001/09/15/ PY - 2001 DA - 2001 Sep 15 SP - 260 EP - 268 VL - 175 IS - 3 SN - 0041-008X, 0041-008X KW - Arsenites KW - 0 KW - Carcinogens KW - Proto-Oncogene Proteins c-myc KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - Index Medicus KW - Animals KW - Hepatocytes -- drug effects KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Hepatocytes -- pathology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Neoplasms, Experimental -- pathology KW - Neoplasm Transplantation KW - Rats KW - DNA Methylation -- drug effects KW - Up-Regulation KW - Time Factors KW - Cell Line KW - Gene Expression -- drug effects KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Carcinogens -- toxicity KW - Proto-Oncogene Proteins c-myc -- genetics KW - Cell Transformation, Neoplastic -- drug effects KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71180421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Association+of+c-myc+overexpression+and+hyperproliferation+with+arsenite-induced+malignant+transformation.&rft.au=Chen%2C+H%3BLiu%2C+J%3BZhao%2C+C+Q%3BDiwan%2C+B+A%3BMerrick%2C+B+A%3BWaalkes%2C+M+P&rft.aulast=Chen&rft.aufirst=H&rft.date=2001-09-15&rft.volume=175&rft.issue=3&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis. AN - 71173865; 11559530 AB - The expression of genes involved in p53-mediated apoptosis was studied using cDNA microarray after treating isogenic cell lines with either ionizing radiation or doxorubicin. Most of the known p53 transcriptional activation target genes clustered in a functional category defined by early and p53-dependent induction, regardless of the type of stress. Apoptotic protease activating factor-1 (APAF-1) emerged from this analysis as a novel p53 target gene. Genomic sequences upstream of the APAF-1 transcription start site contain a classic p53-responsive element that bound to p53. Consistently, p53 directly induced APAF-1 gene expression. Furthermore, DNA damage-mediated induction of APAF-1 mRNA and protein expression, accompanied by apoptosis, were strictly dependent on wild-type p53 function. These data are consistent with the hypothesis that APAF-1 is an essential downstream effector of p53-mediated apoptosis. JF - Cancer research AU - Robles, A I AU - Bemmels, N A AU - Foraker, A B AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/09/15/ PY - 2001 DA - 2001 Sep 15 SP - 6660 EP - 6664 VL - 61 IS - 18 SN - 0008-5472, 0008-5472 KW - APAF1 protein, human KW - 0 KW - Apoptotic Protease-Activating Factor 1 KW - Proteins KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Transcriptional Activation -- radiation effects KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Multigene Family KW - Transcriptional Activation -- drug effects KW - Colorectal Neoplasms -- genetics KW - Gene Expression Profiling KW - Tumor Cells, Cultured KW - Colorectal Neoplasms -- pathology KW - Lymphocytes -- radiation effects KW - Transcriptional Activation -- genetics KW - Lymphocytes -- physiology KW - Lymphocytes -- drug effects KW - Cell Line KW - Apoptosis -- genetics KW - DNA Damage KW - Tumor Suppressor Protein p53 -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71173865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=APAF-1+is+a+transcriptional+target+of+p53+in+DNA+damage-induced+apoptosis.&rft.au=Robles%2C+A+I%3BBemmels%2C+N+A%3BForaker%2C+A+B%3BHarris%2C+C+C&rft.aulast=Robles&rft.aufirst=A&rft.date=2001-09-15&rft.volume=61&rft.issue=18&rft.spage=6660&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis. AN - 71173114; 11559531 AB - The transforming growth factor-beta (TGF-beta) receptor complex and its downstream signaling intermediates constitute a tumor suppressor pathway. In many cancers, expression of TGF-beta type II receptor (TbetaR-II) is markedly decreased. In the present study, we show that the hepatocytes isolated from 15-day-old, but not 9-month-old, mice heterozygous for the deletion of the TbetaR-II gene are slightly less sensitive to the growth-inhibitory effect of TGF-beta when compared with wild-type littermates of same age. In addition, the proliferation index of hepatocytes as indicated by bromodeoxyuridine incorporation is mildly increased in the heterozygous mice. These subtle changes in cellular phenotype did not result in either gross or microscopic abnormality of the liver. The treatment of these mice with the chemical carcinogen, diethylnitrosamine, results in a significantly enhanced tumorigenesis in the liver when compared with the wild-type littermates. Our results demonstrate the gene-dosage effect of TbetaR-II and indicate that the reduced expression of TbetaR-II in mice increases susceptibility to tumorigenesis in the liver. JF - Cancer research AU - Im, Y H AU - Kim, H T AU - Kim, I Y AU - Factor, V M AU - Hahm, K B AU - Anzano, M AU - Jang, J J AU - Flanders, K AU - Haines, D C AU - Thorgeirsson, S S AU - Sizeland, A AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2001/09/15/ PY - 2001 DA - 2001 Sep 15 SP - 6665 EP - 6668 VL - 61 IS - 18 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Tgfb1 protein, mouse KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Transforming Growth Factor beta -- biosynthesis KW - Animals KW - Liver -- metabolism KW - Mice KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Genes, cdc -- physiology KW - Liver -- physiology KW - Pregnancy KW - Phenobarbital -- pharmacology KW - Liver -- drug effects KW - Heterozygote KW - Mice, Inbred C57BL KW - Genetic Predisposition to Disease KW - Transforming Growth Factor beta -- genetics KW - Gene Dosage KW - Female KW - Male KW - Receptors, Transforming Growth Factor beta -- genetics KW - Liver Neoplasms, Experimental -- genetics KW - Liver Neoplasms, Experimental -- metabolism KW - Liver Neoplasms, Experimental -- chemically induced KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71173114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Heterozygous+mice+for+the+transforming+growth+factor-beta+type+II+receptor+gene+have+increased+susceptibility+to+hepatocellular+carcinogenesis.&rft.au=Im%2C+Y+H%3BKim%2C+H+T%3BKim%2C+I+Y%3BFactor%2C+V+M%3BHahm%2C+K+B%3BAnzano%2C+M%3BJang%2C+J+J%3BFlanders%2C+K%3BHaines%2C+D+C%3BThorgeirsson%2C+S+S%3BSizeland%2C+A%3BKim%2C+S+J&rft.aulast=Im&rft.aufirst=Y&rft.date=2001-09-15&rft.volume=61&rft.issue=18&rft.spage=6665&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Error rate and specificity of human and murine DNA polymerase eta. AN - 71169109; 11554790 AB - We describe here the error specificity of mammalian DNA polymerase eta (pol eta), an enzyme that performs translesion DNA synthesis and may participate in somatic hypermutation of immunoglobulin genes. Both mouse and human pol eta lack intrinsic proofreading exonuclease activity and both copy undamaged DNA inaccurately. Analysis of more than 1500 single-base substitutions by human pol eta indicates that error rates for all 12 mismatches are high and variable depending on the composition and symmetry of the mismatch and its location. pol eta also generates tandem base substitutions at an unprecedented rate, and kinetic analysis indicates that it extends a tandem double mismatch about as efficiently as other replicative enzymes extend single-base mismatches. This ability to use an aberrant primer terminus and the high rate of single and double-base substitutions support the idea that pol eta may forego strict shape complementarity in order to facilitate highly efficient lesion bypass. Relaxed discrimination is further indicated by pol eta infidelity for a wide variety of nucleotide deletion and addition errors. The nature and location of these errors suggest that some may be initiated by strand slippage, while others result from additional mechanisms. JF - Journal of molecular biology AU - Matsuda, T AU - Bebenek, K AU - Masutani, C AU - Rogozin, I B AU - Hanaoka, F AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2001/09/14/ PY - 2001 DA - 2001 Sep 14 SP - 335 EP - 346 VL - 312 IS - 2 SN - 0022-2836, 0022-2836 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Point Mutation -- genetics KW - Animals KW - DNA Mutational Analysis KW - Humans KW - Mice KW - Base Pair Mismatch -- genetics KW - DNA Damage -- genetics KW - Frameshift Mutation -- genetics KW - Lac Operon -- genetics KW - Base Sequence KW - Genes, Immunoglobulin -- genetics KW - Kinetics KW - Sequence Deletion -- genetics KW - Molecular Sequence Data KW - Templates, Genetic KW - Substrate Specificity KW - Mutagenesis -- genetics KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71169109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Error+rate+and+specificity+of+human+and+murine+DNA+polymerase+eta.&rft.au=Matsuda%2C+T%3BBebenek%2C+K%3BMasutani%2C+C%3BRogozin%2C+I+B%3BHanaoka%2C+F%3BKunkel%2C+T+A&rft.aulast=Matsuda&rft.aufirst=T&rft.date=2001-09-14&rft.volume=312&rft.issue=2&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 15-lipoxygenase-1 metabolites down-regulate peroxisome proliferator-activated receptor gamma via the MAPK signaling pathway. AN - 71157187; 11447213 AB - Human colon tumors have elevated levels of 15-lipoxygenase-1 (15-LO-1), suggesting that 15-LO-1 may play a role in the development of colorectal cancer. Also, 15-LO-1 metabolites can up-regulate epidermal growth factor signaling pathways, which results in an increase in mitogenesis. However, metabolites of 15-LO-1 can serve as ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), and activation of this receptor causes most colon cancer cell lines to undergo a differentiative response and reverse their malignant phenotype. Hence, the role 15-LO-1 plays in colon cancer is not clear. To clarify the role of 15-LO-1 in carcinogenesis, the effect of 15-LO-1 and its metabolites on epidermal growth factor signaling and PPARgamma was investigated. In HCT-116 cells, exogenously added 15-LO-1 metabolites, 13-(S)-hydroxyoctadecadienoic acid, 13-(R)-hydroxyoctadecadienoic acid, and 13-(S)-hydroperoxyoctadecadienoic acid, up-regulated the MAPK signaling pathway, and an increase in PPARgamma phosphorylation was observed. Furthermore, in stable overexpressing 15-LO-1 HCT-116 cells, which produce endogenous 15-LO-1 metabolites, an up-regulation in mitogen-activated protein kinase and PPARgamma phosphorylation was observed. Incubation with a MAPK inhibitor ablated MAPK and PPARgamma phosphorylation. The 15-LO-1 up-regulates MAPK activity and increases PPARgamma phosphorylation, resulting in a down-regulation of PPARgamma activity. Thus, 15-LO-1 metabolites may not only serve as ligands for PPARgamma but can down-regulate PPARgamma activity via the MAPK signaling pathway. JF - The Journal of biological chemistry AU - Hsi, L C AU - Wilson, L AU - Nixon, J AU - Eling, T E AD - Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/09/14/ PY - 2001 DA - 2001 Sep 14 SP - 34545 EP - 34552 VL - 276 IS - 37 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Linoleic Acids KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Index Medicus KW - Tumor Cells, Cultured KW - Phosphorylation KW - Down-Regulation KW - Dose-Response Relationship, Drug KW - Colonic Neoplasms -- etiology KW - Humans KW - Linoleic Acids -- pharmacology KW - Colonic Neoplasms -- enzymology KW - MAP Kinase Signaling System KW - Isoenzymes -- physiology KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Arachidonate 15-Lipoxygenase -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71157187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=15-lipoxygenase-1+metabolites+down-regulate+peroxisome+proliferator-activated+receptor+gamma+via+the+MAPK+signaling+pathway.&rft.au=Hsi%2C+L+C%3BWilson%2C+L%3BNixon%2C+J%3BEling%2C+T+E&rft.aulast=Hsi&rft.aufirst=L&rft.date=2001-09-14&rft.volume=276&rft.issue=37&rft.spage=34545&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - From carcinogenesis to clinical interventions for cancer prevention AN - 18209828; 5276466 AB - During the last three decades, the scientific community has made immense progress in acquiring the knowledge needed to prevent cancer. Pioneering research helped to identify potential causes of cancer, particularly environmental factors such as diet, and provided insight regarding their mechanisms-of-action. Concurrently, promising inhibitors of cancer that appeared able to either arrest or reverse cancer development by interfering with one or more steps in the process of carcinogenesis were identified and systematically evaluated for their potential as chemopreventive agents. Numerous agents determined to be safe and effective in preclinical trials have been and continue to be tested in Phase I, II, and III clinical interventions for cancers at various sites, including breast, colon, prostate, esophagus, mouth, lung, cervix, endometrium, ovary, liver, bladder, and skin. The development of valid intermediate biomarkers that can serve as surrogate endpoints for clinical disease is urgently needed to accelerate advances in clinical trials for cancer prevention. JF - Toxicology AU - Greenwald, P AD - Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2040, Bethesda, MD 20892-7309, USA, pg37g@nih.gov Y1 - 2001/09/14/ PY - 2001 DA - 2001 Sep 14 SP - 37 EP - 45 VL - 166 IS - 1-2 SN - 0300-483X, 0300-483X KW - prevention KW - man KW - Toxicology Abstracts KW - Reviews KW - Carcinogenesis KW - Cancer KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18209828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=From+carcinogenesis+to+clinical+interventions+for+cancer+prevention&rft.au=Greenwald%2C+P&rft.aulast=Greenwald&rft.aufirst=P&rft.date=2001-09-14&rft.volume=166&rft.issue=1-2&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; Cancer; Reviews ER - TY - JOUR T1 - Safety and immunogenicity of live attenuated quadrivalent human-bovine (UK) reassortant rotavirus vaccine administered with childhood vaccines to infants AN - 18181106; 5207261 AB - The safety and immunogenicity of an orally administered, live rotavirus vaccine comprised of four strains, each with a titer of 10 super(5.3) or 10 super(5.8) pfu, and each having 10 genes from the UK bovine strain and the VP7 gene from human rotavirus serotype 1, 2, 3, or 4, were evaluated in adults, young children and infants in randomized, double-blind phase 1 trails. Three doses of rotavirus vaccine or placebo given with childhood immunizations to infants at 2, 4, and 6 months of age were well tolerated and did not inhibit antibody responses to childhood vaccines which included DTP, Hib, hepatitis B and OPV. Serum rotavirus antibody responses were detected in 12 of 20 infants after 1 dose, and in 19/19 of the vaccinees after three doses. Neutralizing antibody responses were detected more often against the bovine rotavirus UK strain (95%) than to human rotavirus VP7 serotypes 1 (37%), 2 (32%), 3 (32%) or 4 (32%). The efficacy of this quadrivalent rotavirus vaccine needs to be evaluated further. JF - Vaccine AU - Clements-Mann, M L AU - Dudas, R AU - Hoshino, Y AU - Nehring, P AU - Sperber, E AU - Wagner, M AU - Stephens, I AU - Karron, R AU - Deforest, A AU - Kapikian, A Z AD - Laboratory of Infectious Diseases, National Institute of Allergy Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, akapikian@nih.niaid.gov Y1 - 2001/09/14/ PY - 2001 DA - 2001 Sep 14 SP - 4676 EP - 4684 VL - 19 IS - 32 SN - 0264-410X, 0264-410X KW - man KW - cattle KW - VP7 protein KW - vaccines KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts; Immunology Abstracts KW - Risk assessment KW - Rotavirus KW - Age KW - Human rotavirus KW - Safety KW - Attenuation KW - Bovine rotavirus KW - Antibody response KW - Children KW - Immunogenicity KW - Vaccines KW - Infants KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18181106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Safety+and+immunogenicity+of+live+attenuated+quadrivalent+human-bovine+%28UK%29+reassortant+rotavirus+vaccine+administered+with+childhood+vaccines+to+infants&rft.au=Clements-Mann%2C+M+L%3BDudas%2C+R%3BHoshino%2C+Y%3BNehring%2C+P%3BSperber%2C+E%3BWagner%2C+M%3BStephens%2C+I%3BKarron%2C+R%3BDeforest%2C+A%3BKapikian%2C+A+Z&rft.aulast=Clements-Mann&rft.aufirst=M&rft.date=2001-09-14&rft.volume=19&rft.issue=32&rft.spage=4676&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Rotavirus; Bovine rotavirus; Human rotavirus; Children; Infants; Risk assessment; Vaccines; Age; Antibody response; Immunogenicity; Attenuation; Safety ER - TY - JOUR T1 - Modulation of Glucose-6-phosphate Dehydrogenase Activity and Expression Is Associated with Aryl Hydrocarbon Resistance in Vitro AN - 17895777; 5169684 AB - The mutagenic effect of environmental carcinogens has been well documented in animal models and in human studies but the mechanisms involved in preventing carcinogen insult have not been fully elucidated. In this study we examined the molecular and biochemical changes associated with carcinogen resistance in a series of aryl hydrocarbon-resistant MCF-7 cell lines developed by exposure to benzo[a]pyrene (BP). The cell lines were designated as AH super(R40), AH super(R100), and AH super(R200) to denote their increasing fold resistance to BP compared with wild type cells. These cell lines were also resistant to another aryl hydrocarbon (AH), dimethylbenz[a]anthracene, but not to pleiotropic drugs (doxorubicin, vinblastine, and taxol). The resistant cell lines showed an increase in the level of the primary intracellular antioxidant, reduced glutathione, corresponding to increasing AH resistance. However, there was no change in glutathione reductase activity. The generation of reduced glutathione requires NADPH, and we therefore examined the activity and expression of the rate-limiting enzyme in NADPH production, glucose-6-phosphate dehydrogenase (G6PD). An increase in G6PD specific activity was associated with increasing aryl hydrocarbon resistance. This was due to an increased expression of G6PD in resistant cells, which was demonstrated by increases in both protein and mRNA levels. However, there was no increase in the transcription rate of G6PD in the resistant cell lines, indicating that the increase G6PD expression is due to a post-transcriptional modulation, which was confirmed by actinomycin D chase experiments. These results demonstrate that modulation of G6PD expression and activity is an important mechanism in AH resistance. JF - Journal of Biological Chemistry AU - Yeh, G C AU - Daschner, P J AU - Lopaczynska, J AU - MacDonald, C J AU - Ciolino, H P AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, NCI at Frederick, National Institutes of Health, Frederick, Maryland 21702, yeh@ncifcrf.gov Y1 - 2001/09/14/ PY - 2001 DA - 2001 Sep 14 SP - 34708 EP - 34713 VL - 276 IS - 37 SN - 0021-9258, 0021-9258 KW - Dactinomycin KW - actinomycin D KW - animal models KW - aryl hydrocarbons KW - dimethylbenz(a)anthracene KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - Gene expression KW - Glutathione KW - Hydrocarbons KW - 9,10-Dimethyl-1,2-benzanthracene KW - Animal models KW - Glucose-6-phosphate 1-dehydrogenase KW - Benzo(a)pyrene KW - Carcinogens KW - X 24190:Polycyclic hydrocarbons KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Modulation+of+Glucose-6-phosphate+Dehydrogenase+Activity+and+Expression+Is+Associated+with+Aryl+Hydrocarbon+Resistance+in+Vitro&rft.au=Yeh%2C+G+C%3BDaschner%2C+P+J%3BLopaczynska%2C+J%3BMacDonald%2C+C+J%3BCiolino%2C+H+P&rft.aulast=Yeh&rft.aufirst=G&rft.date=2001-09-14&rft.volume=276&rft.issue=37&rft.spage=34708&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Gene expression; Hydrocarbons; Glutathione; 9,10-Dimethyl-1,2-benzanthracene; Glucose-6-phosphate 1-dehydrogenase; Animal models; Benzo(a)pyrene; Carcinogens ER - TY - JOUR T1 - Novel domains of the prokaryotic two-component signal transduction systems AN - 18098678; 5183027 AB - The archetypal two-component signal transduction systems include a sensor histidine kinase and a response regulator, which consists of a receiver CheY-like domain and a DNA-binding domain. Sequence analysis of the sensor kinases and response regulators encoded in complete bacterial and archaeal genomes revealed complex domain architectures for many of them and allowed the identification of several novel conserved domains, such as PAS, GAF, HAMP, GGDEF, EAL, and HD-GYP. All of these domains are widely represented in bacteria, including 19 copies of the GGDEF domain and 17 copies of the EAL domain encoded in the Escherichia coli genome. In contrast, these novel signaling domains are much less abundant in bacterial parasites and in archaea, with none at all found in some archaeal species. This skewed phyletic distribution suggests that the newly discovered complexity of signal transduction systems emerged early in the evolution of bacteria, with subsequent massive loss in parasites and some horizontal dissemination among archaea. Only a few proteins containing these domains have been studied experimentally, and their exact biochemical functions remain obscure; they may include transformations of novel signal molecules, such as the recently identified cyclic diguanylate. Recent experimental data provide the first direct evidence of the participation of these domains in signal transduction pathways, including regulation of virulence genes and extracellular enzyme production in the human pathogens Bordetella pertussis and Borrelia burgdorferi and the plant pathogen Xanthomonas campestris. Gene-neighborhood analysis of these new domains suggests their participation in a variety of processes, from mercury and phage resistance to maintenance of virulence plasmids. It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold. JF - FEMS Microbiology Letters AU - Galperin, MY AU - Nikolskaya, AN AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 20894 Bethesda, MD USA Y1 - 2001/09/11/ PY - 2001 DA - 2001 Sep 11 SP - 11 EP - 21 PB - Elsevier Science VL - 203 IS - 1 SN - 0378-1097, 0378-1097 KW - CheY protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Phages KW - Borrelia burgdorferi KW - DNA-binding protein KW - Plasmids KW - Virulence KW - Bordetella pertussis KW - Reviews KW - Xanthomonas campestris KW - Signal transduction KW - N 14100:Reviews KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18098678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Novel+domains+of+the+prokaryotic+two-component+signal+transduction+systems&rft.au=Galperin%2C+MY%3BNikolskaya%2C+AN%3BKoonin%2C+E+V&rft.aulast=Galperin&rft.aufirst=MY&rft.date=2001-09-11&rft.volume=203&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Bordetella pertussis; Xanthomonas campestris; Reviews; Signal transduction; DNA-binding protein; Virulence; Plasmids; Phages ER - TY - JOUR T1 - In vivo mechanism-based inactivation of S-adenosylmethionine decarboxylases from Escherichia coli, Salmonella typhimurium, Saccharomyces cerevisiae AN - 17891519; 5173287 AB - S-adenosylmethionine decarboxylase (AdoMetDC), a key enzyme in the biosynthesis of spermidine and spermine, is first synthesized as a proenzyme, which is cleaved posttranslationally to form alpha and beta subunits. The alpha subunit contains a covalently bound pyruvoyl group derived from serine that is essential for activity. With the use of an Escherichia coli overexpression system, we have purified AdoMetDCs encoded by the E. coli, Saccharomyces cerevisiae, and Salmonella typhimurium genes. Unexpectedly we found by mass spectrometry that these enzymes had been modified posttranslationally in vivo by a mechanism-based "suicide" inactivation. A large percentage of the alpha subunit of each enzyme had been modified in vivo to give peaks with masses m/z = 57 plus or minus 1 and m/z = 75 plus or minus 1 daltons higher than the parent peak. AdoMetDC activity decreased markedly during overexpression concurrently with the increase of the additional peaks for the alpha subunit. Sequencing of a tryptic fragment by tandem mass spectrometry showed that Cys-140 was modified with a +75 plus or minus 1 adduct, which is probably derived from the reaction product. Comparable modification of the alpha subunit was also observed in in vitro experiments after incubation with the substrate or with the reaction product, which is consistent with the in vitro alkylation of E. coli AdoMetDC reported by Diaz and Anton [Diaz, E. & Anton, D. L. (1991) Biochemistry 30, 4078-4081]. JF - Proceedings of the National Academy of Sciences, USA AU - Li, Y AU - Hess, S AU - Pannell, L K AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, tabor@helix.nih.gov Y1 - 2001/09/11/ PY - 2001 DA - 2001 Sep 11 SP - 10578 EP - 10583 VL - 98 IS - 19 SN - 0027-8424, 0027-8424 KW - budding yeast KW - spermidine KW - Genetics Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Spermine KW - Overexpression KW - Escherichia coli KW - Adenosylmethionine decarboxylase KW - Salmonella typhimurium KW - Mass spectroscopy KW - Saccharomyces cerevisiae KW - K 03020:Fungi KW - J 02728:Enzymes KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17891519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=In+vivo+mechanism-based+inactivation+of+S-adenosylmethionine+decarboxylases+from+Escherichia+coli%2C+Salmonella+typhimurium%2C+Saccharomyces+cerevisiae&rft.au=Li%2C+Y%3BHess%2C+S%3BPannell%2C+L+K&rft.aulast=Li&rft.aufirst=Y&rft.date=2001-09-11&rft.volume=98&rft.issue=19&rft.spage=10578&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.181341198 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Spermine; Overexpression; Adenosylmethionine decarboxylase; Mass spectroscopy; Escherichia coli; Salmonella typhimurium; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1073/pnas.181341198 ER - TY - JOUR T1 - Molecular cloning and characterization of human nonsteroidal anti-inflammatory drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3. AN - 71144926; 11445565 AB - Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is known to be associated with anti-tumorigenic activity and belongs to the transforming growth factor-beta superfamily. In the present study, we cloned the promoter region (-3500 to +41) and investigated the transcriptional regulatory mechanisms of the basal expression of the human NAG-1 gene. Several potential transcription factor-binding sites in this region were identified. Based on the results from clones of nested deletions, the construct between -133 and +41 base pairs contains three Sp1-binding sites (Sp1-A, Sp1-B, and Sp1-C), which confer basal transcription specific activity of NAG-1 expression. When the Sp1-C site was mutated (GG to TT), a 60-80% decrease in promoter activity was observed in HCT-116 cells. Gel shift, co-transfection, and chromatin immunoprecipitation assays showed that the Sp transcription factors bind to the Sp1-binding sites and transactivate NAG-1 expression. In addition, chicken ovalbumin upstream promoter-transcription factor 1 can interact with the C-terminal region of Sp1 and Sp3 proteins and induce NAG-1 promoter activity through Sp1 and Sp3 transcription factors. These results identify the critical regulatory regions for the human NAG-1 basal promoter. Furthermore, the results suggest that the level of expression of the NAG-1 gene will depend on the availability of Sp proteins and on co-factors such as chicken ovalbumin upstream promoter-transcription factor 1. JF - The Journal of biological chemistry AU - Baek, S J AU - Horowitz, J M AU - Eling, T E AD - Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/09/07/ PY - 2001 DA - 2001 Sep 07 SP - 33384 EP - 33392 VL - 276 IS - 36 SN - 0021-9258, 0021-9258 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - COUP Transcription Factor I KW - Chromatin KW - Cytokines KW - DNA-Binding Proteins KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - NR2F1 protein, human KW - Protein Isoforms KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - SP3 protein, human KW - Sp1 Transcription Factor KW - Transcription Factors KW - Sp3 Transcription Factor KW - 148710-94-5 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Chromatin -- metabolism KW - Transcription Factors -- metabolism KW - Cell Nucleus -- metabolism KW - Sequence Homology, Nucleic Acid KW - Humans KW - Transcription, Genetic KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Proteins -- metabolism KW - Genes, Reporter KW - Molecular Sequence Data KW - Sp1 Transcription Factor -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Plasmids -- metabolism KW - Glutathione Transferase -- metabolism KW - Precipitin Tests KW - Protein Binding KW - Gene Deletion KW - Cloning, Molecular KW - Binding Sites KW - Base Sequence KW - Transfection KW - Models, Genetic KW - Protein Structure, Tertiary KW - Mutation KW - Promoter Regions, Genetic KW - Cytokines -- genetics KW - Cytokines -- metabolism KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71144926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+cloning+and+characterization+of+human+nonsteroidal+anti-inflammatory+drug-activated+gene+promoter.+Basal+transcription+is+mediated+by+Sp1+and+Sp3.&rft.au=Baek%2C+S+J%3BHorowitz%2C+J+M%3BEling%2C+T+E&rft.aulast=Baek&rft.aufirst=S&rft.date=2001-09-07&rft.volume=276&rft.issue=36&rft.spage=33384&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF305420; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weight Loss from Maximum Body Weight among Middle-Aged and Older White Women and the Risk of Hip Fracture: The NHANES I Epidemiologic Follow-up Study AN - 954604884; 14326157 AB - Although weight loss increases bone loss and hip fracture risk in older women, little is known about the relation between weight loss in middle-aged women and subsequent hip fracture risk. The objective of this study was to determine the association between weight loss from reported maximum body weight in middle-aged and older women and the risk of hip fracture. Data were from a nationally representative sample of 2180 community-dwelling white women aged 50-74 years from the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey (NHEFS). In this prospective cohort study, incident hip fracture was ascertained during 22 years of follow-up. The adjusted relative risks associated with weight loss of 10% or more from maximum body weight were elevated for both middle-aged (RR 2.54; 95% CI 1.10-5.86) and older women (RR 2.04; 95% CI 1.37-3.04). For both ages combined, women in the lowest tertile of body mass index at maximum who lost 10% or more of weight had the highest risk of hip fracture (RR 2.37; 95% CI 1.32-4.27). Weight loss from maximum reported body weight in women aged 50-64 years and 65-74 years increased their risk of hip fracture, especially among those who were relatively thin. Weight loss of 10% or more from maximum weight among both middle-aged and older women is an important indicator of hip fracture risk. JF - Osteoporosis International AU - Langlois, JA AU - Mussolino, ME AU - Visser, M AU - Looker, A C AU - Harris, T AU - Madans, J AD - Epidemiology, Demography, and Biometry Program, National Institute on Aging, Bethesda; , US Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 763 EP - 768 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 12 IS - 9 SN - 0937-941X, 0937-941X KW - Physical Education Index; Calcium & Calcified Tissue Abstracts KW - Risk assessment KW - Age KW - Data processing KW - Weight control KW - Bones KW - Women KW - Fractures KW - Gerontology KW - Osteoporosis KW - Nutrition KW - Hips KW - Evaluation KW - Body weight KW - Weight KW - Risk factors KW - Bone loss KW - Body mass index KW - Hip KW - T 2020:Nutrition and Metabolism KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954604884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Global+differential+gene+expression+in+response+to+growth+temperature+alteration+in+group+A+Streptococcus.&rft.au=Smoot%2C+L+M%3BSmoot%2C+J+C%3BGraham%2C+M+R%3BSomerville%2C+G+A%3BSturdevant%2C+D+E%3BMigliaccio%2C+C+A%3BSylva%2C+G+L%3BMusser%2C+J+M&rft.aulast=Smoot&rft.aufirst=L&rft.date=2001-08-28&rft.volume=98&rft.issue=18&rft.spage=10416&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-05-07 N1 - SubjectsTermNotLitGenreText - Evaluation; Bones; Weight control; Weight; Women; Gerontology; Fractures; Nutrition; Hips; Risk assessment; Age; Data processing; Body weight; Risk factors; Bone loss; Osteoporosis; Body mass index; Hip DO - http://dx.doi.org/10.1007/s001980170053 ER - TY - JOUR T1 - Auditory dysfunction in Stickler syndrome. AN - 85366051; pmid-11556853 AB - To characterize the natural history and possible mechanisms of hearing loss in Stickler syndrome (OMIM 108300; or hereditary progressive arthro-ophthalmopathy) and to determine if the auditory phenotype is a useful discriminating feature for the differential diagnosis of this group of disorders.Multifamily study.Outpatient audiology and otolaryngology clinics at the Warren Grant Magnuson Clinical Center of the National Institutes of Health, Rockville, Md.Forty-six affected individuals from 29 different families segregating Stickler syndrome.Clinical audiologic and otolaryngological examinations were performed on all individuals, including pure-tone audiometry, speech audiometry, and middle ear immittance testing. Otoacoustic emissions, auditory brainstem response, infrared video electronystagmography, and temporal bone computed tomography were performed on a subset of participants.The hearing loss was most often sensorineural in adults, and approximately 28 (60%) of the 46 adult patients had 2 or more thresholds greater than the corresponding 95th percentile values for an age-matched, otologically normal population. The hearing loss most often affected high frequencies (4000-8000 Hz) and was generally no more progressive than that due to age-related hearing loss. Type A(D) tympanograms (classification using the Jerger model), indicating hypermobile middle ear systems, were observed in 21 (46%) of the 46 affected individuals. Computed tomography of the temporal bones revealed no inner ear malformations in 19 affected individuals.The hypermobile middle ear systems observed in ears with normal-appearing tympanic membranes represent a novel finding for Stickler syndrome and are likely to be a useful diagnostic feature for this disorder. The overall sensorineural hearing loss in type I Stickler syndrome is typically mild and not significantly progressive. It is less severe than that reported for types II and III Stickler syndrome linked to COL11A2 (OMIM 120290) and COL11A1 (OMIM 120280) mutations, respectively, or the closely related Marshall syndrome. This difference will be a useful discriminatory feature in the differential diagnosis of this group of disorders. JF - Archives of otolaryngology--head & neck surgery AU - Szymko-Bennett, Y M AU - Mastroianni, M A AU - Shotland, L I AU - Davis, J AU - Ondrey, F G AU - Balog, J Z AU - Rudy, S F AU - McCullagh, L AU - Levy, H P AU - Liberfarb, R M AU - Francomano, C A AU - Griffith, A J AD - Hearing Section, Neuro-Otology Branch, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA. Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 1061 EP - 1068 VL - 127 IS - 9 SN - 0886-4470, 0886-4470 KW - National Library of Medicine KW - Adolescent KW - Adult KW - Aged KW - *Audiometry, Pure-Tone KW - Child KW - Child, Preschool KW - *Cleft Palate KW - *Deafness: physiopathology KW - Disease Progression KW - Ear, Middle: physiopathology KW - *Face: abnormalities KW - Female KW - Humans KW - Infant KW - *Joint Instability KW - Male KW - Middle Aged KW - *Retina: abnormalities KW - Syndrome KW - *Vitreous Body: abnormalities UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+otolaryngology--head+%26+neck+surgery&rft.atitle=Auditory+dysfunction+in+Stickler+syndrome.&rft.au=Szymko-Bennett%2C+Y+M%3BMastroianni%2C+M+A%3BShotland%2C+L+I%3BDavis%2C+J%3BOndrey%2C+F+G%3BBalog%2C+J+Z%3BRudy%2C+S+F%3BMcCullagh%2C+L%3BLevy%2C+H+P%3BLiberfarb%2C+R+M%3BFrancomano%2C+C+A%3BGriffith%2C+A+J&rft.aulast=Szymko-Bennett&rft.aufirst=Y&rft.date=2001-09-01&rft.volume=127&rft.issue=9&rft.spage=1061&rft.isbn=&rft.btitle=&rft.title=Archives+of+otolaryngology--head+%26+neck+surgery&rft.issn=08864470&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Spike frequency decoding and autonomous activation of Ca2+-calmodulin-dependent protein kinase II in dorsal root ganglion neurons. AN - 85284102; pmid-11517259 AB - Autonomous activation of calcium-calmodulin kinase (CaMKII) has been proposed as a molecular mechanism for decoding Ca(2+) spike frequencies resulting from action potential firing, but this has not been investigated in intact neurons. This was studied in mouse DRG neurons in culture using confocal measurements of [Ca(2+)](i) and biochemical measurements of CaMKII autophosphorylation and autonomous activity. Using electrical stimulation at different frequencies, we find that CaMKII autonomous activity reached near maximal levels after approximately 45 impulses, regardless of firing frequency (1-10 Hz), and autonomous activity declined with prolonged stimulation. Frequency-dependent activation of CaMKII was limited to spike frequencies in the range of 0.1-1 Hz, despite marked increases in [Ca(2+)](i) at higher frequencies (1-30 Hz). The high levels of autonomous activity measured before stimulation and the relatively long duration of Ca(2+) spikes induced by action potentials ( approximately 300 msec) are consistent with the lower frequency range of action potential decoding by CaMKII. The high autonomous activity under basal conditions was associated with extracellular [Ca(2+)], independently from changes in [Ca(2+)](i), and unrelated to synaptic or spontaneous impulse activity. CaMKII autonomous activity in response to brief bursts of action potentials correlated better with the frequency of Ca(2+) transients than with the concentration of [Ca(2+)](i). In conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz in these neurons, but other mechanisms may be required to decode higher frequencies. Alternatively, CaMKII may mediate high-frequency responses in subcellular microdomains in which the enzyme is maintained at a low level of autonomous activity or the Ca(2+) transients have faster kinetics. JF - The Journal of Neuroscience AU - Eshete, F AU - Fields, R D AD - National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-4480, USA. PY - 2001 SP - 6694 EP - 6705 VL - 21 IS - 17 SN - 1529-2401, 1529-2401 KW - Support, U.S. Gov't, P.H.S. KW - Calcium KW - Diffusion Chambers, Culture KW - Enzyme Activation KW - Animal KW - Ca(2+)-Calmodulin Dependent Protein Kinase KW - Action Potentials KW - Ganglia, Spinal KW - Tetrodotoxin KW - Mice KW - Fluorescent Dyes KW - Electric Stimulation KW - Intracellular Fluid KW - Phosphorylation KW - Cells, Cultured KW - Neurons KW - Chelating Agents KW - Immunohistochemistry KW - Time Factors KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85284102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=Spike+frequency+decoding+and+autonomous+activation+of+Ca2%2B-calmodulin-dependent+protein+kinase+II+in+dorsal+root+ganglion+neurons.&rft.au=Eshete%2C+F%3BFields%2C+R+D&rft.aulast=Eshete&rft.aufirst=F&rft.date=2001-09-01&rft.volume=21&rft.issue=17&rft.spage=6694&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=15292401&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Noise reduction in oncology FDG PET images by iterative reconstruction: a quantitative assessment. AN - 85280280; pmid-11535719 AB - Tumor detection depends on the contrast between tumor activity and background activity and on the image noise in these 2 regions. The lower the image noise, the easier the tumor detection. Tumor activity contrast is determined by physiology. Noise, however, is affected by many factors, including the choice of reconstruction algorithm. Previous simulation and phantom measurements indicated that the ordered-subset expectation maximization (OSEM) algorithm may produce less noisy images than does the usual filtered backprojection (FBP) method, at equivalent resolution. To see if this prediction would hold in actual clinical situations, we quantified noise in clinical images reconstructed with both OSEM and FBP. METHODS: Three patients (2 with colon cancer, 1 with breast cancer) were imaged with FDG PET using a "gated replicate" technique that permitted accurate measurement of noise at each pixel. Each static image was acquired as a gated image sequence, using a pulse generator with a 1-s period, yielding 40 replicate images over the 10- to 15-min imaging time. The images were or were not precorrected for attenuation and were reconstructed with both FBP and OSEM at comparable resolution. From these data, images of pixel mean, SD, and signal-to-noise ratio (S/N) could be produced, reflecting only noise caused by the statistical fluctuations in the emission process. RESULTS: Noise did not vary greatly over each FBP image, even when image intensity varied greatly from one region to the next, causing S/N to be worse in low-activity regions than in high-activity regions. In contrast, OSEM had high noise in hot regions and low noise in cold regions. OSEM had a much better S/N than did FBP in cold regions of the image, such as the lungs (in the attenuation-corrected images), where improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in hotter areas such as the liver (averaging 25% improvement in the attenuation-corrected images). In very hot tumors, FBP actually produced higher S/Ns than did OSEM. CONCLUSION: We conclude that OSEM reconstruction can significantly reduce image noise, especially in relatively low-count regions. OSEM reconstruction failed to improve S/N in very hot tumors, in which S/N may already be adequate for tumor detection. JF - Journal of Nuclear Medicine AU - Riddell, C AU - Carson, R E AU - Carrasquillo, J A AU - Libutti, S K AU - Danforth, D N AU - Whatley, M AU - Bacharach, S L AD - National Institutes of Health, Bethesda, Maryland, USA. PY - 2001 SP - 1316 EP - 1323 VL - 42 IS - 9 SN - 0161-5505, 0161-5505 KW - Phantoms, Imaging KW - Comparative Study KW - Computer Simulation KW - Fludeoxyglucose F 18 KW - Human KW - Radiopharmaceuticals KW - Algorithms KW - Breast Neoplasms KW - Colonic Neoplasms KW - Image Processing, Computer-Assisted KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85280280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Nuclear+Medicine&rft.atitle=Noise+reduction+in+oncology+FDG+PET+images+by+iterative+reconstruction%3A+a+quantitative+assessment.&rft.au=Riddell%2C+C%3BCarson%2C+R+E%3BCarrasquillo%2C+J+A%3BLibutti%2C+S+K%3BDanforth%2C+D+N%3BWhatley%2C+M%3BBacharach%2C+S+L&rft.aulast=Riddell&rft.aufirst=C&rft.date=2001-09-01&rft.volume=42&rft.issue=9&rft.spage=1316&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine. AN - 72303757; 11725690 AB - To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer. JF - International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition AU - Kakizaki, S AU - Takagi, H AU - Fukusato, T AU - Toyoda, M AU - Horiguchi, N AU - Sato, K AU - Takayama, H AU - Nagamine, T AU - Mori, M AD - First Department of Internal Medicine, Gunma University School of Medecine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan. kakizaki@niehs.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 261 EP - 267 VL - 71 IS - 5 SN - 0300-9831, 0300-9831 KW - Alkylating Agents KW - 0 KW - Antioxidants KW - Transforming Growth Factor alpha KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - alpha-Tocopherol KW - H4N855PNZ1 KW - Index Medicus KW - Animals KW - Mice KW - Chemoprevention KW - Mice, Transgenic KW - Male KW - Diethylnitrosamine -- toxicity KW - Alkylating Agents -- therapeutic use KW - Antioxidants -- therapeutic use KW - Transforming Growth Factor alpha -- drug effects KW - Liver Neoplasms, Experimental -- chemically induced KW - Transforming Growth Factor alpha -- analysis KW - Liver Neoplasms, Experimental -- prevention & control KW - alpha-Tocopherol -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72303757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+for+vitamin+and+nutrition+research.+Internationale+Zeitschrift+fur+Vitamin-+und+Ernahrungsforschung.+Journal+international+de+vitaminologie+et+de+nutrition&rft.atitle=Effect+of+alpha-tocopherol+on+hepatocarcinogenesis+in+transforming+growth+factor-alpha+%28TGF-alpha%29+transgenic+mice+treated+with+diethylnitrosamine.&rft.au=Kakizaki%2C+S%3BTakagi%2C+H%3BFukusato%2C+T%3BToyoda%2C+M%3BHoriguchi%2C+N%3BSato%2C+K%3BTakayama%2C+H%3BNagamine%2C+T%3BMori%2C+M&rft.aulast=Kakizaki&rft.aufirst=S&rft.date=2001-09-01&rft.volume=71&rft.issue=5&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=International+journal+for+vitamin+and+nutrition+research.+Internationale+Zeitschrift+fur+Vitamin-+und+Ernahrungsforschung.+Journal+international+de+vitaminologie+et+de+nutrition&rft.issn=03009831&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-22 N1 - Date created - 2001-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chimeric fusion proteins--Pseudomonas exotoxin-based. AN - 72288397; 11717817 AB - Recombinant fusion toxins have several potential advantages over conventional immunotoxin chemical conjugates, including (i) a defined toxin-ligand junction; (ii) efficient and relatively inexpensive production in large scale from bacteria; (iii) shorter plasma half-lives which might avoid diffuse endothelial damage which leads to vascular leak syndrome (VLS); and (iv) ability to genetically engineer mutations in the recombinant toxin to increase its potency or lower its non-specific toxicity. Two major varieties of recombinant fusion toxins include growth factor fusion toxins, containing a growth factor fused to truncated toxin, and recombinant immunotoxins, containing the variable fragments of an antibody fused to truncated toxin. In either case the ligand is used to bind selectively to tumor cells while the toxin kills the target cell following internalization. The bacterial toxins Pseudomonas exotoxin and diphtheria toxin are most often used for making recombinant fusion toxins. This review will focus on several agents containing truncated Pseudomonas exotoxin, which are undergoing preclinical and clinical development. JF - Current opinion in investigational drugs (London, England : 2000) AU - Kreitman, R J AD - National Cancer Institute, NIH, Clinical Immunotherapy Section, Laboratory of Molecular Biology, Division of Cancer Biology, 9000 Rockville Pike, Building 37, Room 4B-27, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1282 EP - 1293 VL - 2 IS - 9 SN - 1472-4472, 1472-4472 KW - Antineoplastic Agents KW - 0 KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Leukemia -- drug therapy KW - Animals KW - Humans KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- pharmacology KW - Leukemia, B-Cell -- drug therapy KW - Neoplasms -- drug therapy KW - Recombinant Fusion Proteins -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72288397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.atitle=Chimeric+fusion+proteins--Pseudomonas+exotoxin-based.&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2001-09-01&rft.volume=2&rft.issue=9&rft.spage=1282&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.issn=14724472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-08 N1 - Date created - 2001-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteomic approaches within the NCI early detection research network for the discovery and identification of cancer biomarkers. AN - 72278400; 11708463 AB - In the postgenome era, proteomics provides a powerful approach for the analysis of normal and transformed cell functions, for the identification of disease-specific targets, and for uncovering novel endpoints for the evaluation of chemoprevention agents and drug toxicity. Unfortunately, the genomic information that has greatly expounded the genetic basis of cancer does not allow an accurate prediction of what is actually occurring at the protein level within a given cell type at any given time. The gene expression program of a given cell is affected by numerous factors in the in vivo environment resulting from tissue complexity and organ system orchestration, with cells acting in concert with each other and responding to changes in their microenvironment. Repositories of genomic information can be considered master "inventory lists" of genes and their maps, which need to be supplemented with protein-derived information. The National Cancer Institute's Early Detection Research Network is employing proteomics, or "protein walking", in the discovery and evaluation of biomarkers for cancer detection and for the identification of high-risk subjects. Armed with microdissection techniques, including the use of Laser Capture Microdissection (LCM) to procure pure populations of cells directly from human tissue, the Network is facilitating the development of technologies that can overcome the problem of tissue heterogeneity and address the need to identify markers in easily accessible biological fluids. Proteomic approaches complement plasma-based assays of circulating DNA for cancer detection and risk assessment. LCM, coupled with downstream proteomics applications, such as two-dimensional polyacrylamide gel electrophoresis and SELDI (surface enhanced laser desorption ionization) separation followed by mass spectrometry (MS) analysis, may greatly facilitate the characterization and identification of protein expression changes that track normal and disease phenotypes. We highlight recent work from Network investigators to demonstrate the potential of proteomics to identify proteins present in cancer tissues and body fluids that are relevant for cancer screening. JF - Annals of the New York Academy of Sciences AU - Verma, M AU - Wright, G L AU - Hanash, S M AU - Gopal-Srivastava, R AU - Srivastava, S AD - Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 103 EP - 115 VL - 945 SN - 0077-8923, 0077-8923 KW - Biomarkers, Tumor KW - 0 KW - Proteome KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Computational Biology KW - Genome KW - Biomarkers, Tumor -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72278400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Proteomic+approaches+within+the+NCI+early+detection+research+network+for+the+discovery+and+identification+of+cancer+biomarkers.&rft.au=Verma%2C+M%3BWright%2C+G+L%3BHanash%2C+S+M%3BGopal-Srivastava%2C+R%3BSrivastava%2C+S&rft.aulast=Verma&rft.aufirst=M&rft.date=2001-09-01&rft.volume=945&rft.issue=&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validity study of self-reported pesticide exposure among orchardists. AN - 72250445; 11687909 AB - Self-reported work histories are often the only means of estimating occupational exposures in epidemiologic research. The objective of this study was to examine the accuracy of recall of historical pesticide use among orchardists. All 185 orchardists in this study had participated previously in a cohort study of men occupationally exposed to pesticides. In that study (1972 to 1976), subjects were interviewed annually and asked to list pesticides used since the last interview. In 1997, 265 of the 440 presumed-living orchardists from the original cohort were successfully recontacted and asked to complete a detailed questionnaire concerning their lifetime use of pesticides; 185 (69.8% of farmers successfully contacted) agreed. Considering the 1972-1976 data as the standard, sensitivity and specificity of recall were calculated for certain pesticides and pesticide categories. Sensitivity of recall was good to excellent (0.6-0.9) for the broad categories of insecticides, herbicides, and fungicides, for heavily used chemical classes, such as organophosphates and organochlorines, and for commonly used pesticides; it was lower and more variable (0.1-0.6) for specific pesticides. Recall specificity was greatest (0.7-0.9) for the least used pesticides and chemical classes, such as dithiocarbamates and manganese-containing pesticides, and was generally modest for the rest (0.5-0.6). There was no evidence of selection bias between study participants and nonparticipants. In conclusion, recall accuracy was good for commonly used pesticides and pesticide categories. This level of recall accuracy is probably adequate for epidemiologic analyses of broad categories of pesticides, but is a limitation for detecting more specific associations. JF - Journal of exposure analysis and environmental epidemiology AU - Engel, L S AU - Seixas, N S AU - Keifer, M C AU - Longstreth, W T AU - Checkoway, H AD - Department of Epidemiology, University of Washington, Seattle, Washington, USA. engell@mail.nih.gov PY - 2001 SP - 359 EP - 368 VL - 11 IS - 5 SN - 1053-4245, 1053-4245 KW - Pesticides KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Epidemiologic Studies KW - Aged, 80 and over KW - Humans KW - Cohort Studies KW - Aged KW - Middle Aged KW - Bias (Epidemiology) KW - Male KW - Pesticides -- analysis KW - Occupational Exposure KW - Agriculture KW - Mental Recall KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72250445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.atitle=Validity+study+of+self-reported+pesticide+exposure+among+orchardists.&rft.au=Engel%2C+L+S%3BSeixas%2C+N+S%3BKeifer%2C+M+C%3BLongstreth%2C+W+T%3BCheckoway%2C+H&rft.aulast=Engel&rft.aufirst=L&rft.date=2001-09-01&rft.volume=11&rft.issue=5&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.issn=10534245&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progress in the application of DNA microarrays. AN - 72219235; 11673116 AB - Microarray technology has been applied to a variety of different fields to address fundamental research questions. The use of microarrays, or DNA chips, to study the gene expression profiles of biologic samples began in 1995. Since that time, the fundamental concepts behind the chip, the technology required for making and using these chips, and the multitude of statistical tools for analyzing the data have been extensively reviewed. For this reason, the focus of this review will be not on the technology itself but on the application of microarrays as a research tool and the future challenges of the field. JF - Environmental health perspectives AU - Lobenhofer, E K AU - Bushel, P R AU - Afshari, C A AU - Hamadeh, H K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 881 EP - 891 VL - 109 IS - 9 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Medical Informatics KW - Humans KW - Infection KW - Research Design KW - Neoplasms -- genetics KW - Oligonucleotide Array Sequence Analysis -- trends KW - Gene Expression Profiling KW - Environmental Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72219235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Progress+in+the+application+of+DNA+microarrays.&rft.au=Lobenhofer%2C+E+K%3BBushel%2C+P+R%3BAfshari%2C+C+A%3BHamadeh%2C+H+K&rft.aulast=Lobenhofer&rft.aufirst=E&rft.date=2001-09-01&rft.volume=109&rft.issue=9&rft.spage=881&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 2000 Apr 15;60(8):2232-8 [10786689] Carcinogenesis. 2000 May;21(5):1023-9 [10783328] Int J Cancer. 2000 Jun 1;86(5):731-6 [10797298] Med Res Rev. 2000 May;20(3):189-96 [10797463] J Biol Chem. 2000 May 12;275(19):14084-94 [10799483] J Biol Chem. 2000 May 12;275(19):14632-41 [10799550] Nat Biotechnol. 2000 May;18(5):561-4 [10802632] Nat Genet. 2000 May;25(1):96-101 [10802665] J Cancer Res Clin Oncol. 2000 May;126(5):271-9 [10815762] Radiat Res. 2000 May;153(5 Pt 2):679-84 [10790292] Mol Reprod Dev. 2000 Jun;56(2):113-23 [10813842] Ann N Y Acad Sci. 2000 Apr;906:39-43 [10818594] Mol Carcinog. 2000 May;28(1):12-22 [10820484] Cancer Res. 2000 May 15;60(10):2716-22 [10825146] J Immunol Methods. 2000 May 26;239(1-2):167-79 [10821957] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5773-8 [10811900] Clin Cancer Res. 1999 Aug;5(8):1966-75 [10473073] Nat Genet. 1999 Sep;23(1):41-6 [10471496] Cancer Res. 1999 Sep 1;59(17):4228-32 [10485462] Am J Pathol. 1999 Sep;155(3):739-52 [10487832] J Mol Biol. 1999 Sep 17;292(2):251-62 [10493873] Cancer Res. 1999 Oct 1;59(19):4759-60 [10519378] Science. 1999 Oct 15;286(5439):531-7 [10521349] FEBS Lett. 2000 Aug 25;480(1):2-16 [10967322] FEBS Lett. 2000 Aug 25;480(1):17-24 [10967323] Am J Pathol. 2000 Sep;157(3):787-94 [10980118] J Natl Cancer Inst. 1999 Mar 3;91(5):400-1 [10070933] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2907-12 [10077610] Gene. 1999 Mar 18;229(1-2):101-8 [10095109] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10748-52 [1438272] Science. 1994 Oct 7;266(5182):66-71 [7545954] Am J Clin Pathol. 1994 Oct;102(4):406-14 [7524299] Neurotoxicology. 1995 Spring;16(1):133-8 [7603633] Science. 1995 Oct 20;270(5235):467-70 [7569999] Gene. 1995 Oct 27;164(2):219-27 [7590334] Biotechniques. 1996 Apr;20(4):584-91 [8800675] Annu Rev Biochem. 1996;65:337-65 [8811183] Nat Genet. 1996 Dec;14(4):457-60 [8944026] CA Cancer J Clin. 1997 Jan-Feb;47(1):28-51 [8996077] Int J Cancer. 1997 Feb 20;74(1):35-44 [9036867] Cancer Res. 1997 Aug 1;57(15):3294-9 [9242463] Curr Opin Hematol. 1996 Sep;3(5):379-84 [9372105] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5984-8 [10811893] Science. 2000 Jun 2;288(5471):1635-40 [10834841] J Biol Chem. 2000 Jun 9;275(23):17249-55 [10748181] J Natl Cancer Inst. 2000 Jun 7;92(11):937-9 [10841830] Res Commun Mol Pathol Pharmacol. 1999;105(1-2):77-86 [10850371] Nature. 2000 Jun 8;405(6787):701-4 [10864329] Cancer Res. 2000 Jun 15;60(12):3155-9 [10866304] Gene. 2000 Jun 13;251(1):45-53 [10863095] Electrophoresis. 2000 May;21(9):1823-31 [10870968] Biochem Biophys Res Commun. 2000 Jul 5;273(2):675-80 [10873663] Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7957-62 [10884426] Nat Genet. 2000 Jul;25(3):333-7 [10888885] J Biol Chem. 2000 Jun 30;275(26):19676-84 [10783395] Am J Respir Cell Mol Biol. 2000 Sep;23(3):355-63 [10970827] J Biol Chem. 2000 Sep 8;275(36):27874-82 [10882716] Biochem Biophys Res Commun. 2000 Sep 7;275(3):731-8 [10973791] Immunity. 2000 Aug;13(2):199-212 [10981963] Genome Res. 2000 Sep;10(9):1393-402 [10984457] Biotechniques. 2000 Sep;29(3):530-6 [10997267] Biotechniques. 2000 Sep;29(3):548-50, 552-4, 556 passim [10997270] Radiat Res. 2000 Sep;154(3):342-6 [11012342] Biochem Pharmacol. 2000 Oct 15;60(8):1129-42 [11007951] Nature. 2000 Sep 21;407(6802):390-5 [11014196] Microb Comp Genomics. 1998;3(1):1-11 [11013707] Cancer Res. 2000 Sep 15;60(18):5007-11 [11016619] Clin Chem. 2000 Oct;46(10):1555-61 [11017932] Yeast. 2000 Sep 30;17(3):211-7 [11025531] Cancer Res. 2000 Oct 1;60(19):5323-8 [11034064] Cancer Res. 2000 Oct 1;60(19):5340-4 [11034067] J Biol Chem. 2000 Oct 13;275(41):32310-6 [10922376] Toxicol Sci. 2000 Dec;58(2):399-415 [11099651] Microbes Infect. 2000 Oct;2(12):1479-87 [11099934] J Biol Chem. 2000 Dec 8;275(49):38524-31 [10984481] Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13847-52 [11087813] Nucleic Acids Res. 2001 Mar 1;29(5):E29 [11222780] J Comput Biol. 2000;7(6):819-37 [11382364] Acta Neuropathol. 1977 Nov 28;40(3):259-68 [602688] Life Sci. 1983 Sep 5;33(10):1001-6 [6310286] Toxicol Appl Pharmacol. 1988 Oct;96(1):14-23 [3188018] Science. 1990 Feb 2;247(4942):568-71 [2300817] Nature. 1990 May 31;345(6274):458-60 [2342578] Nature. 1991 Apr 18;350(6319):569-73 [1708110] Cancer Res. 1999 Oct 15;59(20):5119-22 [10537285] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12833-8 [10536008] J Natl Cancer Inst. 1999 Oct 20;91(20):1758-64 [10528027] Cancer Res. 1999 Nov 1;59(21):5403-7 [10554005] Cancer Res. 1999 Nov 1;59(21):5464-70 [10554019] Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13264-9 [10557309] Cancer Res. 1999 Nov 15;59(22):5656-61 [10582678] Nature. 1999 Nov 25;402(6760):418-21 [10586882] Circ Res. 1999 Dec 3-17;85(12):1118-23 [10590237] Science. 1999 Dec 10;286(5447):2179-84 [10591654] Curr Opin Genet Dev. 1999 Dec;9(6):715-22 [10607618] Virology. 2000 Jan 5;266(1):8-16 [10612655] Yeast. 2000 Jan 15;16(1):23-33 [10620772] Anticancer Res. 1999 Sep-Oct;19(5B):3873-87 [10628326] Mol Microbiol. 2000 Jan;35(1):6-14 [10632873] J Biol Chem. 2000 Jan 28;275(4):2777-85 [10644742] Science. 2000 Feb 4;287(5454):873-80 [10657304] Nature. 2000 Feb 3;403(6769):503-11 [10676951] Parassitologia. 1999 Sep;41(1-3):69-75 [10697835] Nat Genet. 2000 Mar;24(3):227-35 [10700174] Nat Genet. 2000 Mar;24(3):236-44 [10700175] Cancer Res. 2000 Feb 15;60(4):1062-9 [10706125] Oncogene. 2000 Feb 17;19(7):916-23 [10702800] Laryngoscope. 2000 Mar;110(3 Pt 1):374-81 [10718422] Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2456-61 [10716982] Toxicol Lett. 2000 Mar 15;112-113:473-7 [10720768] Cancer Res. 2000 Mar 1;60(5):1353-60 [10728698] Arch Biochem Biophys. 2000 Apr 1;376(1):66-73 [10729191] Br J Cancer. 2000 Mar;82(6):1239-45 [10735512] Cancer Res. 2000 Mar 15;60(6):1677-82 [10749139] Nat Biotechnol. 2000 Apr;18(4):457-9 [10748532] J Biol Chem. 2000 Apr 14;275(15):11181-90 [10753925] J Virol. 2000 May;74(9):4174-82 [10756030] In Vivo. 2000 Jan-Feb;14(1):173-82 [10757075] Cancer Res. 2000 Apr 1;60(7):1824-9 [10766166] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13057-62 [9371799] Genes Chromosomes Cancer. 1997 Dec;20(4):399-407 [9408757] Nat Biotechnol. 1997 Dec;15(13):1359-67 [9415887] CA Cancer J Clin. 1998 Mar-Apr;48(2):83-107 [9522824] Nucleic Acids Res. 1998 Jun 15;26(12):3059-65 [9611255] Nat Med. 1998 Jul;4(7):844-7 [9662379] Genomics. 1998 Jun 15;50(3):331-40 [9676427] Science. 1998 Jul 24;281(5376):533-8 [9677190] Mol Cell. 1998 Jul;2(1):65-73 [9702192] Nat Genet. 1998 Sep;20(1):19-23 [9731524] Biotechniques. 1998 Sep;25(3):504-8, 510, 512, passim [9762448] Nat Genet. 1998 Oct;20(2):207-11 [9771718] Nucleic Acids Res. 1998 Nov 1;26(21):4975-82 [9776762] Nat Med. 1998 Nov;4(11):1293-301 [9809554] Cancer Res. 1998 Nov 15;58(22):5009-13 [9823299] Cell. 1998 Nov 25;95(5):717-28 [9845373] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Genome Res. 1998 Nov;8(11):1142-53 [9847078] Clin Cancer Res. 1998 Dec;4(12):3045-50 [9865919] Nat Genet. 1999 Jan;21(1 Suppl):10-4 [9915494] Nat Genet. 1999 Jan;21(1 Suppl):15-9 [9915495] Cancer Res. 1999 Feb 15;59(4):803-6 [10029066] Nucleic Acids Res. 1999 Mar 15;27(6):1517-23 [10037815] FEBS Lett. 2000 Mar 24;470(2):156-60 [10734226] Oncogene. 2000 Mar 16;19(12):1519-28 [10734311] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3364-9 [10725359] Mol Carcinog. 1999 Mar;24(3):153-9 [10204799] Am J Pathol. 1999 Apr;154(4):981-6 [10233835] Int J Cancer. 1999 May 31;81(5):688-94 [10328217] Oncogene. 1999 Apr 29;18(17):2711-7 [10348345] Science. 1999 May 28;284(5419):1520-3 [10348738] Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6745-50 [10359783] Cell. 1999 May 28;97(5):575-86 [10367887] J Exp Med. 1999 Jun 21;189(12):1939-46 [10377189] Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7382-7 [10377423] Oncogene. 1999 Jun 17;18(24):3666-72 [10380890] Nat Biotechnol. 1999 Jun;17(6):555-61 [10385319] Blood. 1999 Jul 15;94(2):411-6 [10397707] Science. 1999 Jul 9;285(5425):251-4 [10398601] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9212-7 [10430922] Genes Chromosomes Cancer. 1999 Sep;26(1):70-9 [10441008] Science. 1999 Aug 27;285(5432):1390-3 [10464095] Br J Cancer. 2000 Jul;83(2):164-70 [10901365] Br J Cancer. 2000 Jul;83(2):246-51 [10901378] Exp Cell Res. 2000 Aug 1;258(2):270-8 [10896778] Mol Carcinog. 2000 Jun;28(2):119-27 [10900469] Oncogene. 2000 Jun 29;19(28):3220-4 [10918578] Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9127-32 [10922068] J Natl Cancer Inst. 2000 Aug 2;92(15):1252-9 [10922410] Cell. 2000 Jul 7;102(1):109-26 [10929718] J Cancer Res Clin Oncol. 2000 Jul;126(7):400-6 [10929762] Neoplasia. 1999 Aug;1(3):262-75 [10935481] Cancer Res. 2000 Aug 1;60(15):4161-6 [10945624] Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9659-64 [10931941] Lab Invest. 2000 Aug;80(8):1259-68 [10950117] Nature. 2000 Aug 3;406(6795):532-5 [10952316] Nature. 2000 Aug 3;406(6795):536-40 [10952317] Nature. 2000 Aug 17;406(6797):747-52 [10963602] Oncogene. 2000 Aug 24;19(36):4125-33 [10962573] Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9834-9 [10963655] Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10209-13 [10954754] Cancer Res. 2000 Aug 15;60(16):4519-25 [10969801] Cancer Res. 2000 Aug 15;60(16):4561-72 [10969808] J Biochem Mol Toxicol. 2000;14(5):283-90 [10970000] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis. AN - 72217169; 11665847 AB - Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Mingchao AU - Devereux, T R AU - Stockton, P AU - Sun, K AU - Sills, R C AU - Clayton, N AU - Portier, M AU - Flake, G AD - Laboratory of Experimental Pathology and NIEHS, NIH, Research Triangle Park, NC 27709, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 237 EP - 246 VL - 53 IS - 4 SN - 0940-2993, 0940-2993 KW - CTNNB1 protein, human KW - 0 KW - Cadherins KW - Cytoskeletal Proteins KW - DNA Primers KW - DNA, Neoplasm KW - Trans-Activators KW - Tumor Suppressor Protein p53 KW - beta Catenin KW - Index Medicus KW - Precancerous Conditions KW - Micromanipulation KW - Humans KW - Metaplasia -- metabolism KW - Aged KW - DNA, Neoplasm -- analysis KW - Helicobacter pylori -- pathogenicity KW - Cytoskeletal Proteins -- analysis KW - Gastric Mucosa -- pathology KW - Polymerase Chain Reaction KW - Helicobacter pylori -- isolation & purification KW - Gastric Mucosa -- chemistry KW - Adult KW - Metaplasia -- pathology KW - Middle Aged KW - Cytoskeletal Proteins -- metabolism KW - DNA Primers -- analysis KW - Methylation KW - Male KW - Immunoenzyme Techniques KW - Dissection -- methods KW - Gastric Mucosa -- metabolism KW - Stomach Neoplasms -- pathology KW - Adenocarcinoma -- metabolism KW - Tumor Suppressor Protein p53 -- analysis KW - Cadherins -- analysis KW - Stomach Neoplasms -- metabolism KW - Cadherins -- metabolism KW - Adenocarcinoma -- chemistry KW - Tumor Suppressor Protein p53 -- metabolism KW - Stomach Neoplasms -- chemistry KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72217169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=Loss+of+E-cadherin+expression+in+gastric+intestinal+metaplasia+and+later+stage+p53+altered+expression+in+gastric+carcinogenesis.&rft.au=Mingchao%3BDevereux%2C+T+R%3BStockton%2C+P%3BSun%2C+K%3BSills%2C+R+C%3BClayton%2C+N%3BPortier%2C+M%3BFlake%2C+G&rft.aulast=Mingchao&rft.aufirst=&rft.date=2001-09-01&rft.volume=53&rft.issue=4&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=09402993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-28 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin and escalating doses of paclitaxel and epirubicin in advanced ovarian cancer. A phase I study. AN - 72190223; 11592349 AB - The combination of paclitaxel and cisplatin is considered the standard regimen for advanced ovarian cancer (AOC). A meta-analysis has shown that the incorporation of anthracyclines into first-line chemotherapy might improve long-term survival by 7-10%. We designed a phase I-II study in patients with AOC using a combination of a fixed dose of cisplatin with paclitaxel and epirubicin both given at escalating doses every 3 weeks. The objectives of this study were to determine both the maximum tolerated dose (MTD) and the antitumor activity of this combination. Six different dose levels were planned. The starting doses were cisplatin 75 mg/m2, paclitaxel 140 mg/m2, and epirubicin 50 mg/m2. The doses of paclitaxel were escalated in 20-mg/m2 increments, alternating with 20-mg/m2 increments of epirubicin. Ten patients with AOC entered the phase I study. Three patients each were enrolled at level I and level II and four patients at level III, and at each level, 15 courses were administered. Patients received a median of five courses. Nonhematological toxicity was generally mild, except for grade 3 mucositis in one course at levels II and III, and grade 3 vomiting in one course at levels I and III. Hematological toxicities were grade 3-4 neutropenia in 60%, 47% and 60% of courses at levels I, II and III, respectively, and grade 3 anemia in one course at level III. At level III two of four patients developed a dose-limiting toxicity which was grade 4 neutropenia lasting more than 1 week. The MTD was reached at level II with cisplatin 75 mg/m2, paclitaxel 160 mg/m2, and epirubicin 50 mg/m2. The phase II part of the study is currently ongoing. JF - Cancer chemotherapy and pharmacology AU - Nardi, M AU - De Marco, S AU - Fabi, A AU - Aloe, A AU - Magnani, E AU - Pacetti, U AU - Carlini, P AU - Ruggeri, E M AU - Cognetti, F AD - Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. sdemarco@medscape.com Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 255 EP - 258 VL - 48 IS - 3 SN - 0344-5704, 0344-5704 KW - Epirubicin KW - 3Z8479ZZ5X KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Infusions, Intravenous KW - Neoplasm Staging KW - Humans KW - Aged KW - Neutropenia -- chemically induced KW - Cisplatin -- administration & dosage KW - Nausea -- chemically induced KW - Treatment Outcome KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Epirubicin -- administration & dosage KW - Maximum Tolerated Dose KW - Female KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72190223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Cisplatin+and+escalating+doses+of+paclitaxel+and+epirubicin+in+advanced+ovarian+cancer.+A+phase+I+study.&rft.au=Nardi%2C+M%3BDe+Marco%2C+S%3BFabi%2C+A%3BAloe%2C+A%3BMagnani%2C+E%3BPacetti%2C+U%3BCarlini%2C+P%3BRuggeri%2C+E+M%3BCognetti%2C+F&rft.aulast=Nardi&rft.aufirst=M&rft.date=2001-09-01&rft.volume=48&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of probenecid on ventricular cerebrospinal fluid methotrexate pharmacokinetics after intralumbar administration in nonhuman primates. AN - 72190118; 11592346 AB - Intrathecal methotrexate (MTX) achieves high concentrations in the cerebrospinal fluid (CSF) following intralumbar administration. However, peak ventricular CSF MTX concentrations are highly variable and are < 10% of those achieved with intraventricular dosing. The objectives of this study were to evaluate the effect of intralumbar and intravenous probenecid on ventricular CSF MTX concentrations after intralumbar administration of MTX, and to compare the pharmacokinetics of MTX after intralumbar and intraventricular administration. Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received 0.5 mg intraventricular (lateral ventricle) MTX, or 0.5 mg intralumbar MTX with and without intralumbar or intravenous probenecid. Animals were kept prone for 1 h after MTX administration, and ventricular CSF was sampled up to 48 h from a fourth ventricular Ommaya reservoir. MTX concentrations were measured using the dihydrofolate reductase enzyme inhibition assay. Area under the ventricular CSF MTX concentration-time curve (AUC) was used as a measure of MTX exposure. Peak ventricular CSF MTX concentrations and AUCs were highly variable after intralumbar MTX administration. Ventricular CSF MTX AUCs increased by a mean of 3.2-fold after the addition of intralumbar probenecid. Intravenous administration of probenecid did not result in an increase in ventricular CSF MTX AUCs. Asymptomatic pleocytosis was observed in all animals after intralumbar probenecid administration. Ventricular CSF MTX concentrations and AUCs were less variable after intraventricular administration of MTX. The administration of intralumbar but not intravenous probenecid increases the ventricular CSF MTX exposure after intralumbar MTX administration. JF - Cancer chemotherapy and pharmacology AU - Salzer, W AU - Widemann, B AU - McCully, C AU - Adamson, P C AU - Balis, F M AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA. wanda.salzer@keesler.af.mil Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 235 EP - 240 VL - 48 IS - 3 SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Uricosuric Agents KW - Probenecid KW - PO572Z7917 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Lumbosacral Region KW - Infusions, Intravenous KW - Area Under Curve KW - Injections, Spinal KW - Cerebral Ventricles -- metabolism KW - Toxicity Tests KW - Macaca mulatta KW - Drug Administration Routes KW - Injections, Intraventricular KW - Methotrexate -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- cerebrospinal fluid KW - Methotrexate -- cerebrospinal fluid KW - Cerebrospinal Fluid -- metabolism KW - Probenecid -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Uricosuric Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72190118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Effect+of+probenecid+on+ventricular+cerebrospinal+fluid+methotrexate+pharmacokinetics+after+intralumbar+administration+in+nonhuman+primates.&rft.au=Salzer%2C+W%3BWidemann%2C+B%3BMcCully%2C+C%3BAdamson%2C+P+C%3BBalis%2C+F+M&rft.aulast=Salzer&rft.aufirst=W&rft.date=2001-09-01&rft.volume=48&rft.issue=3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I and pharmacologic study of 9-aminocamptothecin administered as a 120-h infusion weekly to adult cancer patients. AN - 72186475; 11592343 AB - To define the toxicity profile and the recommended phase II doses of 9-aminocamptothecin (9-AC) administered as a weekly 120-h infusion. 9-AC was administered over 120 h weekly to 55 adult cancer patients with solid tumors over doses ranging from 0.41 to 0.77 mg/m2 per day in a phase I and pharmacologic study. 9-AC formulated in dimethylacetamide/polyethylene glycol (DMA) was administered on a 3 of 4-week schedule, and the newer colloidal dispersion (CD) formulation was given on a 2 of 3-week schedule. Overall, 193 courses of therapy were administered over 122 dose levels. On the 3 of 4-week schedule, 9-AC DMA infused at > or = 0.6 mg/m2 per day for 120 h weekly produced dose-limiting neutropenia, thrombocytopenia, and diarrhea, or resulted in 1-2-week treatment delays. Shortening treatments to 2 of 3 weeks resulted in dose-limiting neutropenia and fatigue at infusion rates > 0.72 mg/m2 per day. The ratio of 9-AC lactone to total (carboxylate + lactone) drug plasma concentrations at steady-state was 0.15 +/- 0.07. Clinical toxicities and drug pharmacokinetics were not substantially different between the DMA and CD formulations. One objective response was observed in a patient with bladder cancer and minor responses were observed in patients with lung and colon cancers. Plasma area under the concentration versus time curve for 9-AC lactone modestly correlated with the degree of thrombocytopenia (r=0.51) using a sigmoid Emax pharmacodynamic model. The recommended phase II dose for the 9-AC DMA formulation is 0.48 mg/m2 per h over 120 h for 3 of 4 weeks and for the 9-AC CD formulation is 0.6 mg/m2 per day over 120 h for 2 of 3 weeks. Both regimens were well tolerated and feasible to administer. JF - Cancer chemotherapy and pharmacology AU - Thomas, R R AU - Dahut, W AU - Harold, N AU - Grem, J L AU - Monahan, B P AU - Liang, M AU - Band, R A AU - Cottrell, J AU - Llorens, V AU - Smith, J A AU - Corse, W AU - Arbuck, S G AU - Wright, J AU - Chen, A P AU - Shapiro, J D AU - Hamilton, J M AU - Allegra, C J AU - Takimoto, C H AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20889, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 215 EP - 222 VL - 48 IS - 3 SN - 0344-5704, 0344-5704 KW - Antineoplastic Agents KW - 0 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Hematologic Tests KW - Infusions, Intravenous KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Metabolic Clearance Rate KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Platelet Count KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- administration & dosage KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72186475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=A+phase+I+and+pharmacologic+study+of+9-aminocamptothecin+administered+as+a+120-h+infusion+weekly+to+adult+cancer+patients.&rft.au=Thomas%2C+R+R%3BDahut%2C+W%3BHarold%2C+N%3BGrem%2C+J+L%3BMonahan%2C+B+P%3BLiang%2C+M%3BBand%2C+R+A%3BCottrell%2C+J%3BLlorens%2C+V%3BSmith%2C+J+A%3BCorse%2C+W%3BArbuck%2C+S+G%3BWright%2C+J%3BChen%2C+A+P%3BShapiro%2C+J+D%3BHamilton%2C+J+M%3BAllegra%2C+C+J%3BTakimoto%2C+C+H&rft.aulast=Thomas&rft.aufirst=R&rft.date=2001-09-01&rft.volume=48&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A. AN - 72183959; 11591815 AB - Integrin receptor activation is an important regulatory mechanism for cell-substrate and cell-cell adhesion. In this study, we explore a signaling pathway activated by mAb 12G10, an antibody that can activate beta(1) integrins and induce integrin-mediated cell-cell and cell-substrate adhesion. We have found that the cAMP-dependent protein kinase (PKA) is required for both mAb 12G10-induced cell-cell and cell-substrate adhesion of HT-1080 cells. Binding of mAb 12G10 to beta(1) integrins stimulates an increase in intracellular cAMP levels and PKA activity, and a concomitant shift in the localization of the PKA type II regulatory subunits from the cytoplasm to areas where integrins expressing the 12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a combination of clustering beta(1) integrins and elevating PKA activity with Sp-adenosine-3',5'-cyclic monophosphorothioate or forskolin. We also show that two processes required for HT-1080 cell-cell adhesion, integrin clustering and F-actin polymerization are both dependent on PKA. Taken together, our data suggest that PKA plays a key role in the signaling pathway, resulting from activation of beta(1) integrins, and that this enzyme may be required for upregulation of cell-substrate and cell-cell adhesion. JF - Journal of cell science AU - Whittard, J D AU - Akiyama, S K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 3265 EP - 3272 VL - 114 SN - 0021-9533, 0021-9533 KW - Actins KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD29 KW - Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit KW - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit KW - PRKAR2A protein, human KW - PRKAR2B protein, human KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinase Type II KW - EC 2.7.11.11 KW - Cyclic AMP-Dependent Protein Kinases KW - Index Medicus KW - Fibrosarcoma -- metabolism KW - Tumor Cells, Cultured -- metabolism KW - Cytoplasm -- metabolism KW - Humans KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Cell Adhesion -- physiology KW - Antigens, CD29 -- metabolism KW - Antibodies, Monoclonal -- metabolism KW - Antigens, CD29 -- drug effects KW - Cyclic AMP-Dependent Protein Kinases -- drug effects KW - Cyclic AMP -- metabolism KW - Cyclic AMP -- agonists KW - Actins -- drug effects KW - Actins -- metabolism KW - Antibodies, Monoclonal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72183959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=Positive+regulation+of+cell-cell+and+cell-substrate+adhesion+by+protein+kinase+A.&rft.au=Whittard%2C+J+D%3BAkiyama%2C+S+K&rft.aulast=Whittard&rft.aufirst=J&rft.date=2001-09-01&rft.volume=114&rft.issue=&rft.spage=3265&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-19 N1 - Date created - 2001-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced cardiomyopathy. AN - 72180925; 11589785 AB - The major limiting factor in long-term administration of doxorubicin is the development of cumulative dose-dependent cardiomyopathy and congestive heart failure. Although several mechanisms have been suggested to explain the exact cause of doxorubicin-induced cardiomyopathy, the role of the vascular endothelium-derived vasoactive mediators in the pathophysiology of this toxic effect is still unknown. Accordingly, the present study has been initiated to investigate whether the changes in plasma level of endothelin-1 and nitric oxide along with cardiac nitric oxide are associated with the development of doxorubicin-induced cardiomyopathy. Doxorubicin was injected with a single dose of 5 mg/kg and every other day with a dose of 5 mg/kg, intraperitoneally, to have four cumulative doses of, 10, 15, 20 and 25 mg/kg in five separate groups of male rats. An additional group receiving a single dose of 20 mg/kg and one receiving normal saline were also included in the study. Twenty-four hr after the last dose, the animals were sacrificed and the plasma levels of endothelin-1 and nitric oxide in addition to cardiac nitric oxide were determined. The results show that doxorubicin caused a statistically significant increase of 85%, 76% and 97% in plasma endothelin-1 at a cumulative dose levels of 10, 15 and 20 mg/kg, respectively. However, the level of plasma nitric oxide remained unchanged. Furthermore, doxorubicin treatment resulted in a significant dose-dependent increase in serum lactate dehydrogenase and creatine phosphokinase. In contrast, the increase in nitric oxide production in cardiac tissue by doxorubicin was not dose-dependent with the maximum increase (81%) at a cumulative dose of 10 mg/kg. It is worth mentioning that plasma endothelin-1 and cardiac nitric oxide were significantly increased at 24 hr after the single dose of 20 mg/kg doxorubicin. The increase of plasma endothelin-1 and cardiac nitric oxide with the cardiomyopathy enzymatic indices, may point to the conclusion that both endothelin-1 and cardiac nitric oxide are increased during the development of doxorubicin-induced cardiomyopathy. JF - Pharmacology & toxicology AU - Sayed-Ahmed, M M AU - Khattab, M M AU - Gad, M Z AU - Osman, A M AD - Pharmacology Unit, National Cancer Institute, Cairo, Egypt. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 140 EP - 144 VL - 89 IS - 3 SN - 0901-9928, 0901-9928 KW - Endothelin-1 KW - 0 KW - Vasodilator Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Doxorubicin KW - 80168379AG KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Creatine Kinase KW - EC 2.7.3.2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Creatine Kinase -- blood KW - L-Lactate Dehydrogenase -- drug effects KW - Creatine Kinase -- drug effects KW - L-Lactate Dehydrogenase -- blood KW - Male KW - Endothelin-1 -- blood KW - Doxorubicin -- pharmacology KW - Nitric Oxide -- blood KW - Cardiomyopathy, Dilated -- chemically induced KW - Myocardium -- metabolism KW - Cardiomyopathy, Dilated -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72180925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+toxicology&rft.atitle=Increased+plasma+endothelin-1+and+cardiac+nitric+oxide+during+doxorubicin-induced+cardiomyopathy.&rft.au=Sayed-Ahmed%2C+M+M%3BKhattab%2C+M+M%3BGad%2C+M+Z%3BOsman%2C+A+M&rft.aulast=Sayed-Ahmed&rft.aufirst=M&rft.date=2001-09-01&rft.volume=89&rft.issue=3&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+toxicology&rft.issn=09019928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-14 N1 - Date created - 2001-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical pathways for managing patients receiving interleukin 2. AN - 71288699; 11905416 AB - As biologic therapies enter the mainstream for cancer and HIV treatments, clinicians need the knowledge and expertise to safely and competently care for their patients who are undergoing these therapies. This article provides an overview of the immune system, emphasizing the elements that are affected by the biologic agent interleukin 2 (lL-2), lL-2 has been approved for use in the treatment of metastatic renal cell carcinoma and metastatic melanoma. Clinical trials currently are being conducted to determine its use in treating other cancers. The severity of side effects of lL-2 varies with the dose, route, and schedule of administration. The most common effects with all methods of administration are flu-like symptoms. Because the side effects of lL-2 are relatively predictable, clinical pathways offer practical tools for anticipating and managing the toxicities associated with lL-2 administration. JF - Clinical journal of oncology nursing AU - Mavroukakis, S A AU - Muehlbauer, P M AU - White, R L AU - Schwartzentruber, D J AD - Sharon_Mavroukakis@nih.gov PY - 2001 SP - 207 EP - 217 VL - 5 IS - 5 SN - 1092-1095, 1092-1095 KW - Antineoplastic Agents KW - 0 KW - Interleukin-2 KW - Nursing KW - Immunotherapy KW - Humans KW - Melanoma -- drug therapy KW - Critical Pathways KW - Immune System -- physiology KW - Kidney Neoplasms -- drug therapy KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Carcinoma, Renal Cell -- secondary KW - Carcinoma, Renal Cell -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71288699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+journal+of+oncology+nursing&rft.atitle=Clinical+pathways+for+managing+patients+receiving+interleukin+2.&rft.au=Mavroukakis%2C+S+A%3BMuehlbauer%2C+P+M%3BWhite%2C+R+L%3BSchwartzentruber%2C+D+J&rft.aulast=Mavroukakis&rft.aufirst=S&rft.date=2001-09-01&rft.volume=5&rft.issue=5&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Clinical+journal+of+oncology+nursing&rft.issn=10921095&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-23 N1 - Date created - 2002-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and evaluation of 2-chloroethylnitrosoureas of substituted naphthalimides as mixed-function anticancer compounds. AN - 71265777; 11876442 AB - New mixed function anticancer compounds as 2-chloroethylnitrosoureas of substituted naphthalimides represented by bromonap-NU 4a and chloronap-NU 4b, have been synthesized from 4-bromo- and 4-chloro-l,8-naphthalic anhydride, respectively following a 3-step process. Their chemical alkylating activity compared with nor -HN2 indicated that they possess greater alkylating activity than the latter. Their antitumour efficacies were assessed in vivo in two murine ascites tumours, namely Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Two standard clinical drugs namely endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Both of them have displayed substantial and reproducible antitumoral activity in these tumours comparable with 5-FU. These were further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines. JF - Acta poloniae pharmaceutica AU - Samanta, S AU - Pain, A AU - Dutta, S AU - Sanyal, U AD - Department of Anticancer Drug Development & Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. PY - 2001 SP - 351 EP - 356 VL - 58 IS - 5 SN - 0001-6837, 0001-6837 KW - 6-bromo-2-(2-(3-(2-chloroethyl)-3-nitrosoureido)ethyl)-1H-benz-(de)isoquinoline-1,3-dione KW - 0 KW - 6-chloro-2-(2-(3-(2-chloroethyl)-3-nitrosoureido)ethyl)-1H-benz-(de)isoquinoline-1,3-dione KW - Antineoplastic Agents, Alkylating KW - Isoquinolines KW - Naphthalimides KW - Nitrosourea Compounds KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Animals KW - Tumor Cells, Cultured KW - Sarcoma 180 -- mortality KW - Humans KW - Carcinoma, Ehrlich Tumor -- mortality KW - Mice KW - Isoquinolines -- pharmacology KW - Nitrosourea Compounds -- pharmacology KW - Antineoplastic Agents, Alkylating -- chemical synthesis KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Nitrosourea Compounds -- chemical synthesis KW - Isoquinolines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71265777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+poloniae+pharmaceutica&rft.atitle=Synthesis+and+evaluation+of+2-chloroethylnitrosoureas+of+substituted+naphthalimides+as+mixed-function+anticancer+compounds.&rft.au=Samanta%2C+S%3BPain%2C+A%3BDutta%2C+S%3BSanyal%2C+U&rft.aulast=Samanta&rft.aufirst=S&rft.date=2001-09-01&rft.volume=58&rft.issue=5&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=Acta+poloniae+pharmaceutica&rft.issn=00016837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-23 N1 - Date created - 2002-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol use disorders and anxiety disorders: relation to the P300 event-related potential. AN - 71213115; 11584148 AB - The robust association of alcoholism with reduced P300 event-related potential amplitude has been largely established in severely affected alcoholics and their offspring. Few studies have examined the relationship of increased arousal, anxiety, and P300. In this study, we sought to determine whether P300 group differences could be discerned in well functioning individuals with less severe forms of alcohol use disorders and anxiety disorders. We were particularly interested in looking at the subgroup of alcohol use disorders accompanied by anxiety disorders. This subgroup has previously been found to have diminished alpha amplitude in the resting EEG. Male and female community volunteers (99 unrelated index participants and 78 relatives) and 21 unrelated volunteers from an anxiety disorder clinic were interviewed by using the Schedule for Affective Disorders and Schizophrenia, Lifetime version. Blind-rated lifetime psychiatric diagnoses were assigned according to DSM-III-R criteria. Auditory and visual P300 event-related potentials were elicited with an oddball paradigm and were recorded at the midparietal (Pz) site. As expected, auditory P300 amplitudes were significantly reduced in participants with alcohol use disorders and significantly increased in participants with lifetime anxiety disorders. However, more detailed analysis revealed that, in an apparent paradox, auditory P300 amplitudes were lowest in individuals with comorbid alcohol use and anxiety disorders and highest in individuals with anxiety disorders alone. Visual P300 amplitudes followed the same trends but were generally not significant. Even in a sample of largely community-ascertained individuals, auditory P300 amplitude is reduced in alcoholics, particularly those with anxiety disorders, and is highest in nonalcoholics with anxiety disorders. JF - Alcoholism, clinical and experimental research AU - Enoch, M A AU - White, K V AU - Harris, C R AU - Rohrbaugh, J W AU - Goldman, D AD - Laboratory of Neurogenetics, NIAAA, NIH, Bethesda, Maryland 20892-8110, USA. maenoch@dicbr.niaaa.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1293 EP - 1300 VL - 25 IS - 9 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Smoking -- physiopathology KW - Age Factors KW - Evoked Potentials, Visual KW - Sex Characteristics KW - Humans KW - Adult KW - Personality KW - Evoked Potentials, Auditory KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Anxiety -- physiopathology KW - Event-Related Potentials, P300 KW - Alcoholism -- physiopathology KW - Anxiety -- complications KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71213115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Alcohol+use+disorders+and+anxiety+disorders%3A+relation+to+the+P300+event-related+potential.&rft.au=Enoch%2C+M+A%3BWhite%2C+K+V%3BHarris%2C+C+R%3BRohrbaugh%2C+J+W%3BGoldman%2C+D&rft.aulast=Enoch&rft.aufirst=M&rft.date=2001-09-01&rft.volume=25&rft.issue=9&rft.spage=1293&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Screening for high- and moderate-risk drinking during pregnancy: a comparison of several TWEAK-based screeners. AN - 71213112; 11584155 AB - This study investigated the use of the TWEAK and nine alternative screeners for predicting high-risk and moderate-risk drinking during pregnancy. The analysis was based on self-reports from 404 lifetime drinkers who presented for an initial visit at nine prenatal clinics in Washington, DC. Data were collected anonymously by having women directly enter their responses onto an audio, computer-assisted interview that was programmed onto a laptop computer. Pregnancy risk drinking status was based on both average daily volume of intake and frequency of drinking 3+ drinks in a day. Each of the alternative screeners was constructed by adding one additional risk indicator to the TWEAK, and three different scoring options were explored. Using thresholds of 2 points for high-risk drinking and 1 point for moderate-risk drinking, the TWEAK demonstrated a sensitivity and specificity of 70.6% and 73.2% for high-risk drinking and a sensitivity and specificity of 65.6% and 63.7% for any (high- or moderate-) risk drinking during pregnancy. None of the alternative screeners resulted in significant improvement, but the addition of current smoking status showed enough promise to warrant further testing in larger samples. Despite some loss in sensitivity and specificity, the TWEAK, in its original or a modified form, can be extended to measures of high-risk drinking that incorporate infrequent heavy intake and can be used to test for moderate- as well as high-risk drinking. Because identification of moderate-risk drinkers substantially increases the pool of women targeted for intervention, cost implications must be considered in designing appropriate interventions. JF - Alcoholism, clinical and experimental research AU - Dawson, D A AU - Das, A AU - Faden, V B AU - Bhaskar, B AU - Krulewitch, C J AU - Wesley, B AD - NIAAA, NIH, Bethesda, Maryland 20892-7003, USA. ddawson@willco.niaaa.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1342 EP - 1349 VL - 25 IS - 9 SN - 0145-6008, 0145-6008 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Sensitivity and Specificity KW - Anxiety KW - Alcoholism -- diagnosis KW - Humans KW - Gestational Age KW - Risk Assessment -- methods KW - Alcoholism -- psychology KW - Pregnancy KW - Smoking KW - Drug Tolerance KW - Adult KW - Amnesia KW - Female KW - Ethanol -- adverse effects KW - Ethanol -- administration & dosage KW - Alcohol Drinking -- psychology KW - Mass Screening -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71213112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Screening+for+high-+and+moderate-risk+drinking+during+pregnancy%3A+a+comparison+of+several+TWEAK-based+screeners.&rft.au=Dawson%2C+D+A%3BDas%2C+A%3BFaden%2C+V+B%3BBhaskar%2C+B%3BKrulewitch%2C+C+J%3BWesley%2C+B&rft.aulast=Dawson&rft.aufirst=D&rft.date=2001-09-01&rft.volume=25&rft.issue=9&rft.spage=1342&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coronary vasospasm as a cause of effort-related myocardial ischemia during low-dose chronic continuous infusion of 5-fluorouracil. AN - 71206095; 11566462 JF - The American journal of medicine AU - Lestuzzi, C AU - Viel, E AU - Picano, E AU - Meneguzzo, N AD - Cardiology Department, Centro di Riferimento Oncologico, National Cancer Institute, 33081 Aviano, Italy. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 316 EP - 318 VL - 111 IS - 4 SN - 0002-9343, 0002-9343 KW - Antineoplastic Agents KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Exercise Test KW - Infusions, Intravenous KW - Humans KW - Electrocardiography KW - Adult KW - Antineoplastic Combined Chemotherapy Protocols KW - Aged KW - Middle Aged KW - Adenocarcinoma -- drug therapy KW - Female KW - Fluorouracil -- therapeutic use KW - Myocardial Ischemia -- etiology KW - Fluorouracil -- adverse effects KW - Coronary Vasospasm -- chemically induced KW - Coronary Vasospasm -- complications KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71206095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+medicine&rft.atitle=Coronary+vasospasm+as+a+cause+of+effort-related+myocardial+ischemia+during+low-dose+chronic+continuous+infusion+of+5-fluorouracil.&rft.au=Lestuzzi%2C+C%3BViel%2C+E%3BPicano%2C+E%3BMeneguzzo%2C+N&rft.aulast=Lestuzzi&rft.aufirst=C&rft.date=2001-09-01&rft.volume=111&rft.issue=4&rft.spage=316&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Med. 2001 Sep;111(4):326-7 [11566467] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Guidelines for Prevention of Pneumocystis carinii Pneumonitis in Children and Adolescents with Cancer]. TT - Empfehlungen zur Prävention der Pneumocystis-carinii-Pneumonie bei Kindern und Jugendlichen mit neoplastischen Erkrankungen. AN - 71201280; 11577363 AB - Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population. JF - Klinische Padiatrie AU - Groll, A H AU - Ritter, J AU - Müller, F M AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bldg. 10, Room 13N-240, Bethesda, MD 20892, USA. grolla@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - A38 EP - A49 VL - 213 Suppl 1 SN - 0300-8630, 0300-8630 KW - Anti-Bacterial Agents KW - 0 KW - Anti-Infective Agents KW - Antifungal Agents KW - Naphthoquinones KW - Pentamidine KW - 673LC5J4LQ KW - Trimethoprim, Sulfamethoxazole Drug Combination KW - 8064-90-2 KW - Dapsone KW - 8W5C518302 KW - Atovaquone KW - Y883P1Z2LT KW - Index Medicus KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Randomized Controlled Trials as Topic KW - Odds Ratio KW - Age Factors KW - Humans KW - Child KW - Child, Preschool KW - Infant KW - Prospective Studies KW - Risk Factors KW - Practice Guidelines as Topic KW - Hematopoietic Stem Cell Transplantation KW - Drug Therapy, Combination -- therapeutic use KW - Immunocompromised Host KW - Adolescent KW - Time Factors KW - Trimethoprim, Sulfamethoxazole Drug Combination -- administration & dosage KW - Dapsone -- adverse effects KW - Naphthoquinones -- therapeutic use KW - Antifungal Agents -- adverse effects KW - Dapsone -- administration & dosage KW - Trimethoprim, Sulfamethoxazole Drug Combination -- therapeutic use KW - Naphthoquinones -- adverse effects KW - Trimethoprim, Sulfamethoxazole Drug Combination -- adverse effects KW - Antifungal Agents -- therapeutic use KW - Pneumonia, Pneumocystis -- prevention & control KW - Anti-Infective Agents -- therapeutic use KW - Pentamidine -- administration & dosage KW - Neoplasms -- complications KW - Anti-Infective Agents -- adverse effects KW - Naphthoquinones -- administration & dosage KW - Anti-Infective Agents -- administration & dosage KW - Pentamidine -- adverse effects KW - Antifungal Agents -- administration & dosage KW - Pentamidine -- therapeutic use KW - Dapsone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71201280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Klinische+Padiatrie&rft.atitle=%5BGuidelines+for+Prevention+of+Pneumocystis+carinii+Pneumonitis+in+Children+and+Adolescents+with+Cancer%5D.&rft.au=Groll%2C+A+H%3BRitter%2C+J%3BM%C3%BCller%2C+F+M&rft.aulast=Groll&rft.aufirst=A&rft.date=2001-09-01&rft.volume=213+Suppl+1&rft.issue=&rft.spage=A38&rft.isbn=&rft.btitle=&rft.title=Klinische+Padiatrie&rft.issn=03008630&rft_id=info:doi/ LA - ger DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new isoquinoline alkaloid from the marine sponge Haliclona species. AN - 71199556; 11575970 AB - Two isoquinoline alkaloids, including the new compound 1, were isolated from the cytotoxic fractions of an aqueous extract of the marine sponge Haliclona sp. The structures of these compounds were established as 1-hydroxymethyl-7-methoxyisoquinolin-6-ol (1) and mimosamycin (2) by conventional spectroscopic methods and by comparison with related compounds. Mimosamycin (2) was the principal cytotoxin with an IC(50) of approximately 10 microg/mL against melanoma and ovarian human tumor cell lines. JF - Journal of natural products AU - Rashid, M A AU - Gustafson, K R AU - Boyd, M R AD - Molecular Targets Drug Discovery Program, Center for Cancer Research, National Cancer Institute-Frederick, Building 1052, Room 121, Frederick, Maryland 21702-1201, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1249 EP - 1250 VL - 64 IS - 9 SN - 0163-3864, 0163-3864 KW - 1-hydroxymethyl-7-methoxyisoquinolin-6-ol KW - 0 KW - Alkaloids KW - Antineoplastic Agents KW - Isoquinolines KW - mimosamycin KW - 59493-94-6 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Drug Screening Assays, Antitumor KW - Philippines KW - Ovarian Neoplasms KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Melanoma KW - Spectrophotometry, Infrared KW - Inhibitory Concentration 50 KW - Female KW - Isoquinolines -- pharmacology KW - Isoquinolines -- chemistry KW - Alkaloids -- chemistry KW - Antineoplastic Agents -- isolation & purification KW - Porifera -- chemistry KW - Alkaloids -- pharmacology KW - Alkaloids -- isolation & purification KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology KW - Isoquinolines -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71199556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=A+new+isoquinoline+alkaloid+from+the+marine+sponge+Haliclona+species.&rft.au=Rashid%2C+M+A%3BGustafson%2C+K+R%3BBoyd%2C+M+R&rft.aulast=Rashid&rft.aufirst=M&rft.date=2001-09-01&rft.volume=64&rft.issue=9&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thrombogenic influence of biomaterials in patients with the Omni series heart valve: pyrolytic carbon versus titanium. AN - 71198463; 11575807 AB - An opportunity to assess the thromboembolic rates caused by the construction materials on valve replacements is possible with the Omni series of mechanical heart valves. The Omnicarbon and Omniscience valves are identical in form but differ in that the Omnicarbon valve is constructed entirely of pyrolytic carbon, whereas the Omniscience valve uses titanium for its housing, the rest of its structure being pyrolytic carbon. The literature was reviewed and a comparison in similar groups of patients was made between these two model valves for their thromboembolic rates in the mitral and aortic positions. A total of 569 aortic Omnicarbon valves (4,146 patient years [pt yrs.1) had a thromboembolic events (T/E rate) of 0.5% compared with 1.7% for 468 aortic Omniscience (1,552 pt yrs); p < 0.0001. A total of 298 mitral Omnicarbon valves (3,333 pt yrs) had a T/E rate of 1.6% compared with 2.6% for 716 mitral Omniscience valves (2,134 pt yrs), p < 0.001. There was no difference in the anticoagulation management between the two model valves although the Omniscience valve required higher prothrombin or International Normalized Rate maintenance levels, which resulted in higher bleeding rates among patients with Omniscience valves. JF - ASAIO journal (American Society for Artificial Internal Organs : 1992) AU - Phillips, S J AD - National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. PY - 2001 SP - 429 EP - 431 VL - 47 IS - 5 SN - 1058-2916, 1058-2916 KW - Anticoagulants KW - 0 KW - Biocompatible Materials KW - pyrolytic carbon KW - Warfarin KW - 5Q7ZVV76EI KW - Carbon KW - 7440-44-0 KW - Titanium KW - D1JT611TNE KW - Index Medicus KW - Anticoagulants -- therapeutic use KW - Humans KW - Anticoagulants -- adverse effects KW - Warfarin -- adverse effects KW - Prosthesis Design KW - Warfarin -- therapeutic use KW - Mitral Valve KW - Aortic Valve KW - Hemorrhage -- etiology KW - Titanium -- adverse effects KW - Biocompatible Materials -- adverse effects KW - Carbon -- adverse effects KW - Thrombosis -- etiology KW - Heart Valve Prosthesis -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71198463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ASAIO+journal+%28American+Society+for+Artificial+Internal+Organs+%3A+1992%29&rft.atitle=Thrombogenic+influence+of+biomaterials+in+patients+with+the+Omni+series+heart+valve%3A+pyrolytic+carbon+versus+titanium.&rft.au=Phillips%2C+S+J&rft.aulast=Phillips&rft.aufirst=S&rft.date=2001-09-01&rft.volume=47&rft.issue=5&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=ASAIO+journal+%28American+Society+for+Artificial+Internal+Organs+%3A+1992%29&rft.issn=10582916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-26 N1 - Date created - 2001-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transferring genes to salivary glands. AN - 71190767; 11569607 AB - This review provides a brief description of gene transfer studies using salivary glands as the target tissue. The aggregate results demonstrate the potential clinical value of this methodological approach for managing several conditions lacking fully satisfactory conventional treatments. Routine clinical applications are still seven to ten years away, primarily because of the need for improved gene transfer vectors. Overall, this body of work provides the dental educator with a substantive example of how biotechnological progress will significantly affect the treatment of oral problems in the near future. JF - Journal of dental education AU - Simmons, R K AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 907 EP - 910 VL - 65 IS - 9 SN - 0022-0337, 0022-0337 KW - Salivary Proteins and Peptides KW - 0 KW - Dentistry KW - Index Medicus KW - Xerostomia -- etiology KW - Humans KW - Genetic Vectors KW - Sjogren's Syndrome -- therapy KW - Salivary Proteins and Peptides -- genetics KW - Xerostomia -- therapy KW - Genetic Therapy KW - Biotechnology KW - Radiotherapy -- adverse effects KW - Adenoviridae -- genetics KW - Gene Transfer Techniques KW - Salivary Glands -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71190767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+dental+education&rft.atitle=Transferring+genes+to+salivary+glands.&rft.au=Simmons%2C+R+K%3BBaum%2C+B+J&rft.aulast=Simmons&rft.aufirst=R&rft.date=2001-09-01&rft.volume=65&rft.issue=9&rft.spage=907&rft.isbn=&rft.btitle=&rft.title=Journal+of+dental+education&rft.issn=00220337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta. AN - 71181236; 11560886 AB - Several amino acids in the active site of family A DNA polymerases contribute to accurate DNA synthesis. For two of these residues, family B DNA polymerases have conserved tyrosine residues in regions II and III that are suggested to have similar functions. Here we replaced each tyrosine with alanine in the catalytic subunits of yeast DNA polymerases alpha, delta, epsilon, and zeta and examined the consequences in vivo. Strains with the tyrosine substitution in the conserved SL/MYPS/N motif in region II in Pol delta or Pol epsilon are inviable. Strains with same substitution in Rev3, the catalytic subunit of Pol zeta, are nearly UV immutable, suggesting severe loss of function. A strain with this substitution in Pol alpha (pol1-Y869A) is viable, but it exhibits slow growth, sensitivity to hydroxyurea, and a spontaneous mutator phenotype for frameshifts and base substitutions. The pol1-Y869A/pol1-Y869A diploid exhibits aberrant growth. Thus, this tyrosine is critical for the function of all four eukaryotic family B DNA polymerases. Strains with a tyrosine substitution in the conserved NS/VxYG motif in region III in Pol alpha, -delta, or -epsilon are viable and a strain with the homologous substitution in Rev3 is UV mutable. The Pol alpha mutant has no obvious phenotype. The Pol epsilon (pol2-Y831A) mutant is slightly sensitive to hydroxyurea and is a semidominant mutator for spontaneous base substitutions and frameshifts. The Pol delta mutant (pol3-Y708A) grows slowly, is sensitive to hydroxyurea and methyl methanesulfonate, and is a strong base substitution and frameshift mutator. The pol3-Y708A/pol3-Y708A diploid grows slowly and aberrantly. Mutation rates in the Pol alpha, -delta, and -epsilon mutant strains are increased in a locus-specific manner by inactivation of PMS1-dependent DNA mismatch repair, suggesting that the mutator effects are due to reduced fidelity of chromosomal DNA replication. This could result directly from relaxed base selectivity of the mutant polymerases due to the amino acid changes in the polymerase active site. In addition, the alanine substitutions may impair catalytic function to allow a different polymerase to compete at the replication fork. This is supported by the observation that the pol3-Y708A mutation is recessive and its mutator effect is partially suppressed by disruption of the REV3 gene. JF - Genetics AU - Pavlov, Y I AU - Shcherbakova, P V AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. pavlov@niehs.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 47 EP - 64 VL - 159 IS - 1 SN - 0016-6731, 0016-6731 KW - DNA Primers KW - 0 KW - Tyrosine KW - 42HK56048U KW - DNA KW - 9007-49-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - DNA Polymerase I KW - EC 2.7.7.- KW - DNA Polymerase II KW - DNA Polymerase III KW - DNA polymerase zeta KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Alanine KW - OF5P57N2ZX KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Ultraviolet Rays KW - Methyl Methanesulfonate -- pharmacology KW - Frameshift Mutation KW - Phenotype KW - Alleles KW - Amino Acid Motifs KW - Heterozygote KW - Molecular Sequence Data KW - Point Mutation KW - Sequence Homology, Amino Acid KW - DNA -- radiation effects KW - DNA Primers -- metabolism KW - Diploidy KW - Plasmids -- metabolism KW - DNA Repair KW - Homozygote KW - Amino Acid Sequence KW - Alanine -- chemistry KW - Hydroxyurea -- pharmacology KW - Saccharomyces cerevisiae -- enzymology KW - Dose-Response Relationship, Radiation KW - Protein Binding KW - Binding Sites KW - Tyrosine -- chemistry KW - Conserved Sequence KW - Base Pair Mismatch KW - Models, Genetic KW - Protein Structure, Tertiary KW - Catalysis KW - DNA Polymerase I -- genetics KW - DNA Polymerase III -- genetics KW - DNA Polymerase II -- genetics KW - Mutation KW - DNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71181236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=In+vivo+consequences+of+putative+active+site+mutations+in+yeast+DNA+polymerases+alpha%2C+epsilon%2C+delta%2C+and+zeta.&rft.au=Pavlov%2C+Y+I%3BShcherbakova%2C+P+V%3BKunkel%2C+T+A&rft.aulast=Pavlov&rft.aufirst=Y&rft.date=2001-09-01&rft.volume=159&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-04 N1 - Date created - 2001-09-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Biol. 2000 Oct 5;10(19):1213-6 [11050391] Yeast. 1999 Oct;15(14):1541-53 [10514571] Curr Biol. 2000 Oct 5;10(19):1221-4 [11050393] Mol Cell. 2000 Dec;6(6):1491-9 [11163221] Nat Rev Mol Cell Biol. 2000 Nov;1(2):101-9 [11253362] Proc Natl Acad Sci U S A. 1981 Sep;78(9):5778-82 [7029545] Methods Enzymol. 1983;100:293-308 [6312261] Proc Natl Acad Sci U S A. 1987 May;84(9):2838-42 [3554248] Cell. 1989 Feb 24;56(4):619-30 [2645056] J Bacteriol. 1989 Oct;171(10):5659-67 [2676986] Protein Eng. 1990 May;3(6):461-7 [2196557] Biochemistry. 1990 Jun 5;29(22):5226-31 [2166556] Biochemistry. 1991 Jan 22;30(3):804-13 [1899034] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9473-7 [1658784] Structure. 1999 Oct 15;7(10):1189-99 [10545321] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5681-3 [10811923] Genetics. 2000 Aug;155(4):1623-32 [10924461] Nature. 2000 Aug 31;406(6799):1015-9 [10984059] J Biol Chem. 1992 Apr 25;267(12):8417-28 [1569092] Mol Cell Biol. 1993 Jan;13(1):496-505 [8417347] Chromosoma. 1992;102(1 Suppl):S147-9 [1291235] EMBO J. 1993 Apr;12(4):1467-73 [8385605] J Biol Chem. 1993 Nov 15;268(32):24163-74 [8226963] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] J Biol Chem. 1994 Feb 25;269(8):5635-43 [8119900] Biochemistry. 1994 Dec 13;33(49):14908-17 [7993917] Yeast. 1994 Dec;10(13):1793-808 [7747518] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Gene. 1995 Aug 30;162(1):157-8 [7557406] Genes Dev. 1996 Feb 15;10(4):407-20 [8600025] Mutat Res. 1996 Jul 10;369(1-2):33-44 [8700180] Mol Cell Biol. 1999 Nov;19(11):7801-15 [10523669] Genetics. 1996 Jan;142(1):65-78 [8770585] Genetics. 1996 Mar;142(3):717-26 [8849882] Cancer Surv. 1996;28:21-31 [8977026] Mol Cell Biol. 1997 Feb;17(2):1027-36 [9001255] J Biol Chem. 1997 Mar 14;272(11):7345-51 [9054433] Cell. 1997 Jun 27;89(7):1087-99 [9215631] Genetics. 1997 Nov;147(3):1017-24 [9383049] Genetics. 1997 Dec;147(4):1557-68 [9409821] Mol Gen Genet. 1998 Feb;257(3):362-7 [9520271] Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3402-7 [9520378] Mol Cell Biol. 1998 May;18(5):2779-88 [9566897] Mol Cell. 1998 Jul;2(1):9-22 [9702187] Annu Rev Biochem. 1998;67:721-51 [9759502] J Biol Chem. 1999 Jan 29;274(5):3067-75 [9915846] Mol Cell Biol. 1999 Apr;19(4):3177-83 [10082584] Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3600-5 [10097083] Genetics. 1999 May;152(1):47-59 [10224242] Mol Cell. 1999 May;3(5):679-85 [10360184] EMBO J. 1999 Jun 15;18(12):3491-501 [10369688] J Mol Biol. 1999 Jun 18;289(4):835-50 [10369765] Biochemistry. 1999 Jun 22;38(25):8094-101 [10387055] J Biol Chem. 1999 Aug 13;274(33):23599-609 [10438542] Cell. 1999 Aug 20;98(4):413-6 [10481906] Curr Biol. 2000 Oct 5;10(19):1217-20 [11050392] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents. AN - 71171814; 11557916 AB - Elevations of inflammatory cytokines have been reported in animal models of acetaminophen (INN, paracetamol) toxicity. In addition, interleukin 8, a chemokine, has been found to be elevated in toxin-associated hepatic disease (ie, acute alcoholic hepatitis). The purpose of this study was to measure serum cytokine levels in children and adolescents with acetaminophen overdose and to evaluate relationships between cytokine elevation and hepatotoxicity. Serum levels of tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, and interleukin 10 were measured by ELISA in children and adolescents (n = 35) with acetaminophen overdose. Peak cytokine levels were examined relative to biochemical evidence of hepatocellular injury, nomogram risk assessment, and prothrombin time. Five patients had aspartate aminotransferase or alanine aminotransferase levels >1000 IU/L, and 4 patients had aspartate aminotransferase or alanine aminotransferase levels > or =100 IU/L and 15 hours, as compared with other patients (Mann-Whitney U test, P 20 pg/mL were associated with peak prothrombin time values (Mann-Whitney exact test, P <.015). Interleukin 8 elevation in patients with acetaminophen hepatotoxicity corresponds with other common clinical measures that are predictive of hepatocellular injury. Further study is warranted to evaluate possible mechanistic relationships between inflammatory cytokines and acetaminophen hepatotoxicity in children and adults. JF - Clinical pharmacology and therapeutics AU - James, L P AU - Farrar, H C AU - Darville, T L AU - Sullivan, J E AU - Givens, T G AU - Kearns, G L AU - Wasserman, G S AU - Simpson, P M AU - Hinson, J A AU - Pediatric Pharmacology Research Unit Network, National Institute of Child Health and Human Development AD - Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock 72202, USA. Jameslaurap@uams.edu ; Pediatric Pharmacology Research Unit Network, National Institute of Child Health and Human Development Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 280 EP - 286 VL - 70 IS - 3 SN - 0009-9236, 0009-9236 KW - Analgesics, Non-Narcotic KW - 0 KW - Interleukin-8 KW - Acetaminophen KW - 362O9ITL9D KW - Acetylcysteine KW - WYQ7N0BPYC KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Chemical and Drug Induced Liver Injury -- blood KW - Humans KW - Acetylcysteine -- therapeutic use KW - Child KW - Prothrombin Time KW - Liver Function Tests KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Analgesics, Non-Narcotic -- poisoning KW - Acetaminophen -- poisoning KW - Interleukin-8 -- blood KW - Drug Overdose -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71171814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Elevation+of+serum+interleukin+8+levels+in+acetaminophen+overdose+in+children+and+adolescents.&rft.au=James%2C+L+P%3BFarrar%2C+H+C%3BDarville%2C+T+L%3BSullivan%2C+J+E%3BGivens%2C+T+G%3BKearns%2C+G+L%3BWasserman%2C+G+S%3BSimpson%2C+P+M%3BHinson%2C+J+A%3BPediatric+Pharmacology+Research+Unit+Network%2C+National+Institute+of+Child+Health+and+Human+Development&rft.aulast=James&rft.aufirst=L&rft.date=2001-09-01&rft.volume=70&rft.issue=3&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=00099236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recruitment of HU by piggyback: a special role of GalR in repressosome assembly. AN - 71159943; 11544184 AB - In Gal repressosome assembly, a DNA loop is formed by the interaction of two GalR, bound to two distal operators, and the binding of the histone-like protein, HU, to an architecturally critical position on DNA to facilitate the GalR-GalR interaction. We show that GalR piggybacks HU to the critical position on the DNA through a specific GalR-HU interaction. This is the first example of HU making a specific contact with another protein. The GalR-HU contact that results in cooperative binding of the two proteins to DNA may be transient and absent in the final repressosome structure. A sequence-independent DNA-binding protein being recruited to an architectural site on DNA through a specific association with a regulatory protein may be a common mode for assembly of complex nucleoprotein structures. JF - Genes & development AU - Kar, S AU - Adhya, S AD - Department of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 2273 EP - 2281 VL - 15 IS - 17 SN - 0890-9369, 0890-9369 KW - Amino Acids KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Galactose repressor proteins KW - Repressor Proteins KW - hns protein, E coli KW - DNA KW - 9007-49-2 KW - Glucuronidase KW - EC 3.2.1.31 KW - Index Medicus KW - Plasmids -- metabolism KW - Escherichia coli -- metabolism KW - Cell Nucleus -- metabolism KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - DNA -- metabolism KW - Dimerization KW - Glucuronidase -- metabolism KW - Transcription, Genetic KW - Precipitin Tests KW - Protein Binding KW - Models, Biological KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Blotting, Western KW - Amino Acids -- chemistry KW - Models, Genetic KW - Chromosomes -- metabolism KW - Mutation KW - Protein Conformation KW - DNA-Binding Proteins -- chemistry KW - Repressor Proteins -- physiology KW - Repressor Proteins -- metabolism KW - DNA-Binding Proteins -- physiology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71159943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=Recruitment+of+HU+by+piggyback%3A+a+special+role+of+GalR+in+repressosome+assembly.&rft.au=Kar%2C+S%3BAdhya%2C+S&rft.aulast=Kar&rft.aufirst=S&rft.date=2001-09-01&rft.volume=15&rft.issue=17&rft.spage=2273&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochimie. 1994;76(10-11):901-8 [7748933] EMBO J. 1995 Mar 15;14(6):1198-208 [7720710] J Mol Biol. 1995 Dec 8;254(4):692-703 [7500343] Electrophoresis. 1995 Jun;16(6):881-7 [7498130] EMBO J. 1996 Sep 16;15(18):4981-91 [8890171] Cell. 1997 Mar 21;88(6):733-6 [9118214] Genes Cells. 1996 Feb;1(2):179-88 [9140062] EMBO J. 1997 Jun 16;16(12):3666-74 [9218807] Genes Dev. 1998 Feb 15;12(4):462-72 [9472015] J Bacteriol. 1998 Apr;180(8):2063-71 [9555887] Mol Cell Biol. 1998 Aug;18(8):4471-87 [9671457] J Bacteriol. 1998 Aug;180(15):3750-6 [9683467] Mol Microbiol. 1999 Jan;31(2):451-61 [10027963] Genes Dev. 1999 May 15;13(10):1251-62 [10346814] Trends Biochem Sci. 2001 Mar;26(3):167-74 [11246022] Nat Struct Biol. 2001 May;8(5):432-6 [11323719] FEBS Lett. 1979 Oct 15;106(2):297-300 [227733] Nature. 1984 Aug 2-8;310(5976):376-81 [6540370] Microbiol Rev. 1987 Sep;51(3):301-19 [3118156] Gene. 1989;76(2):353-8 [2666261] J Biol Chem. 1990 Jan 25;265(3):1623-7 [2153137] Mol Gen Genet. 1990 Jan;220(2):197-203 [2183003] Biochemistry. 1990 Apr 3;29(13):3374-83 [2185837] EMBO J. 1990 Jul;9(7):2341-8 [1694129] J Biol Chem. 1991 Jan 15;266(2):1281-8 [1985947] J Mol Biol. 1991 Feb 20;217(4):721-9 [2005621] Gene. 1992 Oct 12;120(1):11-6 [1327969] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):472-6 [8380640] EMBO J. 1993 Jun;12(6):2503-12 [8508775] Genes Dev. 1993 Aug;7(8):1521-34 [8339930] J Biol Chem. 1994 Jun 3;269(22):15571-6 [8195202] Trends Biochem Sci. 1994 May;19(5):185-7 [8048157] J Bacteriol. 1994 Sep;176(17):5378-84 [8071215] Mol Microbiol. 1994 Oct;14(1):1-5 [7830547] Biochimie. 1994;76(10-11):992-1004 [7748943] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Limited heterogeneity of T cell receptor BV usage in aplastic anemia. AN - 71158671; 11544283 AB - Immune mediation of aplastic anemia (AA) has been inferred from clinical responsiveness to immunosuppressive therapies and a large body of circumstantial laboratory evidence. However, neither the immune response nor the nature of the antigens recognized has been well characterized. We established a large number of CD4 and CD8 T cell clones from a patient with AA and analyzed their T cell receptor (TCR) usage. Most CD4 clones displayed BV5, whereas most CD8 clones displayed BV13. We found sequence identity for complementarity determining region 3 (CDR3) among a majority of CD4 clones; the same sequence was present in marrow lymphocytes from four other patients with AA but was not detected in controls. The dominant CD4 clone showed a Th1 secretion pattern, lysed autologous CD34 cells, and inhibited their hematopoietic colony formation. In three of four patients, successful immunosuppressive treatment led to marked decrease in clones bearing the dominant CDR3 BV5 sequence. These results suggest surprisingly limited heterogeneity of the T cell repertoire in an individual patient and similarity at the molecular level of the likely pathological lymphocyte response among multiple patients with AA, consistent with recognition of limited numbers of antigens shared by individuals with the same HLA type in this disease. JF - The Journal of clinical investigation AU - Zeng, W AU - Maciejewski, J P AU - Chen, G AU - Young, N S AD - Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 765 EP - 773 VL - 108 IS - 5 SN - 0021-9738, 0021-9738 KW - Antigens, CD34 KW - 0 KW - Complementarity Determining Regions KW - Cytokines KW - Immunoglobulin Variable Region KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Hematopoietic Stem Cells -- chemistry KW - Cytokines -- biosynthesis KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Amino Acid Sequence KW - CD8-Positive T-Lymphocytes -- immunology KW - Complementarity Determining Regions -- genetics KW - Adult KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Middle Aged KW - Antigens, CD34 -- analysis KW - Colony-Forming Units Assay KW - Immunophenotyping KW - Immunoglobulin Variable Region -- genetics KW - Anemia, Aplastic -- genetics KW - Anemia, Aplastic -- immunology KW - CD4-Positive T-Lymphocytes -- immunology KW - Genes, T-Cell Receptor beta KW - Anemia, Aplastic -- diagnosis KW - CD4-Positive T-Lymphocytes -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71158671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Limited+heterogeneity+of+T+cell+receptor+BV+usage+in+aplastic+anemia.&rft.au=Zeng%2C+W%3BMaciejewski%2C+J+P%3BChen%2C+G%3BYoung%2C+N+S&rft.aulast=Zeng&rft.aufirst=W&rft.date=2001-09-01&rft.volume=108&rft.issue=5&rft.spage=765&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-09-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Biophys Res Commun. 1999 Sep 16;263(1):172-80 [10486273] J Immunol. 1999 Sep 15;163(6):3530-8 [10477628] Eur J Immunol. 1999 Oct;29(10):3360-8 [10540348] J Neuroimmunol. 2000 Feb 1;103(1):1-7 [10674983] Bone Marrow Transplant. 2000 Mar;25(6):623-32 [10734296] J Immunol. 2000 Jul 1;165(1):583-90 [10861099] Hum Immunol. 2000 Jul;61(7):675-83 [10880738] Cytometry. 2000 Aug 1;40(4):336-45 [10918284] Blood. 2000 Oct 1;96(7):2613-20 [11001919] Diabetologia. 2000 Dec;43(12):1484-97 [11151757] Philos Trans R Soc Lond B Biol Sci. 2001 Apr 29;356(1408):545-67 [11313011] Br J Haematol. 2001 Jul;114(1):57-62 [11472345] Blood. 2001 Dec 15;98(13):3513-9 [11739151] Br Med J. 1970 Apr 18;2(5702):131-6 [4909449] Blood. 1979 Mar;53(3):504-14 [32941] N Engl J Med. 1985 Jan 31;312(5):257-65 [2981406] Crit Rev Immunol. 1992;11(5):249-64 [1386519] Proc Natl Acad Sci U S A. 1993 May 1;90(9):4319-23 [8483950] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11049-53 [7504291] J Exp Med. 1994 Feb 1;179(2):609-18 [8294871] J Immunol. 1994 May 15;152(10):5109-19 [8176227] Blood. 1994 Oct 15;84(8):2815-20 [7919391] J Exp Med. 1994 Dec 1;180(6):2335-40 [7964506] J Exp Med. 1995 Jan 1;181(1):79-91 [7807026] Curr Opin Immunol. 1994 Dec;6(6):907-12 [7536011] Exp Hematol. 1995 May;23(5):433-8 [7720814] Immunol Today. 1995 Apr;16(4):176-81 [7734044] Res Immunol. 1995 Feb;146(2):65-80 [7481075] Blood. 1996 May 15;87(10):4149-57 [8639773] Clin Immunol Immunopathol. 1996 Aug;80(2):204-10 [8764566] Immunol Today. 1996 Jun;17(6):278-82 [8962631] Immunol Today. 1996 Mar;17(3):138-46 [8820272] Eur J Haematol Suppl. 1996;60:23-30 [8987237] N Engl J Med. 1997 May 8;336(19):1365-72 [9134878] Blood. 1997 May 15;89(10):3691-9 [9160674] Blood Cells Mol Dis. 1997;23(1):110-22 [9215756] Exp Hematol. 1997 Sep;25(10):1034-41 [9293900] Br J Haematol. 1997 Dec;99(3):517-9 [9401058] J Immunol. 1998 Jan 1;160(1):509-13 [9552010] J Immunol Methods. 1998 Jun 1;215(1-2):113-21 [9744753] J Immunol. 1999 Apr 1;162(7):3830-9 [10201900] Blood. 1999 May 1;93(9):3008-16 [10216097] J Exp Med. 1999 Jun 7;189(11):1823-38 [10359586] Hum Immunol. 1999 Aug;60(8):665-76 [10439312] Hum Immunol. 1999 Sep;60(9):798-805 [10527386] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing's syndrome. AN - 71157785; 11549633 AB - Chronic severe hypercortisolism is associated with life-threatening infections, diabetes and a high surgical mortality rate. Oral medical therapy can inhibit steroidogenesis and reduce the risk of these complications. However, apart from a few reports using an ethyl alcohol formulation of the iv anesthetic etomidate, there is no well-tested parenteral steroidogenesis inhibitor. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-yr-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5.5 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 d and perhaps as long as 6 wk after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. Parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications. JF - The Journal of clinical endocrinology and metabolism AU - Krakoff, J AU - Koch, C A AU - Calis, K A AU - Alexander, R H AU - Nieman, L K AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014, USA. jkrakoff@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 4104 EP - 4108 VL - 86 IS - 9 SN - 0021-972X, 0021-972X KW - Adrenal Cortex Hormones KW - 0 KW - Anesthetics, Intravenous KW - Drug Carriers KW - Propylene Glycols KW - Hydrocortisone KW - WI4X0X7BPJ KW - Etomidate KW - Z22628B598 KW - Abridged Index Medicus KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Adult KW - Adrenal Cortex Hormones -- blood KW - Acute Kidney Injury -- etiology KW - Adrenal Glands -- drug effects KW - Male KW - Hydrocortisone -- blood KW - Cushing Syndrome -- complications KW - Anesthetics, Intravenous -- therapeutic use KW - Cushing Syndrome -- surgery KW - Cushing Syndrome -- drug therapy KW - Anesthetics, Intravenous -- administration & dosage KW - Etomidate -- therapeutic use KW - Etomidate -- administration & dosage KW - Anesthetics, Intravenous -- adverse effects KW - Etomidate -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71157785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Use+of+a+parenteral+propylene+glycol-containing+etomidate+preparation+for+the+long-term+management+of+ectopic+Cushing%27s+syndrome.&rft.au=Krakoff%2C+J%3BKoch%2C+C+A%3BCalis%2C+K+A%3BAlexander%2C+R+H%3BNieman%2C+L+K&rft.aulast=Krakoff&rft.aufirst=J&rft.date=2001-09-01&rft.volume=86&rft.issue=9&rft.spage=4104&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine affects the dynamics of cytoskeletal proteins via sigma(1) receptors. AN - 71154672; 11543872 AB - Cytoskeletal proteins are important in protein trafficking, membrane protein clustering, dendrite growth and the morphological maintenance of neurons. Sigma(1) receptors are unique endoplasmic reticular (ER) proteins that bind (+)benzomorphans, neurosteroids and psychotropic drugs such as cocaine. Cocaine, via sigma(1) receptors, can cause the dissociation of a cytoskeletal adaptor protein ankyrin from inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] receptors on the ER as a sigma(1)-receptor-ankyrin complex, which then translocates to the plasma membrane and nucleus. The dissociation of sigma(1)-receptor-ankyrin from Ins(1,4,5)P(3) receptors also increases the intracellular Ca(2+) concentration [[Ca(2+)](i)], which affects the activity of cytoskeletal proteins. Furthermore, cocaine might increase [Ca(2+)](i) via phospholipase C (PLC)-linked dopamine D1 receptors. We hypothesize that cocaine might cause life-long changes in neurons via cytoskeletal proteins by interacting with both D1 receptors and sigma(1) receptors. JF - Trends in pharmacological sciences AU - Su, T P AU - Hayashi, T AD - Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. TSU@intra.nida.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 456 EP - 458 VL - 22 IS - 9 SN - 0165-6147, 0165-6147 KW - Cytoskeletal Proteins KW - 0 KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine D1 KW - Receptors, sigma KW - sigma-1 receptor KW - Cocaine KW - I5Y540LHVR KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Humans KW - Cytoskeletal Proteins -- drug effects KW - Receptors, sigma -- drug effects KW - Dopamine Uptake Inhibitors -- adverse effects KW - Calcium -- physiology KW - Receptors, Dopamine D1 -- drug effects KW - Cytoskeletal Proteins -- metabolism KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71154672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+pharmacological+sciences&rft.atitle=Cocaine+affects+the+dynamics+of+cytoskeletal+proteins+via+sigma%281%29+receptors.&rft.au=Su%2C+T+P%3BHayashi%2C+T&rft.aulast=Su&rft.aufirst=T&rft.date=2001-09-01&rft.volume=22&rft.issue=9&rft.spage=456&rft.isbn=&rft.btitle=&rft.title=Trends+in+pharmacological+sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Research sheds light on treatment interruption. AN - 71153618; 11547494 AB - Although there still is no clear answer about using structured treatment interruption as a therapeutic method with HIV patients, the strategy is gaining more respect as researchers from around the world continue to study it. Intermittent therapy, in which patients stop their antiretroviral therapy and then resume therapy in a cyclic way, may prove feasible, says one expert who spoke about interrupted treatment at the First International AIDS Society Conference on HIV Pathogenesis and Treatment in Buenos Aires, Argentina. JF - AIDS alert AU - Fauci, A Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 114 EP - 116 VL - 16 IS - 9 KW - Anti-HIV Agents KW - 0 KW - Reverse Transcriptase Inhibitors KW - AIDS/HIV KW - Viral Load KW - Reverse Transcriptase Inhibitors -- adverse effects KW - Drug Therapy, Combination KW - Drug Administration Schedule KW - Reverse Transcriptase Inhibitors -- administration & dosage KW - Humans KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - CD4 Lymphocyte Count KW - HIV Infections -- virology KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects KW - Anti-HIV Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71153618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=AIDS+alert&rft.atitle=Research+sheds+light+on+treatment+interruption.&rft.au=Fauci%2C+A&rft.aulast=Fauci&rft.aufirst=A&rft.date=2001-09-01&rft.volume=16&rft.issue=9&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=AIDS+alert&rft.issn=08870292&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. AN - 71144310; 11535692 AB - Many developing networks exhibit a transient period of spontaneous activity that is believed to be important developmentally. Here we investigate the initiation of spontaneous episodes of rhythmic activity in the embryonic chick spinal cord. These episodes recur regularly and are separated by quiescent intervals of many minutes. We examined the role of motoneurons and their intraspinal synaptic targets (R-interneurons) in the initiation of these episodes. During the latter part of the inter-episode interval, we recorded spontaneous, transient ventral root depolarizations that were accompanied by small, spatially diffuse fluorescent signals from interneurons retrogradely labeled with a calcium-sensitive dye. A transient often could be resolved at episode onset and was accompanied by an intense pre-episode (approximately 500 ms) motoneuronal discharge (particularly in adductor and sartorius) but not by interneuronal discharge monitored from the ventrolateral funiculus (VLF). An important role for this pre-episode motoneuron discharge was suggested by the finding that electrical stimulation of motor axons, sufficient to activate R-interneurons, could trigger episodes prematurely. This effect was mediated through activation of R-interneurons because it was prevented by pharmacological blockade of either the cholinergic motoneuronal inputs to R-interneurons or the GABAergic outputs from R-interneurons to other interneurons. Whole-cell recording from R-interneurons and imaging of calcium dye-labeled interneurons established that R-interneuron cell bodies were located dorsomedial to the lateral motor column (R-interneuron region). This region became active before other labeled interneurons when an episode was triggered by motor axon stimulation. At the beginning of a spontaneous episode, whole-cell recordings revealed that R-interneurons fired a high-frequency burst of spikes and optical recordings demonstrated that the R-interneuron region became active before other labeled interneurons. In the presence of cholinergic blockade, however, episode initiation slowed and the inter-episode interval lengthened. In addition, optical activity recorded from the R-interneuron region no longer led that of other labeled interneurons. Instead the initial activity occurred bilaterally in the region medial to the motor column and encompassing the central canal. These findings are consistent with the hypothesis that transient depolarizations and firing in motoneurons, originating from random fluctuations of interneuronal synaptic activity, activate R-interneurons, which then trigger the recruitment of the rest of the spinal interneuronal network. This unusual function for R-interneurons is likely to arise because the output of these interneurons is functionally excitatory during development. JF - Journal of neurophysiology AU - Wenner, P AU - O'Donovan, M J AD - Laboratory of Neural Control, Section on Developmental Neurobiology, National Institute of Neurological Disorders and Stroke/NIH, 49 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1481 EP - 1498 VL - 86 IS - 3 SN - 0022-3077, 0022-3077 KW - Fluorescent Dyes KW - 0 KW - GABA Antagonists KW - Ganglionic Blockers KW - Glycine Agents KW - Muscarinic Antagonists KW - Organic Chemicals KW - calcium green KW - 138067-55-7 KW - Mecamylamine KW - 6EE945D3OK KW - Atropine KW - 7C0697DR9I KW - Strychnine KW - H9Y79VD43J KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Action Potentials -- physiology KW - Animals KW - Chick Embryo KW - Mecamylamine -- pharmacology KW - Action Potentials -- drug effects KW - GABA Antagonists -- pharmacology KW - Patch-Clamp Techniques KW - Ganglionic Blockers -- pharmacology KW - Muscarinic Antagonists -- pharmacology KW - Spinal Nerve Roots -- physiology KW - Strychnine -- pharmacology KW - Glycine Agents -- pharmacology KW - Atropine -- pharmacology KW - Motor Neurons -- physiology KW - Neural Pathways -- physiology KW - Interneurons -- physiology KW - Interneurons -- cytology KW - Motor Neurons -- cytology KW - Spinal Cord -- embryology KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71144310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Mechanisms+that+initiate+spontaneous+network+activity+in+the+developing+chick+spinal+cord.&rft.au=Wenner%2C+P%3BO%27Donovan%2C+M+J&rft.aulast=Wenner&rft.aufirst=P&rft.date=2001-09-01&rft.volume=86&rft.issue=3&rft.spage=1481&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-linked carbohydrates in tyrosinase are required for its recognition by human MHC class II-restricted CD4(+) T cells. AN - 71144157; 11536167 AB - Glycosylation of mammalian proteins is known to influence their intracellular trafficking, half life, and susceptibility to enzymatic degradation. Rare instances of natural T cell epitopes dependent upon glycosylation for recognition have been described. We report here on human CD4(+) T lymphocyte cultures and clones from two melanoma patients that recognize the melanoma-associated Ag tyrosinase in the context of HLA-DR4 and -DR8. These T cells recognize tyrosinase, normally a heavily glycosylated molecule, when expressed constitutively in melanoma cells or in COS-7 transfectants pulsed as lysates onto autologous APC. However, these T cells fail to recognize tyrosinase expressed in bacteria, nor do they react with overlapping peptides covering full-length tyrosinase, suggesting a critical role for glycosylation in the processing and / or composition of the stimulatory epitopes. The requirement for glycosylation was demonstrated by the failure of tyrosinase-specific CD4(+) T cells to recognize tyrosinase synthesized in the presence of glycosylation inhibitors, or deglycosylated enzymatically. Site-directed mutagenesis of each of seven potential N-glycosylation sites showed that four sites were required to generate forms of tyrosinase that could be recognized by individual T cell clones. These data indicate that certain carbohydrate moieties are required for processing the tyrosinase peptides recognized by CD4(+) T cells. Post-translational modifications of human tumor-associated proteins such as tyrosinase could be a critical factor for the development of antitumor immune responses. JF - European journal of immunology AU - Housseau, F AU - Moorthy, A AU - Langer, D A AU - Robbins, P F AU - Gonzales, M I AU - Topalian, S L AD - The Surgery Branch, Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 2690 EP - 2701 VL - 31 IS - 9 SN - 0014-2980, 0014-2980 KW - Antigens, Neoplasm KW - 0 KW - Carbohydrates KW - Epitopes, T-Lymphocyte KW - Glycoproteins KW - Histocompatibility Antigens Class II KW - Monophenol Monooxygenase KW - EC 1.14.18.1 KW - Index Medicus KW - Clone Cells KW - Animals KW - COS Cells KW - Glycoproteins -- biosynthesis KW - Humans KW - Epitopes, T-Lymphocyte -- immunology KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Antigens, Neoplasm -- chemistry KW - Antigens, Neoplasm -- genetics KW - Antigens, Neoplasm -- immunology KW - Cell Line KW - Epitopes, T-Lymphocyte -- chemistry KW - Monophenol Monooxygenase -- immunology KW - Monophenol Monooxygenase -- chemistry KW - CD4-Positive T-Lymphocytes -- immunology KW - Histocompatibility Antigens Class II -- immunology KW - Monophenol Monooxygenase -- genetics KW - Melanoma -- immunology KW - Carbohydrates -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71144157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=N-linked+carbohydrates+in+tyrosinase+are+required+for+its+recognition+by+human+MHC+class+II-restricted+CD4%28%2B%29+T+cells.&rft.au=Housseau%2C+F%3BMoorthy%2C+A%3BLanger%2C+D+A%3BRobbins%2C+P+F%3BGonzales%2C+M+I%3BTopalian%2C+S+L&rft.aulast=Housseau&rft.aufirst=F&rft.date=2001-09-01&rft.volume=31&rft.issue=9&rft.spage=2690&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electrophysiological evidence for vasopressin V(1) receptors on neonatal motoneurons, premotor and other ventral horn neurons. AN - 71142177; 11535670 AB - Prominent arginine-vasopressin (AVP) binding and AVP V(1) type receptors are expressed early in the developing rat spinal cord. We sought to characterize their influence on neural excitability by using patch-clamp techniques to record AVP-induced responses from a population of motoneurons and interneurons in neonatal (5-18 days) rat spinal cord slices. Data were obtained from 58 thoracolumbar (T(7)-L(5)) motoneurons and 166 local interneurons. A majority (>90%) of neurons responded to bath applied AVP (10 nM to 3 microM) and (Phe(2), Orn(8))-vasotocin, a V(1) receptor agonist, but not V(2) or oxytocin receptor agonists. In voltage-clamp, postsynaptic responses in motoneurons were characterized by slowly rising, prolonged (7-10 min) and tetrodotoxin-resistant inward currents associated with a 25% reduction in a membrane potassium conductance that reversed near -100 mV. In interneurons, net AVP-induced inward currents displayed three patterns: decreasing membrane conductance with reversal near -100 mV, i.e., similar to that in motoneurons (24 cells); increasing conductance with reversal near -40 mV (21 cells); small reduction in conductance with no reversal within the current range tested (41 cells). A presynaptic component recorded in most neurons was evident as an increase in the frequency but not amplitude (in motoneurons) of inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs), in large part due to AVP-induced firing in inhibitory (mainly glycinergic) and excitatory (glutamatergic) neurons synapsing on the recorded cells. An increase in frequency but not amplitude of miniature IPSCs and EPSCs also indicated an AVP enhancement of neurotransmitter release from axon terminals of inhibitory and excitatory interneurons. These observations provide support for a broad presynaptic and postsynaptic distribution of AVP V(1) type receptors and indicate that their activation can enhance the excitability of a majority of neurons in neonatal ventral spinal cord. JF - Journal of neurophysiology AU - Oz, M AU - Kolaj, M AU - Renaud, L P AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1202 EP - 1210 VL - 86 IS - 3 SN - 0022-3077, 0022-3077 KW - Excitatory Amino Acid Antagonists KW - 0 KW - GABA Antagonists KW - Glycine Agents KW - Hormone Antagonists KW - Quinoxalines KW - Receptors, Vasopressin KW - vasotocin, Phe(2)-Orn(8)- KW - Arginine Vasopressin KW - 113-79-1 KW - 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline KW - 118876-58-7 KW - Oxytocin KW - 50-56-6 KW - oxytocin, Thr(4)-Gly(7)- KW - 60786-59-6 KW - vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine- KW - 73168-24-8 KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Hemosiderin KW - 9011-92-1 KW - Deamino Arginine Vasopressin KW - ENR1LLB0FP KW - Strychnine KW - H9Y79VD43J KW - Vasotocin KW - W6S6URY8OF KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Deamino Arginine Vasopressin -- pharmacology KW - GABA Antagonists -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Excitatory Postsynaptic Potentials -- drug effects KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Interneurons -- physiology KW - Strychnine -- pharmacology KW - Glycine Agents -- pharmacology KW - Hemosiderin -- pharmacology KW - Quinoxalines -- pharmacology KW - Male KW - Excitatory Postsynaptic Potentials -- physiology KW - Female KW - Hormone Antagonists -- pharmacology KW - Arginine Vasopressin -- pharmacology KW - Arginine Vasopressin -- analogs & derivatives KW - Vasotocin -- pharmacology KW - Vasotocin -- analogs & derivatives KW - Receptors, Vasopressin -- physiology KW - Anterior Horn Cells -- physiology KW - Oxytocin -- analogs & derivatives KW - Oxytocin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71142177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Electrophysiological+evidence+for+vasopressin+V%281%29+receptors+on+neonatal+motoneurons%2C+premotor+and+other+ventral+horn+neurons.&rft.au=Oz%2C+M%3BKolaj%2C+M%3BRenaud%2C+L+P&rft.aulast=Oz&rft.aufirst=M&rft.date=2001-09-01&rft.volume=86&rft.issue=3&rft.spage=1202&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing actions of protein kinase A and C mediate Hebbian synaptic plasticity. AN - 71132746; 11528415 AB - A compartmental nerve-muscle tissue culture system expresses Hebbian activity-dependent synapse modulation. Protein kinase C (PKC) mediates a heterosynaptic loss of efficacy, and we now show that protein kinase A (PKA) is involved in homosynaptic stabilization. Both work through postsynaptic changes in the acetylcholine receptor (AChR) as measured electrophysiologically and by imaging techniques. JF - Nature neuroscience AU - Li, M X AU - Jia, M AU - Jiang, H AU - Dunlap, V AU - Nelson, P G AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, Building 49, Room 5A38, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 871 EP - 872 VL - 4 IS - 9 SN - 1097-6256, 1097-6256 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Enzyme Activation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Electric Stimulation KW - Synapses -- physiology KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Neuronal Plasticity -- physiology KW - Protein Kinase C -- physiology KW - Models, Neurological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71132746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+neuroscience&rft.atitle=Opposing+actions+of+protein+kinase+A+and+C+mediate+Hebbian+synaptic+plasticity.&rft.au=Li%2C+M+X%3BJia%2C+M%3BJiang%2C+H%3BDunlap%2C+V%3BNelson%2C+P+G&rft.aulast=Li&rft.aufirst=M&rft.date=2001-09-01&rft.volume=4&rft.issue=9&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Nature+neuroscience&rft.issn=10976256&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits. AN - 71132359; 11529691 AB - This study has been initiated to investigate, in hypercholesterolaemic rabbits, whether L-carnitine deficiency could be an additional risk factor in atherosclerosis, and if so, whether L-carnitine supplementation could prevent the progression of atherosclerosis. Hypercholesterolaemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days, whereas, carnitine deficiency was induced by daily i.p. administration of 250 mg kg(-1) of D-carnitine for 28 days. Histopathological examination of aorta and coronaries from hypercholesterolaemic rabbits revealed severe atherosclerotic lesions, intimal plaques and foam cell formation. Also, hypercholesterolaemic diet resulted in a significant 53 and 43% decrease in reduced glutathion (GSH) levels and a significant (1.87-fold) and (14.1-fold) increase in malonedialdhyde (MDA) levels in aorta and cardiac tissues, respectively. Daily administration of L-carnitine (250 mg kg(-1)) for 28 days, completely prevented the progression of atherosclerotic lesions induced by hpercholesterolaemia in both aorta and coronaries. Conversely, daily administration of D-carnitine (250 mg kg(-1)) for 28 days increased the progression of atherosclerotic lesions with the appearance of foam cells and apparent intimal plaques which are even larger than that seen in hypercholesterolaemic rabbits. Both L-carnitine and D-carnitine produced similar effects on the lipid profile, GSH and MDA which may point to the conclusion that: (1) L-carnitine prevents the progression of atherosclerotic lesions by another mechanism in addition to its antioxidant and lipid-lowering effects; (2) endogenous carnitine depletion and/or carnitine deficiency should be viewed as an additional risk factor in atherogenesis. Copyright 2001 Academic Press. JF - Pharmacological research AU - Sayed-Ahmed, M M AU - Khattab, M M AU - Gad, M Z AU - Mostafa, N AD - Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt. mmsayedahmed@hotmail.com Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 235 EP - 242 VL - 44 IS - 3 SN - 1043-6618, 1043-6618 KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - Animals KW - Aorta, Thoracic -- drug effects KW - Risk Factors KW - Rabbits KW - Coronary Vessels -- pathology KW - Coronary Vessels -- drug effects KW - Aorta, Thoracic -- pathology KW - Male KW - Carnitine -- deficiency KW - Carnitine -- pharmacology KW - Hypercholesterolemia -- pathology KW - Hypercholesterolemia -- chemically induced KW - Carnitine -- therapeutic use KW - Arteriosclerosis -- prevention & control KW - Arteriosclerosis -- pathology KW - Hypercholesterolemia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71132359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=L-carnitine+prevents+the+progression+of+atherosclerotic+lesions+in+hypercholesterolaemic+rabbits.&rft.au=Sayed-Ahmed%2C+M+M%3BKhattab%2C+M+M%3BGad%2C+M+Z%3BMostafa%2C+N&rft.aulast=Sayed-Ahmed&rft.aufirst=M&rft.date=2001-09-01&rft.volume=44&rft.issue=3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=10436618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung. AN - 71124017; 11522624 AB - p53 mutations are common in lung cancer. In smoking-associated lung cancer,the occurrence of G:C to T:A transversions at hotspot codons, e.g., 157, 248, 249,and 273, has been linked to the presence of carcinogenic chemicalsin tobacco smoke including polycyclic aromatic hydrocarbons suchas benzo(a)pyrene (BP). In the present study, we have used a highly sensitive mutation assay to determine the p53 mutation load in nontumorous human lung and to study the mutability of p53 codons 157, 248, 249, and 250 to benzo(a)pyrene-diol-epoxide (BPDE), an active metabolite of BP in human bronchial epithelial BEAS-2B cells. We determined the p53 mutational load at codons 157, 248, 249, and 250 in nontumorous peripheral lung tissue either from lung cancer cases among smokers or noncancer controls among smokers and nonsmokers. A 5-25-fold higher frequency of GTC(val) to TTC(phe) transversions at codon 157 was found in nontumorous samples (57%) from cancer cases (n = 14) when compared with noncancer controls (n = 8; P < 0.01). Fifty percent (7/14) of the nontumorous samples from lung cancer cases showed a high frequency of codon 249 AGG(arg) to AGT(ser) mutations (P < 0.02). Four of these seven samples with AGT(ser) mutations also showed a high frequency of codon 249 AGG(arg) to ATG(met) mutations, whereas only one sample showed a codon 250 CCC to ACC transversion. Tumor tissue from these lung cancer cases (38%) contained p53 mutations but were different from the above mutations found in the nontumorous pair. Noncancer control samples from smokers or nonsmokers did not contain any detectable mutations at codons 248, 249, or 250. BEAS-2B bronchial epithelial cells exposed to doses of 0.125, 0.5, and 1.0 microM BPDE, showed G:C to T:A transversions at codon 157 at a frequency of 3.5 x 10(-7), 4.4 x 10(-7), and 8.9 x 10(-7), respectively. No mutations at codon 157 were found in the DMSO-treated controls. These doses of BPDE induced higher frequencies, ranging from 4-12-fold, of G:C to T:A transversions at codon 248, G:C to T:A transversions and G:C to A:T transitions at codon 249, and C:G to T:A transitions at codon 250 when compared with the DMSO-treated controls. These data are consistent with the hypothesis that chemical carcinogens such as BP in cigarette smoke cause G:C to T:A transversions at p53 codons 157, 248, and 249 and that nontumorous lung tissues from smokers with lung cancer carry a high p53 mutational load at these codons. JF - Cancer research AU - Hussain, S P AU - Amstad, P AU - Raja, K AU - Sawyer, M AU - Hofseth, L AU - Shields, P G AU - Hewer, A AU - Phillips, D H AU - Ryberg, D AU - Haugen, A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 6350 EP - 6355 VL - 61 IS - 17 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Codon KW - Mutagens KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Index Medicus KW - Codon -- genetics KW - Humans KW - Carcinogens -- toxicity KW - Smoking -- adverse effects KW - Aged KW - Child KW - Smoking -- genetics KW - Child, Preschool KW - Infant KW - Codon -- drug effects KW - Cells, Cultured KW - Adult KW - Lung Neoplasms -- genetics KW - Middle Aged KW - Lung Neoplasms -- chemically induced KW - Adolescent KW - Mutation KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- toxicity KW - Genes, p53 -- drug effects KW - Mutagenesis, Site-Directed -- genetics KW - Genes, p53 -- genetics KW - Lung -- drug effects KW - Mutagens -- toxicity KW - Lung -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71124017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Mutability+of+p53+hotspot+codons+to+benzo%28a%29pyrene+diol+epoxide+%28BPDE%29+and+the+frequency+of+p53+mutations+in+nontumorous+human+lung.&rft.au=Hussain%2C+S+P%3BAmstad%2C+P%3BRaja%2C+K%3BSawyer%2C+M%3BHofseth%2C+L%3BShields%2C+P+G%3BHewer%2C+A%3BPhillips%2C+D+H%3BRyberg%2C+D%3BHaugen%2C+A%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2001-09-01&rft.volume=61&rft.issue=17&rft.spage=6350&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo extracellular recording of striatal neurons in the awake rat following unilateral 6-hydroxydopamine lesions. AN - 71117569; 11520122 AB - The purpose of this study was to further understand the functional effects of dopaminergic input to the dorsal striatum and to compare the effects of dopaminergic lesions in awake and anesthetized animals. We examined the effects of unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic bundle on the firing properties of dorsal striatal neurons in the awake freely moving rat using chronically implanted microwire electrode arrays. We recorded extracellular activity of striatal neurons under baseline conditions and following the systemic injection of apomorphine in awake and anesthetized subjects. Firing rates were higher in the hemisphere ipsilateral to the 6-OHDA lesion compared to rates of neurons from the contralateral unlesioned hemisphere. Striatal firing rates from sham and no-surgery control rats were, in general, higher than those from the contralateral unlesioned striatum of experimental subjects. Apomorphine (0.05 mg/kg, sc) normalized the differences in firing rates in lesioned animals by increasing firing of neurons within the contralateral unlesioned side, while simultaneously decreasing firing of neurons within the ipsilateral lesioned side. Mean firing rates were substantially higher in awake animals than in subjects anesthetized with chloral hydrate, perhaps reflecting anesthesia-induced decreases in excitatory input to striatal neurons. Chloral hydrate anesthesia decreased firing rates of neurons in the lesioned, unlesioned, and control striata to a similar degree, although absolute firing rates of neurons from the 6-OHDA-lesioned striata remained elevated over all other groups. Unilateral 6-OHDA lesions also altered the pattern of spike output in the awake animal as indicated by an increase in the number of bursts per minute following dopaminergic deafferentation. This and other burst parameters were altered by apomorphine. Our findings show that effects of dopaminergic deafferentation can be measured in the awake behaving animal; this model should prove useful for testing the behavioral and functional effects of experimental manipulations designed to reduce or reverse the effects of dopaminergic cell loss. In addition, these results suggest that the contralateral changes in striatal function which occur in the unilateral dopaminergic lesion model should be considered when evaluating experimental results. Copyright 2001 Academic Press. JF - Experimental neurology AU - Chen, M T AU - Morales, M AU - Woodward, D J AU - Hoffer, B J AU - Janak, P H AD - Intramural Research Program, Cellular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, Maryland, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 72 EP - 83 VL - 171 IS - 1 SN - 0014-4886, 0014-4886 KW - Receptors, Dopamine D2 KW - 0 KW - Chloral Hydrate KW - 418M5916WG KW - Oxidopamine KW - 8HW4YBZ748 KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Dopamine -- pharmacology KW - Electrodes, Implanted KW - Apomorphine -- pharmacology KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Action Potentials -- drug effects KW - Chloral Hydrate -- pharmacology KW - Rats KW - Rats, Inbred F344 KW - Anesthesia KW - Receptors, Dopamine D2 -- agonists KW - Motor Activity -- drug effects KW - Wakefulness KW - Male KW - Microelectrodes KW - Parkinson Disease, Secondary -- physiopathology KW - Parkinson Disease, Secondary -- chemically induced KW - Parkinson Disease, Secondary -- pathology KW - Corpus Striatum -- physiopathology KW - Neurons -- drug effects KW - Neurons -- physiology KW - Corpus Striatum -- drug effects KW - Corpus Striatum -- pathology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71117569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=In+vivo+extracellular+recording+of+striatal+neurons+in+the+awake+rat+following+unilateral+6-hydroxydopamine+lesions.&rft.au=Chen%2C+M+T%3BMorales%2C+M%3BWoodward%2C+D+J%3BHoffer%2C+B+J%3BJanak%2C+P+H&rft.aulast=Chen&rft.aufirst=M&rft.date=2001-09-01&rft.volume=109&rft.issue=9&rft.spage=881&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Persistent organic pollutants in children. AN - 71116530; 11518817 JF - Pediatric research AU - Longnecker, M P AU - Rogan, W J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 322 EP - 323 VL - 50 IS - 3 SN - 0031-3998, 0031-3998 KW - Environmental Pollutants KW - 0 KW - Hydrocarbons, Cyclic KW - Hydrocarbons, Halogenated KW - Index Medicus KW - Infant KW - Breast Feeding -- adverse effects KW - Milk, Human -- chemistry KW - Humans KW - Infant, Newborn KW - Child KW - Diet KW - Body Mass Index KW - Child, Preschool KW - Environmental Pollutants -- metabolism KW - Hydrocarbons, Cyclic -- adverse effects KW - Hydrocarbons, Halogenated -- blood KW - Hydrocarbons, Halogenated -- adverse effects KW - Hydrocarbons, Cyclic -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71116530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+research&rft.atitle=Persistent+organic+pollutants+in+children.&rft.au=Longnecker%2C+M+P%3BRogan%2C+W+J&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2001-09-01&rft.volume=50&rft.issue=3&rft.spage=322&rft.isbn=&rft.btitle=&rft.title=Pediatric+research&rft.issn=00313998&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-08-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Pediatr Res. 2001 Sep;50(3):331-6 [11518819] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nociceptor sensitization by extracellular signal-regulated kinases. AN - 71115421; 11517280 AB - Inflammatory pain, characterized by a decrease in mechanical nociceptive threshold (hyperalgesia), arises through actions of inflammatory mediators, many of which sensitize primary afferent nociceptors via G-protein-coupled receptors. Two signaling pathways, one involving protein kinase A (PKA) and one involving the epsilon isozyme of protein kinase C (PKCepsilon), have been implicated in primary afferent nociceptor sensitization. Here we describe a third, independent pathway that involves activation of extracellular signal-regulated kinases (ERKs) 1 and 2. Epinephrine, which induces hyperalgesia by direct action at beta(2)-adrenergic receptors on primary afferent nociceptors, stimulated phosphorylation of ERK1/2 in cultured rat dorsal root ganglion cells. This was inhibited by a beta(2)-adrenergic receptor blocker and by an inhibitor of mitogen and extracellular signal-regulated kinase kinase (MEK), which phosphorylates and activates ERK1/2. Inhibitors of G(i/o)-proteins, Ras farnesyltransferases, and MEK decreased epinephrine-induced hyper-algesia. In a similar manner, phosphorylation of ERK1/2 was also decreased by these inhibitors. Local injection of dominant active MEK produced hyperalgesia that was unaffected by PKA or PKCepsilon inhibitors. Conversely, hyperalgesia produced by agents that activate PKA or PKCepsilon was unaffected by MEK inhibitors. We conclude that a Ras-MEK-ERK1/2 cascade acts independent of PKA or PKCepsilon as a novel signaling pathway for the production of inflammatory pain. This pathway may present a target for a new class of analgesic agents. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Aley, K O AU - Martin, A AU - McMahon, T AU - Mok, J AU - Levine, J D AU - Messing, R O AD - Departments of Medicine and Oral Surgery, National Institutes of Health Pain Center at the University of California, San Francisco, San Francisco, California 94143, USA. Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 6933 EP - 6939 VL - 21 IS - 17 KW - Adrenergic beta-2 Receptor Antagonists KW - 0 KW - Enzyme Inhibitors KW - Isoenzymes KW - Receptors, Adrenergic, beta-2 KW - Prkce protein, mouse KW - EC 2.7.1.- KW - Prkce protein, rat KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-epsilon KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Heterotrimeric GTP-Binding Proteins KW - EC 3.6.5.1 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Neurons -- drug effects KW - Pain Measurement KW - Isoenzymes -- metabolism KW - Rats KW - Ganglia, Spinal -- physiopathology KW - Enzyme Activation -- drug effects KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Heterotrimeric GTP-Binding Proteins -- metabolism KW - Ganglia, Spinal -- drug effects KW - Heterotrimeric GTP-Binding Proteins -- antagonists & inhibitors KW - Male KW - Neurons -- metabolism KW - Dose-Response Relationship, Drug KW - Mice KW - Phosphorylation -- drug effects KW - Protein Kinase C -- metabolism KW - Ganglia, Spinal -- cytology KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Signal Transduction -- drug effects KW - Neurons -- cytology KW - Enzyme Inhibitors -- pharmacology KW - Crosses, Genetic KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - ras Proteins -- metabolism KW - Receptors, Adrenergic, beta-2 -- metabolism KW - Nociceptors -- physiopathology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Hyperalgesia -- physiopathology KW - Hyperalgesia -- chemically induced KW - Nociceptors -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71115421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Nociceptor+sensitization+by+extracellular+signal-regulated+kinases.&rft.au=Aley%2C+K+O%3BMartin%2C+A%3BMcMahon%2C+T%3BMok%2C+J%3BLevine%2C+J+D%3BMessing%2C+R+O&rft.aulast=Aley&rft.aufirst=K&rft.date=2001-09-01&rft.volume=21&rft.issue=17&rft.spage=6933&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - E2-induced degradation of uterine insulin receptor substrate-2: requirement for an IGF-I-stimulated, proteasome-dependent pathway. AN - 71110350; 11517161 AB - The insulin receptor substrates are docking proteins that bind various receptor tyrosine kinases and signaling proteins. Previous studies have shown that E2 or progesterone can regulate the relative abundance of insulin receptor substrate-1 and -2 in cells and tissues. For instance, uterine insulin receptor substrate-2 was decreased markedly at 24 h after E2 treatment of mice. In the present study we used various in vivo experimental approaches to examine the mechanism by which E2 influences uterine insulin receptor substrate-2 expression. Uterine insulin receptor substrate-2 mRNA levels were diminished after E2 treatment, but this diminution did not account for the total reduction in insulin receptor substrate-2 protein, suggesting that the E2-induced decrease in insulin receptor substrate-2 is not regulated solely at the mRNA level. Cotreatment with progesterone prevented the E2-stimulated reduction in insulin receptor substrate-2 protein at 24 h after hormone exposure. In addition, MG-132 and epoxomicin, inhibitors of proteasomal protease activity, inhibited the E2-induced decrease in uterine insulin receptor substrate-2 protein levels, and this correlated to an increase in uterine protein ubiquitination. Insulin receptor substrate-2 protein was diminished in uteri of E2-treated insulin receptor substrate-1-null mutant mice, but not in E2-treated IGF-I-null mutant mice. Furthermore, E2-induced diminution of uterine insulin receptor substrate-2 protein was only partially inhibited in the presence of wortmannin, a PI3K inhibitor. Collectively, these data suggest that the E2-induced decrease in uterine insulin receptor substrate-2 requires IGF-I signaling, is not dependent solely on insulin receptor substrate-1 and PI3K, and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity. We speculate that the IGF-I-activated IGF-I receptor, in response to E2, directly or indirectly modifies insulin receptor substrate-2, probably through phosphorylation, leading to ubiquitination and subsequent degradation of this docking protein by the proteasome. This degradation could be a regulatory step to inhibit insulin receptor substrate-2-dependent signaling in the uterus. JF - Endocrinology AU - Richards, R G AU - Klotz, D M AU - Bush, M R AU - Walmer, D K AU - DiAugustine, R P AD - Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 3842 EP - 3849 VL - 142 IS - 9 SN - 0013-7227, 0013-7227 KW - Androstadienes KW - 0 KW - IRS2 protein, human KW - Insulin Receptor Substrate Proteins KW - Intracellular Signaling Peptides and Proteins KW - Irs2 protein, mouse KW - Multienzyme Complexes KW - Phosphodiesterase Inhibitors KW - Phosphoproteins KW - Proteins KW - RNA, Messenger KW - Ubiquitins KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - wortmannin KW - XVA4O219QW KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Phosphodiesterase Inhibitors -- pharmacology KW - Reference Values KW - Progesterone -- pharmacology KW - Humans KW - Androstadienes -- pharmacology KW - Mice KW - Proteins -- metabolism KW - Mice, Inbred Strains KW - Estrus -- physiology KW - Ubiquitins -- metabolism KW - RNA, Messenger -- metabolism KW - Mice, Knockout -- genetics KW - Ovary -- physiology KW - Female KW - Uterus -- metabolism KW - Insulin-Like Growth Factor I -- genetics KW - Phosphoproteins -- deficiency KW - Insulin-Like Growth Factor I -- physiology KW - Phosphoproteins -- genetics KW - Insulin-Like Growth Factor I -- deficiency KW - Cysteine Endopeptidases -- physiology KW - Estradiol -- pharmacology KW - Multienzyme Complexes -- physiology KW - Phosphoproteins -- antagonists & inhibitors KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71110350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=E2-induced+degradation+of+uterine+insulin+receptor+substrate-2%3A+requirement+for+an+IGF-I-stimulated%2C+proteasome-dependent+pathway.&rft.au=Richards%2C+R+G%3BKlotz%2C+D+M%3BBush%2C+M+R%3BWalmer%2C+D+K%3BDiAugustine%2C+R+P&rft.aulast=Richards&rft.aufirst=R&rft.date=2001-09-01&rft.volume=142&rft.issue=9&rft.spage=3842&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fibrinogen induces IL-8 synthesis in human neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine or leukotriene B(4). AN - 71106500; 11509634 AB - Human exudative neutrophils have greatly increased stores of the neutrophil chemoattractant IL-8 compared with peripheral blood cells, but the mechanism for the increase is not defined. In this report, we show that treatment of peripheral blood neutrophils with the chemotactic peptide fMLP or with leukotriene B(4) or fibrinogen results in little increase in the production of IL-8 by peripheral blood neutrophils. However, a chemotactically active dose of fMLP (5 x 10(-9) M) or leukotriene B(4) (1 x 10(-7) M) in the presence of a physiological concentration (2 mg/ml) of fibrinogen results in a receptor-mediated, pertussis toxin-sensitive, synergistic 30-fold increase in IL-8 synthesis. The levels of IL-8 attained are comparable to those observed in exudative cells. Higher concentrations of fMLP (1 x 10(-7) M) are associated with reduced IL-8 protein synthesis without IL-8 degradation, indicating a sensitive regulatory mechanism for IL-8 production. Treatment of neutrophils with fibrinogen and fMLP resulted in minimal changes in the steady state levels of mRNA for macrophage inflammatory protein-1alpha and -1beta and monocyte chemoattractant protein-1. In contrast, in the presence of fibrinogen, the steady-state level of neutrophil IL-8 mRNA increased 8-fold with 5 x 10(-9) M fMLP but was not decreased with 1 x 10(-7) M fMLP, suggesting that neutrophils are specifically adapted to modulate neutrophil IL-8 synthesis through transcriptional and posttranscriptional mechanisms. The data indicate that fibrinogen can function not only as a substrate in the clotting cascade, but also as an important effector during the evolution of the innate immune response. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kuhns, D B AU - Nelson, E L AU - Alvord, W G AU - Gallin, J I AD - Clinical Services Program, SAIC Frederick, and Data Management Services, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 2869 EP - 2878 VL - 167 IS - 5 SN - 0022-1767, 0022-1767 KW - Chemokine CCL2 KW - 0 KW - Chemokine CCL4 KW - Interleukin-8 KW - Macrophage Inflammatory Proteins KW - Protein Synthesis Inhibitors KW - RNA, Messenger KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Leukotriene B4 KW - Receptors, Peptide KW - Virulence Factors, Bordetella KW - Leukotriene B4 KW - 1HGW4DR56D KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Fibrinogen KW - 9001-32-5 KW - Cycloheximide KW - 98600C0908 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Leukotriene B4 -- metabolism KW - Receptors, Peptide -- metabolism KW - Humans KW - Leukotriene B4 -- pharmacology KW - Leukocyte-Adhesion Deficiency Syndrome -- immunology KW - RNA, Messenger -- genetics KW - Calcium -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Receptors, Immunologic -- drug effects KW - Cycloheximide -- pharmacology KW - Receptors, Immunologic -- metabolism KW - In Vitro Techniques KW - N-Formylmethionine Leucyl-Phenylalanine -- administration & dosage KW - Drug Synergism KW - Chemokine CCL2 -- genetics KW - Macrophage Inflammatory Proteins -- genetics KW - Dose-Response Relationship, Drug KW - Leukotriene B4 -- administration & dosage KW - Receptors, Leukotriene B4 -- drug effects KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Receptors, Peptide -- drug effects KW - Protein Synthesis Inhibitors -- pharmacology KW - RNA, Messenger -- metabolism KW - Neutrophils -- drug effects KW - Interleukin-8 -- biosynthesis KW - Neutrophils -- immunology KW - Interleukin-8 -- genetics KW - Fibrinogen -- pharmacology KW - Neutrophils -- physiology KW - Fibrinogen -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71106500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Fibrinogen+induces+IL-8+synthesis+in+human+neutrophils+stimulated+with+formyl-methionyl-leucyl-phenylalanine+or+leukotriene+B%284%29.&rft.au=Kuhns%2C+D+B%3BNelson%2C+E+L%3BAlvord%2C+W+G%3BGallin%2C+J+I&rft.aulast=Kuhns&rft.aufirst=D&rft.date=2001-09-01&rft.volume=167&rft.issue=5&rft.spage=2869&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parental occupational exposures to electromagnetic fields and radiation and the incidence of neuroblastoma in offspring. AN - 71096623; 11505168 AB - We examined parental occupational exposures to electromagnetic fields and radiation and the incidence of neuroblastoma in offspring. Cases were 538 children diagnosed with neuroblastoma between 1992 and 1994 in the United States or Canada. Age-matched controls were selected by random-digit dialing. Occupational exposures to electrical equipment and radiation sources were classified by an industrial hygienist, and average exposures to extremely low frequency magnetic fields were estimated using a job exposure matrix. Maternal exposure to a broad grouping of sources that produce radiofrequency radiation was associated with an increased incidence of neuroblastoma (odds ratio = 2.8; 95% confidence interval = 0.9-8.7). Paternal exposure to battery-powered forklifts was positively associated with neuroblastoma (odds ratio = 1.6; 95% confidence interval = 0.8-3.2), as were some types of equipment that emit radiofrequency radiation (odds ratios congruent with 2.0); however, the broad groupings of sources that produce ELF fields, radiofrequency radiation, or ionizing radiation were not associated with neuroblastoma. Paternal average extremely low frequency magnetic field exposure >0.4 microTesla was weakly associated with neuroblastoma (odds ratio = 1.6; 95% confidence interval = 0.9-2.8), whereas maternal exposure was not. Overall, there was scant supportive evidence of strong associations between parental exposures in electromagnetic spectrum and neuroblastoma in offspring. JF - Epidemiology (Cambridge, Mass.) AU - De Roos, A J AU - Teschke, K AU - Savitz, D A AU - Poole, C AU - Grufferman, S AU - Pollock, B H AU - Olshan, A F AD - Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA. deroosa@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 508 EP - 517 VL - 12 IS - 5 SN - 1044-3983, 1044-3983 KW - Index Medicus KW - Humans KW - Infant, Newborn KW - Case-Control Studies KW - Incidence KW - United States -- epidemiology KW - Maternal Exposure KW - Male KW - Female KW - Pregnancy KW - Occupational Exposure KW - Paternal Exposure KW - Radiation KW - Neuroblastoma -- etiology KW - Neuroblastoma -- epidemiology KW - Electromagnetic Fields -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71096623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Parental+occupational+exposures+to+electromagnetic+fields+and+radiation+and+the+incidence+of+neuroblastoma+in+offspring.&rft.au=De+Roos%2C+A+J%3BTeschke%2C+K%3BSavitz%2C+D+A%3BPoole%2C+C%3BGrufferman%2C+S%3BPollock%2C+B+H%3BOlshan%2C+A+F&rft.aulast=De+Roos&rft.aufirst=A&rft.date=2001-09-01&rft.volume=12&rft.issue=5&rft.spage=508&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Femtomolar concentrations of dynorphins protect rat mesencephalic dopaminergic neurons against inflammatory damage. AN - 71094960; 11504811 AB - The hallmark of Parkinson's disease is the death of nigral dopaminergic neurons, and inflammation in the brain has been increasingly associated with the pathogenesis of this neurological disorder. Dynorphins are among the major opioid peptides in the striato-nigral pathway and are important in regulating dopaminergic neuronal activities. However, it is not clear whether dynorphins play a role in the survival of nigral dopaminergic neurons. We have recently demonstrated that lipopolysaccharide (LPS) activates the brain immune cells microglia, in vitro and in vivo, to release neurotoxic factors to degenerate dopaminergic neurons. The purpose of this study was to explore the neuroprotective effect of dynorphins in the inflammation-mediated degeneration of dopaminergic neurons in rat midbrain neuron-glia cultures. LPS-induced neurotoxicity was significantly reduced by treatment with ultra low concentrations (10(-13)--10(-15) M) of the kappa-opioid receptor agonist dynorphin A (1--17) or the receptor binding ineffective [des-Tyr(1)]dynorphin A (2--17), but not by U50488, a synthetic kappa-receptor agonist. The glia-mediated neuroprotective effect of dynorphins was further supported by the finding that femtomolar concentrations of dynorphins did not prevent the killing of dopaminergic neurons by 6-hydroxydopamine. However, ultra low concentrations of dynorphins inhibited LPS-induced production of superoxide. These results suggest a glia-mediated and conventional opioid receptor-unrelated mechanism of action for the neuroprotective effect of ultra low concentrations of dynorphins. Understanding the underlying mechanisms of action should further define the roles of dynorphins in the regulation of dopaminergic neurons and help devise novel strategies to combat neurodegenerative diseases. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, B AU - Qin, L AU - Yang, S N AU - Wilson, B C AU - Liu, Y AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. liu3@niehs.nih.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 1133 EP - 1141 VL - 298 IS - 3 SN - 0022-3565, 0022-3565 KW - Lipopolysaccharides KW - 0 KW - Neuroprotective Agents KW - Nitrites KW - Peptide Fragments KW - Receptors, Opioid KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - Dynorphins KW - 74913-18-1 KW - dynorphin (2-17) KW - 83608-80-4 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Nitrites -- metabolism KW - Receptors, Opioid -- drug effects KW - Nerve Degeneration -- chemically induced KW - Nerve Degeneration -- prevention & control KW - Neuroglia -- drug effects KW - Rats KW - Superoxides -- metabolism KW - Rats, Inbred F344 KW - Cells, Cultured KW - Neuroglia -- pathology KW - Peptide Fragments -- pharmacology KW - Lipopolysaccharides -- toxicity KW - Tumor Necrosis Factor-alpha -- metabolism KW - Immunohistochemistry KW - Mesencephalon -- metabolism KW - Mesencephalon -- drug effects KW - Mesencephalon -- pathology KW - Neurons -- drug effects KW - Dopamine -- physiology KW - Dopamine -- metabolism KW - Neuroprotective Agents -- pharmacology KW - Neurons -- pathology KW - Dynorphins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71094960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Femtomolar+concentrations+of+dynorphins+protect+rat+mesencephalic+dopaminergic+neurons+against+inflammatory+damage.&rft.au=Liu%2C+B%3BQin%2C+L%3BYang%2C+S+N%3BWilson%2C+B+C%3BLiu%2C+Y%3BHong%2C+J+S&rft.aulast=Liu&rft.aufirst=B&rft.date=2001-09-01&rft.volume=298&rft.issue=3&rft.spage=1133&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The antimutator phenotype of E. coli mud is only apparent and results from delayed appearance of mutants. AN - 71091985; 11506800 AB - Antimutator strains are strains that have a lower mutation rate than the wild-type strain. We have reexamined the properties of one reported antimutator strain of Escherichia coli, termed mud [Mol. Gen. Genet. 153 (1977) 87]. This strain contains a temperature-sensitive mutation in the purB gene, leading to adenine-dependent growth at higher temperature. When grown at permissive or semi-permissive temperature in the absence of adenine it displays large reductions in the number of both spontaneous and mutagen-induced mutants (e.g. several hundred-fold for valine-resistant mutants). However, our studies show that strains containing the purB allele generate mutations at the same level as the wild-type strain, and that the apparent antimutator effect is the consequence of the delayed appearance of mutants on the selective plates. This delay likely results from the combined stress exerted by the adenine deficiency and the presence of the selective agent (i.e. valine). JF - Mutation research AU - Schaaper, R M AU - Dunn, R L AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA. schaaper@niehs.nih.gov Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 71 EP - 75 VL - 480-481 SN - 0027-5107, 0027-5107 KW - DNA, Bacterial KW - 0 KW - Adenylosuccinate Lyase KW - EC 4.3.2.2 KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Phenotype KW - Alleles KW - Gene Frequency KW - Adenylosuccinate Lyase -- genetics KW - DNA, Bacterial -- genetics KW - DNA Mutational Analysis KW - Temperature KW - Valine -- pharmacology KW - Time Factors KW - Escherichia coli -- drug effects KW - Mutation -- genetics KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71091985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=Recruitment+of+HU+by+piggyback%3A+a+special+role+of+GalR+in+repressosome+assembly.&rft.au=Kar%2C+S%3BAdhya%2C+S&rft.aulast=Kar&rft.aufirst=S&rft.date=2001-09-01&rft.volume=15&rft.issue=17&rft.spage=2273&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oncogenic mutants of RON and MET receptor tyrosine kinases cause activation of the beta-catenin pathway. AN - 71052510; 11486025 AB - beta-Catenin is an oncogenic protein involved in regulation of cell-cell adhesion and gene expression. Accumulation of cellular beta-catenin occurs in many types of human cancers. Four mechanisms are known to cause increases in beta-catenin: mutations of beta-catenin, adenomatous polyposis coli, or axin genes and activation of Wnt signaling. We report a new cause of beta-catenin accumulation involving oncogenic mutants of RON and MET receptor tyrosine kinases (RTKs). Cells transfected with oncogenic RON or MET were characterized by beta-catenin tyrosine phosphorylation and accumulation; constitutive activation of a Tcf transcriptional factor; and increased levels of beta-catenin/Tcf target oncogene proteins c-myc and cyclin D1. Interference with the beta-catenin pathway reduced the transforming potential of mutated RON and MET. Activation of beta-catenin by oncogenic RON and MET constitutes a new pathway, which might lead to cell transformation by these and other mutant growth factor RTKs. JF - Molecular and cellular biology AU - Danilkovitch-Miagkova, A AU - Miagkov, A AU - Skeel, A AU - Nakaigawa, N AU - Zbar, B AU - Leonard, E J AD - Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research and Development Center, Fort Detrick, Frederick, MD 21702, USA. danilkovitch@mail.ncifcrf.gov Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 5857 EP - 5868 VL - 21 IS - 17 SN - 0270-7306, 0270-7306 KW - Axin Protein KW - 0 KW - CTNNB1 protein, mouse KW - Cytoskeletal Proteins KW - Proteins KW - Proto-Oncogene Proteins c-myc KW - Receptors, Cell Surface KW - Repressor Proteins KW - TCF Transcription Factors KW - TCF7L2 protein, human KW - Tcf7l2 protein, mouse KW - Trans-Activators KW - Transcription Factor 7-Like 2 Protein KW - Transcription Factors KW - beta Catenin KW - Cyclin D1 KW - 136601-57-5 KW - Tyrosine KW - 42HK56048U KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - RON protein KW - Receptor Protein-Tyrosine Kinases KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Glycogen Synthase Kinase 3 KW - EC 2.7.11.26 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-myc -- genetics KW - Cyclin D1 -- biosynthesis KW - Mice KW - Transcription Factors -- genetics KW - Proteins -- metabolism KW - Transcriptional Activation KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Dogs KW - Tyrosine -- metabolism KW - Cell Line KW - Cell Transformation, Neoplastic KW - Receptors, Cell Surface -- metabolism KW - Proto-Oncogene Proteins c-met -- genetics KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Proto-Oncogene Proteins c-met -- metabolism KW - Receptors, Cell Surface -- genetics KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Cytoskeletal Proteins -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71052510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Oncogenic+mutants+of+RON+and+MET+receptor+tyrosine+kinases+cause+activation+of+the+beta-catenin+pathway.&rft.au=Danilkovitch-Miagkova%2C+A%3BMiagkov%2C+A%3BSkeel%2C+A%3BNakaigawa%2C+N%3BZbar%2C+B%3BLeonard%2C+E+J&rft.aulast=Danilkovitch-Miagkova&rft.aufirst=A&rft.date=2001-09-01&rft.volume=21&rft.issue=17&rft.spage=5857&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1989 May 11;339(6220):155-6 [2541345] Proc Natl Acad Sci U S A. 1989 Jul;86(14):5291-5 [2546151] EMBO J. 1989 Jun;8(6):1711-7 [2788574] FASEB J. 1990 Feb 1;4(2):176-87 [2404819] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):415-9 [1824873] Science. 1991 Feb 15;251(4995):802-4 [1846706] J Cell Biol. 1991 May;113(4):867-79 [1709169] Cancer Cells. 1991 Jun;3(6):227-32 [1832923] Oncogene. 1991 Nov;6(11):1997-2003 [1719465] Cell. 1991 Nov 29;67(5):901-8 [1835669] Cell. 1992 Jun 26;69(7):1073-87 [1617723] J Cell Biol. 1992 Aug;118(3):703-14 [1639852] Biochem J. 1992 Sep 1;286 ( Pt 2):441-9 [1530576] J Cell Biol. 1992 Nov;119(3):629-41 [1383237] Oncogene. 1992 Dec;7(12):2439-45 [1334250] Oncogene. 1992 Dec;7(12):2549-53 [1334253] Eur J Cancer Prev. 1992 Oct;1 Suppl 3:45-9 [1467788] J Cell Biol. 1993 Feb;120(3):757-66 [8425900] EMBO J. 1993 Jan;12(1):307-14 [8381351] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937-41 [7680481] Oncogene. 1993 May;8(5):1195-202 [8386824] EMBO J. 1993 Jun;12(6):2257-64 [7685273] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6140-4 [8392188] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7696-700 [8356071] EMBO J. 1994 May 1;13(9):2124-30 [8187765] EMBO J. 1994 Aug 1;13(15):3524-32 [8062829] Bioessays. 1994 Jun;16(6):395-404 [8080429] Cell Adhes Commun. 1994 Jan;1(4):295-305 [8081883] Science. 1994 Oct 7;266(5182):117-9 [7939629] J Cell Biol. 1994 Dec;127(5):1375-80 [7962096] J Cell Biol. 1994 Dec;127(6 Pt 1):1743-54 [7528222] Science. 1995 Jan 20;267(5196):381-3 [7824936] Nature. 1995 Feb 23;373(6516):699-702 [7854452] Oncogene. 1995 Feb 16;10(4):739-49 [7862451] Biochem Biophys Res Commun. 1995 Mar 28;208(3):1067-72 [7702605] Blood. 1995 Jun 1;85(11):3093-100 [7538816] Blood. 1995 Nov 1;86(9):3394-403 [7579443] Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10560-4 [7479840] J Immunol. 1996 Apr 15;156(8):2933-40 [8609414] Blood. 1996 May 1;87(9):3704-10 [8611695] J Biol Chem. 1996 Mar 8;271(10):5850-8 [8621456] Biochim Biophys Acta. 1996 Jun 7;1287(2-3):121-49 [8672527] Exp Cell Res. 1996 Jul 10;226(1):39-46 [8660937] Cell. 1996 Sep 6;86(5):787-98 [8797825] Annu Rev Biochem. 1996;65:801-47 [8811196] J Cell Biol. 1997 Jun 2;137(5):1057-68 [9166406] EMBO J. 1997 May 15;16(10):2634-45 [9184210] EMBO J. 1997 Jul 1;16(13):3797-804 [9233789] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11445-50 [9326629] Bioessays. 1997 Oct;19(10):883-91 [9363682] Curr Opin Oncol. 1998 Jan;10(1):81-7 [9466489] EMBO J. 1998 Mar 2;17(5):1371-84 [9482734] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14 [9482916] Science. 1998 Apr 24;280(5363):596-9 [9554852] Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379-83 [2819873] Mol Cell Biol. 1998 May;18(5):2474-85 [9566868] Biochem Biophys Res Commun. 1998 Jun 29;247(3):851-8 [9647782] Oncogene. 1998 Jun 4;16(22):2927-33 [9671413] Oncogene. 1998 Aug 13;17(6):741-9 [9715276] Science. 1998 Sep 4;281(5382):1509-12 [9727977] Clin Cancer Res. 1995 Feb;1(2):147-54 [9815967] Curr Opin Cell Biol. 1998 Oct;10(5):629-39 [9818174] Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14379-83 [9826708] Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14417-22 [9826715] Hybridoma. 1998 Dec;17(6):541-51 [9890710] J Biol Chem. 1999 Mar 5;274(10):6553-8 [10037749] Curr Opin Genet Dev. 1999 Feb;9(1):15-21 [10072352] J Leukoc Biol. 1999 Mar;65(3):345-8 [10080538] Nat Genet. 1999 Apr;21(4):410-3 [10192393] J Biol Chem. 1999 Apr 16;274(16):10681-4 [10196136] J Biol Chem. 1999 Apr 9;274(15):10173-83 [10187801] Nature. 1999 Apr 1;398(6726):422-6 [10201372] Anticancer Res. 1999 Jan-Feb;19(1A):509-17 [10226590] Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-7 [10318916] Oncogene. 1999 Apr 8;18(14):2343-50 [10327054] J Biol Chem. 1999 Jun 4;274(23):16641-5 [10347231] Genes Dev. 1999 Jul 15;13(14):1768-73 [10421629] Biochem Biophys Res Commun. 1999 Aug 2;261(2):406-11 [10425198] J Cell Sci. 1999 Sep;112 Pt 18:3005-14 [10462517] FEBS Lett. 1999 Sep 17;458(2):247-51 [10481074] Nat Genet. 1999 Oct;23(2):159-65 [10508511] Curr Opin Genet Dev. 1999 Oct;9(5):595-603 [10508699] J Cell Physiol. 1999 Dec;181(3):507-14 [10528237] Cytokine Growth Factor Rev. 1999 Sep-Dec;10(3-4):255-65 [10647780] Biochem Biophys Res Commun. 2000 Feb 16;268(2):243-8 [10679188] Mol Cell Biol. 2000 Mar;20(6):2218-27 [10688668] Oncogene. 2000 Jan 27;19(4):537-45 [10698523] Nat Genet. 2000 Mar;24(3):206-8 [10700164] Nat Genet. 2000 Mar;24(3):245-50 [10700176] Oncogene. 2000 Feb 21;19(8):1065-71 [10713691] Science. 2000 Mar 3;287(5458):1606-9 [10733430] Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4262-6 [10759547] J Biol Chem. 2000 May 19;275(20):14783-6 [10747844] Oncogene. 2000 Jun 22;19(27):3041-9 [10871856] Oncogene. 2000 Jun 15;19(26):2996-3002 [10871851] Biochem Biophys Res Commun. 1982 Aug;107(3):1104-9 [6291515] J Mol Med (Berl). 1996 Sep;74(9):505-13 [8892055] Cell. 1996 Nov 1;87(3):531-42 [8898205] EMBO J. 1996 Nov 1;15(21):5866-75 [8918464] J Biol Chem. 1996 Dec 6;271(49):31049-54 [8940099] Mol Cell Biol. 1996 Dec;16(12):7072-83 [8943362] Oncogene. 1996 Nov 21;13(10):2167-75 [8950984] Neuron. 1996 Dec;17(6):1157-72 [8982163] J Biol Chem. 1997 Feb 14;272(7):4536-43 [9020180] Science. 1997 Mar 21;275(5307):1784-7 [9065401] Science. 1997 Mar 21;275(5307):1787-90 [9065402] Science. 1997 Mar 21;275(5307):1790-2 [9065403] Pathol Int. 1996 Dec;46(12):933-8 [9110344] Nat Genet. 1997 May;16(1):68-73 [9140397] Dev Dyn. 1999 Oct;216(2):168-76 [10536056] Bioessays. 1999 Dec;21(12):1021-30 [10580987] J Biol Chem. 1999 Dec 17;274(51):36734-40 [10593980] Am J Pathol. 1999 Dec;155(6):1885-91 [10595919] Oncogene. 1999 Nov 4;18(46):6343-56 [10597234] Nature. 1984 Sep 6-11;311(5981):29-33 [6590967] J Cell Sci. 1985 Aug;77:209-23 [3841349] Proc Natl Acad Sci U S A. 1986 Sep;83(17):6489-93 [3529086] Nature. 1987 May 21-27;327(6119):239-42 [2952888] Biochem Biophys Res Commun. 1987 Aug 31;147(1):259-66 [3632668] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Social-cognitive theory mediators of behavior change in the National Institute of Mental Health Multisite HIV Prevention Trial AN - 57755933; 187998 AB - This trial was an intervention to reduce sexual HIV risk behaviors among 3706 low-income at-risk men and women at seven US research sites. The intervention, based on social-cognitive theory and designed to influence behavior change by improving expected outcomes of condom use and increasing knowledge, skills, and self-efficacy to execute safer sex behaviors, was effective relative to a control condition in reducing sexual risk behavior. At 3 months after completion of the intervention, measures of these potential mediators were higher in the intervention than in the control condition. Although the effect of the intervention on sexual risk behavior was significantly reduced when the variables were controlled statistically, supporting the hypothesis of their mediation in the intervention effect, most of the effect remained unexplained, indicating the influence of unmeasured factors on outcome. (Original abstract - amended) JF - Health Psychology AU - National Institute of Mental Health Multisite HIV Prevention Trial Group AD - National Institute of Mental Health Multisite HIV Prevention Trial Group Y1 - 2001/09// PY - 2001 DA - September 2001 SP - 369 EP - 376 VL - 20 IS - 5 SN - 0278-6133, 0278-6133 KW - Condoms KW - Social cognitive theory KW - Human immunodeficiency virus KW - Sexual practices KW - Health promotion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57755933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Psychology&rft.atitle=Social-cognitive+theory+mediators+of+behavior+change+in+the+National+Institute+of+Mental+Health+Multisite+HIV+Prevention+Trial&rft.au=National+Institute+of+Mental+Health+Multisite+HIV+Prevention+Trial+Group&rft.aulast=National+Institute+of+Mental+Health+Multisite+HIV+Prevention+Trial+Group&rft.aufirst=&rft.date=2001-09-01&rft.volume=20&rft.issue=5&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Health+Psychology&rft.issn=02786133&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2002-02-11 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Sexual practices; Health promotion; Condoms; Social cognitive theory ER - TY - JOUR T1 - Child care and children's peer interaction at 24 and 36 months: the NICHD study of early child care AN - 38313150; 2294048 JF - Child development Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 1478 EP - 1500 VL - 72 IS - 5 SN - 0009-3920, 0009-3920 KW - Sociology KW - Case studies KW - Mothers KW - Peer groups KW - Social interaction KW - Child care KW - Child development KW - Family studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/38313150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+development&rft.atitle=Child+care+and+children%27s+peer+interaction+at+24+and+36+months%3A+the+NICHD+study+of+early+child+care&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2001-09-01&rft.volume=20&rft.issue=5&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Health+Psychology&rft.issn=02786133&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - SuppNotes - Data from the National Institute of Child Health and Human Development Study of Early Child Care were examined to determine how children's experiences in child care were related to peer competence at 24 and 36 months of age, after controlling for the effects of family and child characteristics. Peer competence was assessed using mother and caregiver ratings as well as observations of children with their peers in child care, and at 36 months from observations of dyadic play with a familiar peer. Consistent, albeit modest, relations were found between child-care experiences in the first 3 years of life and children's peer competencies. Positive, responsive caregiver behavior was the feature of child care most consistently associated with positive, skilled peer interaction in child care. Children with more experience in child-care settings with other children present were observed to be more positive and skilled in their peer play in child care, although their caregivers rated them as more negative with playmates. Children who spent more hours in child care were rated by their caregivers as more negative in peer play, but their observed peer play was not related to the quantity of care. Child-care experiences were not associated with peer competence as rated by mothers or as observed in dyadic play with a friend. Maternal sensitivity and children's cognitive and language competence predicted peer competence across all settings and informants, suggesting that family and child-care contexts may play different, but complementary roles in the development of early emerging individual differences in peer interaction. N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 2197 2212 6075 3483; 4783; 2192; 9347; 11860 11907; 2056 10902; 8317 9184 ER - TY - JOUR T1 - The impact of genomics on the biotechnology industry AN - 20322960; 8934334 JF - Expert Opinion in Biological Therapy AU - E, Wang AU - M C, Panelli AU - F M, Marincola AD - Immunogenetics Laboratory of the Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda MD, USA, marincola@nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 749 EP - 751 PB - Ashley Publications Ltd., Unitec House, 3rd Floor 2 Albert Place, Finchley Central London, N3 1QB UK, [URL:http://ernesto.ashley-pub.com/] VL - 1 IS - 5 SN - 1471-2598, 1471-2598 KW - Biotechnology and Bioengineering Abstracts KW - genomics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20322960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Opinion+in+Biological+Therapy&rft.atitle=The+impact+of+genomics+on+the+biotechnology+industry&rft.au=E%2C+Wang%3BM+C%2C+Panelli%3BF+M%2C+Marincola&rft.aulast=E&rft.aufirst=Wang&rft.date=2001-09-01&rft.volume=1&rft.issue=5&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=Expert+Opinion+in+Biological+Therapy&rft.issn=14712598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - genomics ER - TY - JOUR T1 - GeneMachine: gene prediction and sequence annotation AN - 18348400; 5290073 AB - A number of free-standing programs have been developed in order to help researchers find potential coding regions and deduce gene structure for long stretches of what is essentially 'anonymous DNA'. As these programs apply inherently different criteria to the question of what is and is not a coding region, multiple algorithms should be used in the course of positional cloning and positional candidate projects to assure that all potential coding regions within a previously-identified critical region are identified. We have developed a gene identification tool called GeneMachine which allows users to query multiple exon and gene prediction programs in an automated fashion. BLAST searches are also performed in order to see whether a previously-characterized coding region corresponds to a region in the query sequence. A suite of Perl programs and modules are used to run MZEF, GENSCAN, GRAIL 2, FGENES, RepeatMasker, Sputnik, and BLAST. The results of these runs are then parsed and written into ASN.1 format. Output files can be opened using NCBI Sequin, in essence using Sequin as both a workbench and as a graphical viewer. The main feature of GeneMachine is that the process is fully automated; the user is only required to launch GeneMachine and then open the resulting file with Sequin. Annotations can then be made to these results prior to submission to GenBank, thereby increasing the intrinsic value of these data. GeneMachine is freely-available for download at http://genome.nhgri.nih.gov/genemachine. A public Web interface to the GeneMachine server for academic and not-for-profit users is available at http://genemachine.nhgri.nih.gov. The Web supplement to this paper may be found at http://genome.nhgri.nih.gov/genemachine/supplement/. JF - Bioinformatics AU - Makalowska, I AU - Ryan, J F AU - Baxevanis, AD AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A-22, Bethesda, MD 20892, USA, andy@nhgri.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 843 EP - 844 VL - 17 IS - 9 SN - 1367-4803, 1367-4803 KW - predictions KW - DNA sequencing KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Computer programs KW - Bioinformatics KW - Computer applications KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18348400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=GeneMachine%3A+gene+prediction+and+sequence+annotation&rft.au=Makalowska%2C+I%3BRyan%2C+J+F%3BBaxevanis%2C+AD&rft.aulast=Makalowska&rft.aufirst=I&rft.date=2001-09-01&rft.volume=17&rft.issue=9&rft.spage=843&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Computer programs; Computer applications ER - TY - JOUR T1 - Body Mass Index as a Measure of Adiposity in Children and Adolescents: Relationship to Adiposity by Dual Energy X-Ray Absorptiometry and to Cardiovascular Risk Factors AN - 18333969; 5384430 AB - Body mass index is widely used as a measure of adiposity in adults, but its use in children and adolescents is controversial. We assessed body mass index as a measure of adiposity in children and adolescents between the ages of 5 and 20 yr examined as part of the NIH survey of health in the Pima Indian population. Body mass index (measured in 985 subjects and analyzed in 3 age groups: 5-9, 10-14, and 15-19 yr, in both sexes) was compared cross-sectionally to percent fat and fat mass derived from dual energy x-ray absorptiometry and to fasting and 2-h plasma glucose, systolic and diastolic blood pressures, cholesterol, high density lipoprotein cholesterol, fasting insulin, and triglycerides. Body mass index was strongly correlated in all age groups to both percent fat (r = 0.83-0.94; for each group, P < 0.0001) and fat mass (r = 0.96-0.98; P < 0.0001). The relationship of body mass index to percent fat was different in males and females; differences were more marked in older age groups. Body mass index, percent fat, and fat mass showed similar degrees of correlation to metabolic measures in childhood. Body mass index is strongly associated with measures of adiposity derived from dual energy x-ray absorptiometry. Both measures show similar associations with cardiovascular risk factors in Pima Indian children. JF - Journal of Clinical Endocrinology and Metabolism AU - Lindsay, R S AU - Hanson, R L AU - Roumain, J AU - Ravussin, E AU - Knowler, W C AU - Tataranni, P A AD - 1550 East Indian School Road, Phoenix, Arizona 85014, USA, rlindsay@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 4061 EP - 4067 VL - 86 IS - 9 SN - 0021-972X, 0021-972X KW - Physical Education Index KW - Risk factors KW - Adolescence KW - Children KW - Body composition KW - Heart diseases KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18333969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.atitle=Body+Mass+Index+as+a+Measure+of+Adiposity+in+Children+and+Adolescents%3A+Relationship+to+Adiposity+by+Dual+Energy+X-Ray+Absorptiometry+and+to+Cardiovascular+Risk+Factors&rft.au=Lindsay%2C+R+S%3BHanson%2C+R+L%3BRoumain%2C+J%3BRavussin%2C+E%3BKnowler%2C+W+C%3BTataranni%2C+P+A&rft.aulast=Lindsay&rft.aufirst=R&rft.date=2001-09-01&rft.volume=86&rft.issue=9&rft.spage=4061&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Body composition; Children; Adolescence; Risk factors; Heart diseases ER - TY - JOUR T1 - Dietary N-acetyl-L-cysteine modulates benzo[a]pyrene-induced skin tumors in cancer-prone p53 haploinsufficient Tg.AC ( upsilon -Ha-ras) mice AN - 18293195; 5338059 AB - Epidemiologic studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence from clinical trials and laboratory data suggest that in some cases individual antioxidant supplements may actually exacerbate carcinogenesis. Our goal was to explore these paradoxical activities in a rodent model that possesses genotypic characteristics of human cancers. We selected the p53 haploinsufficient Tg.AC ( upsilon -Ha-ras) mouse as a model, because it contains an activated, carcinogeninducible ras oncogene and an inactivated p53 tumor suppressor gene, which are frequent genetic alterations in human cancers. These mice develop chemically induced benign and malignant skin tumors rapidly which can easily be quantified. Mice were fed basal diets with or without 3% N-acetyl-L-cysteine (NAC), a well-recognized antioxidant, prior to, during and after topical application of the carcinogen benzo[a]pyrene (64 mu g/mouse) applied twice per week for 7 weeks. Tumor incidence exceeded 90% for both groups, and NAC did not reduce tumor latency. Mice fed NAC displayed a 43% reduction (P < 0.05) in tumor multiplicity and delayed the appearance of lesions (P < 0.05). Dietary NAC also significantly (P < 0.05) improved group survival by 5 weeks. Total tumor yields were reduced in both dietary groups but malignant spindle cell tumors (SCT) increased by 25% in NAC-fed mice. The upsilon -Ha-ras oncogene and p53 protein products were clearly co-expressed in both benign and malignant lesions from both dietary groups. In summary, dietary supplementation with NAC was chemopreventive, but the marginal increase in SCT suggests a paradoxical effect. JF - Carcinogenesis AU - Martin, K R AU - Trempus, C AU - Saulnier, M AU - Kari, F W AU - Barrett, J C AU - French, JE AD - Transgenic Carcinogenesis Unit, Laboratory of Environmental Carcinogenesis and Mutagenesis and Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 1373 EP - 1378 VL - 22 IS - 9 SN - 0143-3334, 0143-3334 KW - mice KW - inactivation KW - N-Acetyl-L-cysteine KW - N-Acetylcysteine KW - chemopreventive agents KW - Oncogenes & Growth Factors Abstracts; Toxicology Abstracts KW - Ras protein KW - Skin KW - Tumorigenesis KW - Benzo(a)pyrene KW - p53 protein KW - X 24190:Polycyclic hydrocarbons KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18293195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Dietary+N-acetyl-L-cysteine+modulates+benzo%5Ba%5Dpyrene-induced+skin+tumors+in+cancer-prone+p53+haploinsufficient+Tg.AC+%28+upsilon+-Ha-ras%29+mice&rft.au=Martin%2C+K+R%3BTrempus%2C+C%3BSaulnier%2C+M%3BKari%2C+F+W%3BBarrett%2C+J+C%3BFrench%2C+JE&rft.aulast=Martin&rft.aufirst=K&rft.date=2001-09-01&rft.volume=22&rft.issue=9&rft.spage=1373&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ras protein; Benzo(a)pyrene; Skin; Tumorigenesis; p53 protein ER - TY - JOUR T1 - Endothelial cell-based systemic gene therapy of metastatic melanoma AN - 18270088; 5324127 AB - Cancer metastasis accounts for a significant proportion of morbidity and mortality in patients. Effective means of treating disseminated disease remains elusive. The purpose of this study was to determine whether genetically modified endothelial cells (GMEC) can selectively target and deliver recombinant therapeutic molecules to sites of tumor metastases. Following the establishment of lung metastases of 4T1 mammary tumor in mice, intravenously (i.v.) administered, lacZ transgene-expressing endothelial cells (lacZ-GMEC) accumulated at the tumor sites. An average of 32% and 90% of the pulmonary metastases were X-gal stained following one and three tail vein injections of 10 super(5) lacZ-GMEC, respectively. The linear pattern of X-gal staining seen within the tumor sites and the histological appearance of the tumor vasculature were consistent with the incorporation of lacZ-GMEC into blood vessels. In C57Bl/6 mice harboring lung metastases of melanoma, the administration of three sequential i.v. injections of 10 super(5) endothelial cells expressing a human interleukin 2 transgene abrogated the tumor metastases and prolonged survival of the animals. These results demonstrate that i.v.-administered GMEC can selectively accumulate, survive, and stably express exogenous genes at multiple tumor sites. These findings support a role for i.v.-administered GMEC as a potential therapeutic strategy for the systemic treatment of cancer metastases. JF - Cancer Gene Therapy AU - Ojeifo, JO AU - Lee, H R AU - Rezza, P AU - Su, N AU - Zwiebel, JA AD - EPN 7114, 6130 Executive Boulevard, Rockville, MD 20852, USA, jz43j@nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 636 EP - 648 VL - 8 IS - 9 SN - 0929-1903, 0929-1903 KW - C57Bl/6 mice KW - lacZ gene KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Metastases KW - Gene therapy KW - Mammary gland KW - Endothelium KW - Melanoma KW - G 07397:Rodentia (mice) KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33182:Packaging cell lines for gene therapy vectors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18270088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Endothelial+cell-based+systemic+gene+therapy+of+metastatic+melanoma&rft.au=Ojeifo%2C+JO%3BLee%2C+H+R%3BRezza%2C+P%3BSu%2C+N%3BZwiebel%2C+JA&rft.aulast=Ojeifo&rft.aufirst=JO&rft.date=2001-09-01&rft.volume=8&rft.issue=9&rft.spage=636&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Endothelium; Melanoma; Metastases; Mammary gland ER - TY - JOUR T1 - Patterns of Resistance to Exonuclease Digestion of Oligonucleotides Containing Polycyclic Aromatic Hydrocarbon Diol Epoxide Adducts at N super(6) of Deoxyadenosine AN - 18236296; 5298856 AB - The effect of adduct stereochemistry on the susceptibility to hydrolysis by snake venom (VPD) and bovine spleen (SPD) phosphodiesterases was investigated with short deoxyoligonucleotides containing defined adducts derived from alkylation of the exocyclic 6-amino group of dA by polycyclic aromatic hydrocarbon diol epoxides (DEs). In accordance with several earlier reports, we have found that adducts with R configuration at the site of attachment of dA to the DE moiety derived from either benzo[a]pyrene (BaP) or benzo[c] phenanthrene (BcPh) are generally more resistant to hydrolysis by VPD than are their (S)-diastereomers. The reaction with VPD initially yields a fragment containing the adducted dA residue at its 3'-end, which slowly hydrolyzes to a dimer (pXpA*) with an intact 5'-phosphodiester bond to the adducted dA. With several of the adducts studied, this dimer underwent cleavage to release eventually the monomeric adduct p(dA*). Adducts derived from cis opening of the epoxide ring of both BaP and BcPh DEs were considerably more resistant to VPD than the corresponding trans-opened adducts. Although several previous investigations had suggested that oligonucleotides containing adducts which have S configuration at the site of attachment of the hydrocarbon to adenine are more resistant to cleavage by SPD than are their (R)-diastereomers, the present results with a more extensive set of oligonucleotides indicate that SPD, in contrast to VPD, exhibits little discrimination between adducts with R and S configuration at the site of attachment to the base. Notably, for both enzymes, the most resistant internucleotide linkage (the bond 3'-sugar to phosphate for VPD and 5'-sugar to phosphate for SPD) is between the modified base and the base immediately 5' to it, regardless of the configuration of the adduct. JF - Chemical Research in Toxicology AU - Ilankumaran, P AU - Pannell, L K AU - Gebreselassie, P AU - Pilcher, A S AU - Yagi, H AU - Sayer, J M AU - Jerina, D M AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, Maryland 20892-0820, USA Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 1330 EP - 1338 VL - 14 IS - 9 SN - 0893-228X, 0893-228X KW - diol epoxides KW - exonuclease KW - Toxicology Abstracts KW - Polycyclic aromatic hydrocarbons KW - Adducts KW - Venom KW - Hydrolysis KW - Stereochemistry KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18236296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Patterns+of+Resistance+to+Exonuclease+Digestion+of+Oligonucleotides+Containing+Polycyclic+Aromatic+Hydrocarbon+Diol+Epoxide+Adducts+at+N+super%286%29+of+Deoxyadenosine&rft.au=Ilankumaran%2C+P%3BPannell%2C+L+K%3BGebreselassie%2C+P%3BPilcher%2C+A+S%3BYagi%2C+H%3BSayer%2C+J+M%3BJerina%2C+D+M&rft.aulast=Ilankumaran&rft.aufirst=P&rft.date=2001-09-01&rft.volume=14&rft.issue=9&rft.spage=1330&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Polycyclic aromatic hydrocarbons; Adducts; Stereochemistry; Hydrolysis; Venom ER - TY - JOUR T1 - Immunohistochemical Detection of Protein Adducts of 2,4-Dinitrochlorobenzene in Antigen Presenting Cells and Lymphocytes after Oral Administration to Mice: Lack of a Role of Kupffer Cells in Oral Tolerance AN - 18236254; 5298841 AB - Although current studies suggest that most drug-induced allergic reactions (DIARS) are caused by immunogenic conjugates formed from the reaction of a reactive metabolite of a drug with cellular proteins, it is not clear why these reactions are relatively rare. One possible pathway that may explain the low incidence of DIARS in many cases is oral tolerance, an antigen-specific immunological hyporesponsiveness induced by oral administration of antigens. The mechanism of oral tolerance, however, is not clearly understood and is difficult to study directly with drugs, because animal models of DIARS have been elusive. We chose 2,4-dinitrochlorobenzene (DNCB) as a model compound to circumvent this problem because animal models of allergic reactions have been established for this compound. DNCB forms immunogenic 2,4-dinitrophenylated (DNP) protein conjugates that can induce immune reactions and it causes oral tolerance when it is fed to animals prior to sensitization. We hypothesized that DNP-protein conjugates may have a role in oral tolerance. To test this idea, we have begun to identify cells bearing these conjugates after the oral administration of DNCB. Female C57BL/6J mice were fed DNCB and tissues were examined after 6 and 24 h. Immunohistochemical analysis indicated the presence of DNP-protein conjugates in enterocytes of the small intestine, in macrophages and lymphocytes of the mesenteric lymph nodes, in dendritic cells and lymphocytes of the spleen, and in Kupffer cells and other sinusoidal cells of the liver. It was found that Kupffer cell depletion did not affect oral tolerance to DNCB. The findings suggest that the cells bearing DNP-protein conjugates, other than Kupffer cells, in the liver and other tissues may be important in the induction of oral tolerance against DNCB. Protein adducts of drugs administered orally may also be present in these cells, and they may have a role in the downregulation of DIARS in many individuals. JF - Chemical Research in Toxicology AU - Ju, C AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 1209 EP - 1217 VL - 14 IS - 9 SN - 0893-228X, 0893-228X KW - 2,4-Dinitrochlorobenzene KW - mice KW - Toxicology Abstracts KW - Kupffer cells KW - Hypersensitivity KW - Adducts KW - 1-Chloro-2,4-dinitrobenzene KW - Animal models KW - Pharmaceuticals KW - Immunohistochemistry KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18236254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Immunohistochemical+Detection+of+Protein+Adducts+of+2%2C4-Dinitrochlorobenzene+in+Antigen+Presenting+Cells+and+Lymphocytes+after+Oral+Administration+to+Mice%3A+Lack+of+a+Role+of+Kupffer+Cells+in+Oral+Tolerance&rft.au=Ju%2C+C%3BPohl%2C+L+R&rft.aulast=Ju&rft.aufirst=C&rft.date=2001-09-01&rft.volume=14&rft.issue=9&rft.spage=1209&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Immunohistochemistry; 1-Chloro-2,4-dinitrobenzene; Adducts; Kupffer cells; Hypersensitivity; Pharmaceuticals; Animal models ER - TY - JOUR T1 - Parkinsonism and occupational exposure to pesticides AN - 18235994; 5300260 AB - To examine the risk of parkinsonism related to lifetime occupational exposure to pesticides among a cohort of men, mostly orchardists, in Washington State. All 310 subjects in this study had previously participated in a cohort study of men occupationally exposed to pesticides. Subjects were given a structured neurological examination and completed a self administered questionnaire which elicited detailed information on pesticide (insecticide, herbicide, and fungicide) use throughout their working careers. Demographic characteristics were also sought. Subjects had a mean age of 69.6 years (range 49-96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was defined by the presence of two or more of rest tremor, rigidity, bradykinesia, and impairment of postural reflexes in subjects not on antiparkinsonian medication, or the presence of at least one sign if they were on such medication. Parkinson's disease was not studied explicitly because of the difficulty in distinguishing it from other parkinsonian syndromes. A generalised linear model was used to estimate prevalence ratios (PRs) for parkinsonism relative to history of farming, pesticide use, and use of well water. A PR of 2.0 (95% confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest tertile of years of exposure to pesticides; a similarly increased, non-significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)), although a trend test did not show a significant exposure-response relation. No increased risks were found associated with specific pesticides or pesticide classes, nor with a history of farming or use of well water. Parkinsonism may be associated with long term occupational exposure to pesticides, although no associations with specific pesticides could be detected. This finding is consistent with most of the publications on this topic. JF - Occupational and Environmental Medicine AU - Engel, L S AU - Checkoway, H AU - Keifer, M C AU - Seixas, N S AU - Longstreth, WT Jr AU - Scott, K C AU - Hudnell, K AU - Anger, W K AU - Camicioli, R AD - Occupational Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, EPS 8113, MSC 7240, Bethesda, MD 20892-7240, USA, engell@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 582 EP - 589 VL - 58 IS - 9 SN - 1351-0711, 1351-0711 KW - man KW - Parkinson's disease KW - nervous system diseases KW - orchards KW - Toxicology Abstracts; Health & Safety Science Abstracts; Risk Abstracts KW - Farms KW - Orchards KW - USA, Washington KW - Pesticides KW - Nervous system diseases KW - Occupational exposure KW - R2 23080:Industrial and labor KW - X 24132:Chronic exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18235994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Parkinsonism+and+occupational+exposure+to+pesticides&rft.au=Engel%2C+L+S%3BCheckoway%2C+H%3BKeifer%2C+M+C%3BSeixas%2C+N+S%3BLongstreth%2C+WT+Jr%3BScott%2C+K+C%3BHudnell%2C+K%3BAnger%2C+W+K%3BCamicioli%2C+R&rft.aulast=Engel&rft.aufirst=L&rft.date=2001-09-01&rft.volume=58&rft.issue=9&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, Washington; Occupational exposure; Pesticides; Farms; Nervous system diseases; Parkinson's disease; Orchards ER - TY - JOUR T1 - Isolation and Characterization of a Mutant Chinese Hamster Ovary Cell Line That Is Resistant to Chlamydia trachomatis Infection at a Novel Step in the Attachment Process AN - 18177891; 5157382 AB - Host factors involved in Chlamydia trachomatis pathogenesis were investigated by random chemical mutagenesis of Chinese hamster ovary (CHO-K1) cells followed by selection for clones resistant to chlamydial infection. A clonal mutant cell line, D4.1-3, refractory to infection by the C. trachomatis L2 serovar was isolated. The D4.1-3 cell line appears to be lacking in a previously undescribed temperature-dependent and heparin-resistant binding step that occurs subsequent to engagement of cell surface heparan sulfate by L2 elementary bodies. This novel binding step differentiates the lymphogranuloma venereum (LGV) serovar from other serovars and may contribute the different pathologies associated with LGV and non-LGV strains. JF - Infection and Immunity AU - Carabeo, R A AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories., Ted_Hackstadt@NIH.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 5899 EP - 5904 VL - 69 IS - 9 SN - 0019-9567, 0019-9567 KW - CHO-K1 cells KW - Microbiology Abstracts B: Bacteriology KW - Attachment KW - Chlamydia trachomatis KW - Disease resistance KW - Pathogenesis KW - Mutagenesis KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18177891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Isolation+and+Characterization+of+a+Mutant+Chinese+Hamster+Ovary+Cell+Line+That+Is+Resistant+to+Chlamydia+trachomatis+Infection+at+a+Novel+Step+in+the+Attachment+Process&rft.au=Carabeo%2C+R+A%3BHackstadt%2C+T&rft.aulast=Carabeo&rft.aufirst=R&rft.date=2001-09-01&rft.volume=69&rft.issue=9&rft.spage=5899&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.9.5899-5904.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Disease resistance; Pathogenesis; Mutagenesis; Attachment DO - http://dx.doi.org/10.1128/IAI.69.9.5899-5904.2001 ER - TY - JOUR T1 - Mutualism versus Independence: Strategies of Mixed-Species Oral Biofilms In Vitro Using Saliva as the Sole Nutrient Source AN - 18176671; 5157393 AB - During initial dental plaque formation, the ability of a species to grow when others cannot would be advantageous, and enhanced growth through interspecies and intergeneric cooperation could be critical. These characteristics were investigated in three coaggregating early colonizers of the tooth surface (Streptococcus gordonii DL1, Streptococcus oralis 34, and Actinomyces naeslundii T14V). Area coverage and cell cluster size measurements showed that attachment of A. naeslundii and of S. gordonii to glass flowcells was enhanced by a salivary conditioning film, whereas attachment of S. oralis was hindered. Growth experiments using saliva as the sole carbon and nitrogen source showed that A. naeslundii was unable to grow either in planktonic culture or as a biofilm, whereas S. gordonii grew under both conditions. S. oralis grew planktonically, but to a much lower maximum cell density than did S. gordonii; S. oralis did not grow reproducibly as a biofilm. Thus, only S. gordonii possessed all traits advantageous for growth as a solitary and independent resident of the tooth. Two-species biofilm experiments analyzed by laser confocal microscopy showed that neither S. oralis nor A. naeslundii grew when coaggregated pairwise with S. gordonii. However, both S. oralis and A. naeslundii showed luxuriant, interdigitated growth when paired together in coaggregated microcolonies. Thus, the S. oralis-A. naeslundii pair formed a mutualistic relationship, potentially contact dependent, that allows each to grow where neither could survive alone. S. gordonii, in contrast, neither was hindered by nor benefited from the presence of either of the other strains. The formation of mutually beneficial interactions within the developing biofilm may be essential for certain initial colonizers to be retained during early plaque development, whereas other initial colonizers may be unaffected by neighboring cells on the substratum. JF - Infection and Immunity AU - Palmer Jr, RJ AU - Kazmerzak, K AU - Hansen, M C AU - Kolenbrander, P E AD - National Institutes of Health/NIDCR, Bldg. 30, Room 310, 30 Convent Dr. MSC 4350, Bethesda, MD 20892-4350., pkolenbrander@dir.nidcr.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 5794 EP - 5804 VL - 69 IS - 9 SN - 0019-9567, 0019-9567 KW - mixed species KW - Microbiology Abstracts B: Bacteriology KW - Teeth KW - Nutrients KW - Dental plaque KW - Actinomyces naeslundii KW - Colonization KW - Streptococcus gordonii KW - Oral microflora KW - Mutualism KW - Saliva KW - Biofilms KW - Plankton KW - Streptococcus oralis KW - J 02844:Dental and oral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18176671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Mutualism+versus+Independence%3A+Strategies+of+Mixed-Species+Oral+Biofilms+In+Vitro+Using+Saliva+as+the+Sole+Nutrient+Source&rft.au=Palmer+Jr%2C+RJ%3BKazmerzak%2C+K%3BHansen%2C+M+C%3BKolenbrander%2C+P+E&rft.aulast=Palmer+Jr&rft.aufirst=RJ&rft.date=2001-09-01&rft.volume=69&rft.issue=9&rft.spage=5794&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.9.5794-5804.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus oralis; Streptococcus gordonii; Actinomyces naeslundii; Plankton; Teeth; Colonization; Dental plaque; Oral microflora; Biofilms; Saliva; Nutrients; Mutualism DO - http://dx.doi.org/10.1128/IAI.69.9.5794-5804.2001 ER - TY - JOUR T1 - Cocaine affects the dynamics of cytoskeletal proteins via sigma receptors AN - 18122573; 5216580 AB - Cytoskeletal proteins are important in protein trafficking, membrane protein clustering, dendrite growth and the morphological maintenance of neurons. Sigma sub(1) receptors are unique endoplasmic reticular (ER) proteins that bind (+)benzomorphans, neurosteroids and psychotropic drugs such as cocaine. Cocaine, via sigma sub(1) receptors, can cause the dissociation of a cytoskeletal adaptor protein ankyrin from inositol (1,4,5)-trisphosphate [Ins(1,4,5)P sub(3)] receptors on the ER as a sigma sub(1)-receptor-ankyrin complex, which then translocates to the plasma membrane and nucleus. The dissociation of sigma sub(1)-receptor-ankyrin from Ins(1,4,5)P sub(3) receptors also increases the intracellular Ca super(2+) concentration {[Ca super(2+)] sub(i)}, which affects the activity of cytoskeletal proteins. Furthermore, cocaine might increase [Ca super(2+)] sub(i) via phospholipase C (PLC)-linked dopamine D1 receptors. We hypothesize that cocaine might cause life-long changes in neurons via cytoskeletal proteins by interacting with both D1 receptors and sigma sub(1) receptors. JF - Trends in Pharmacological Sciences AU - Su, Tsung-Ping AU - Hayashi, Teruo AD - Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, TSU@intra.nida.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 456 EP - 458 VL - 22 IS - 9 SN - 0165-6147, 0165-6147 KW - sigma receptors KW - Calcium & Calcified Tissue Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - Inositol 1,4,5-trisphosphate receptors KW - Dopamine D1 receptors KW - Calcium (intracellular) KW - Cytoskeleton KW - Reviews KW - Neurons KW - Ankyrin KW - Proteins KW - Sigma receptors KW - Cocaine KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse KW - T 20019:Cellular calcium, channels and currents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18122573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Pharmacological+Sciences&rft.atitle=Cocaine+affects+the+dynamics+of+cytoskeletal+proteins+via+sigma+receptors&rft.au=Su%2C+Tsung-Ping%3BHayashi%2C+Teruo&rft.aulast=Su&rft.aufirst=Tsung-Ping&rft.date=2001-09-01&rft.volume=22&rft.issue=9&rft.spage=456&rft.isbn=&rft.btitle=&rft.title=Trends+in+Pharmacological+Sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cocaine; Cytoskeleton; Sigma receptors; Calcium (intracellular); Dopamine D1 receptors; Inositol 1,4,5-trisphosphate receptors; Ankyrin; Neurons; Reviews; Proteins ER - TY - JOUR T1 - Optochin Resistance in Streptococcus pneumoniae: Mechanism, Significance, and Clinical Implications AN - 18103292; 5185113 AB - Traditionally, Streptococcus pneumoniae is identified in the laboratory by demonstrating susceptibility to optochin. Between 1992 and 1998, 4 pneumococcal isolates exhibiting optochin resistance were recovered from patients at Children's National Medical Center. Three of the 4 isolates consisted of mixed populations of optochin-resistant and -susceptible organisms. Both subpopulations had identical antibiograms, serotypes, and restriction fragment profiles. The other isolate was uniformly resistant to optochin. Resistant strains had MICs of optochin 4-30-fold higher than susceptible strains, belonged to different serotypes, and had dissimilar restriction fragment profiles, indicating clonal unrelatedness. Resistance arose from single point mutations in either the a-subunit (W206S) or the c-subunit (G20S, M23I, and A49T) of H super(+)-ATPase. There is speculation of a possible association between exposure to antimalarial drugs and evolution of optochin resistance. alpha -Hemolytic streptococci resistant to optochin, particularly invasive isolates, should be tested for bile solubility or with an S. pneumoniae DNA probe before identification as viridans streptococci. JF - Journal of Infectious Diseases AU - Pikis, A AU - Campos, J M AU - Rodriguez, W J AU - Keith, J M AD - Vaccine and Therapeutic Development Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 582 EP - 590 VL - 184 IS - 5 SN - 0022-1899, 0022-1899 KW - mechanism KW - optochin KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Streptococcus pneumoniae KW - Reviews KW - Drug resistance KW - Antimalarial agents KW - A 01064:Microbial resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18103292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=Positive+regulation+of+cell-cell+and+cell-substrate+adhesion+by+protein+kinase+A.&rft.au=Whittard%2C+J+D%3BAkiyama%2C+S+K&rft.aulast=Whittard&rft.aufirst=J&rft.date=2001-09-01&rft.volume=114&rft.issue=&rft.spage=3265&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; Antimalarial agents; Drug resistance; Reviews ER - TY - JOUR T1 - The interaction of male and female reproductive strategies and paternity in wild Japanese macaques, Macaca fuscata AN - 18099900; 5200855 AB - Japanese macaques reside in large, mixed-sex social groups in which various reproductive strategies of both sexes operate simultaneously. This report represents the first study combining behavioural and genetic data to examine the interaction of male and female reproductive strategies in primates (N=15 adult males, N=15 adult females, Yakushima Island, Japan). During one mating season, socially dominant males monopolized most female matings. Furthermore, the six offspring sired by troop males were more likely sired by higher-ranking males than lower-ranking males. Nontroop males sired three additional offspring in the troop. Lower-ranking troop males avoided direct competition with higher-ranking males by engaging in sneak copulations with females outside of the presence of other males. Also, females expressed mate choice behaviour towards multiple males of various dominance ranks. Thus, the female strategy of attempting to mate with multiple males conflicted with the mate-guarding strategy of high-ranking males. Despite some female mate choice for mid- and low-ranking males and alternative male mating tactics by subordinate males, high-ranking males were able to monopolize most, but not all, within-troop mating and paternity. This result was due in part to the low number of females mating at the same time. The mean number of females displaying mating behaviour per day was 2.42 (range 1-5), and higher-ranking males more successfully monopolized females on days when fewer females were mating. The number of females mating simultaneously influences the outcome of reproductive conflicts between the sexes. Copyright 2001 The Association for the Study of Animal Behaviour JF - Animal Behaviour AU - Soltis, J AU - Thomsen, R AU - Takenaka, O AD - Department of Ecology and Social Behavior, Primate Research Institute, Kyoto University, soltisj@mail.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 485 EP - 494 PB - Academic Press VL - 62 IS - 3 SN - 0003-3472, 0003-3472 KW - Japanese macaque KW - Ecology Abstracts; Animal Behavior Abstracts KW - Social organization KW - Macaca fuscata KW - Paternity KW - Reproductive strategy KW - Social rank KW - Japan KW - Y 25428:Primates KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18099900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Animal+Behaviour&rft.atitle=The+interaction+of+male+and+female+reproductive+strategies+and+paternity+in+wild+Japanese+macaques%2C+Macaca+fuscata&rft.au=Soltis%2C+J%3BThomsen%2C+R%3BTakenaka%2C+O&rft.aulast=Soltis&rft.aufirst=J&rft.date=2001-09-01&rft.volume=62&rft.issue=3&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Macaca fuscata; Japan; Reproductive strategy; Paternity; Social rank; Social organization DO - http://dx.doi.org/10.1006/anbe.2001.1774 ER - TY - JOUR T1 - In Vivo Persistence of Retrovirally Transduced Murine Long-Term Repopulating Cells Is Not Limited by Expression of Foreign Gene Products in the Fully or Minimally Myeloablated Setting AN - 18097028; 5183573 AB - Many nonmalignant hematologic disorders could potentially be treated by genetic correction of as few as 5-10% of target lineage cells. However, immune system clearance of cells expressing gene products perceived as foreign could be limiting. There is evidence that tolerance to foreign proteins can result when myeloablative conditioning is used, but this limits the overall applicability of such techniques. Therefore, we sought to evaluate the engraftment of hematopoietic stem cells carrying a foreign transgene after low-dose irradiation by comparing in vivo survival of murine long-term repopulating cells (LTRC) transduced with either a retroviral vector expressing the bacterial neomycin phosphotransferase gene (neo) or a vector containing neo gene sequences but modified to prevent protein expression (nonexpression). First, marrow cells from congenic donors were transduced with either vector and transplanted into recipients treated with standard dose irradiation of 800 rads. High-level engraftment and gene marking resulted, without differences in the marking levels or pattern of persistence of the cells between cells transduced with either vector. Low-dose irradiation at 100 rads was tested using higher cell doses. Marking levels as high as 10% overall were obtained, again with no differences between mice receiving cells transduced with the neo versus the nonexpression vectors. To investigate a potentially more immunogenic protein, marrow cells were transduced with a vector containing the green fluorescent protein (GFP) gene, and their persistence was studied in recipient mice receiving 100 rads. Stable GFP expression in 5-10% of circulating cells was observed long term. We conclude that even with very low dose conditioning, engraftment by genetically modified LTRC cells at clinically significant levels can be achieved without evidence for clearance of cells known to be expressing immunogenic proteins. JF - Human Gene Therapy AU - Kang, E AU - Giri, N AU - Wu, Tong AU - Sellers, S AU - Kirby, M AU - Hanazono, Yutaka AU - Tisdale, J AU - Dunbar, CE AD - Molecular Hematopoiesis Section, HB, NHLBI, NIH Building 10, Room 7C103, 9000 Rockville Pike, Bethesda, MD 20892, USA, dunbarc@nhlbi.nih.gov Y1 - 2001/09/01/ PY - 2001 DA - 2001 Sep 01 SP - 1663 EP - 1672 VL - 12 IS - 13 SN - 1043-0342, 1043-0342 KW - mice KW - green fluorescent protein KW - neomycin phosphotransferase KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Stem cells KW - Retrovirus KW - Radiation KW - Gene therapy KW - Gene transfer KW - Hemopoiesis KW - Transduction KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18097028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=In+Vivo+Persistence+of+Retrovirally+Transduced+Murine+Long-Term+Repopulating+Cells+Is+Not+Limited+by+Expression+of+Foreign+Gene+Products+in+the+Fully+or+Minimally+Myeloablated+Setting&rft.au=Kang%2C+E%3BGiri%2C+N%3BWu%2C+Tong%3BSellers%2C+S%3BKirby%2C+M%3BHanazono%2C+Yutaka%3BTisdale%2C+J%3BDunbar%2C+CE&rft.aulast=Kang&rft.aufirst=E&rft.date=2001-09-01&rft.volume=12&rft.issue=13&rft.spage=1663&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Transduction; Gene transfer; Gene therapy; Expression vectors; Stem cells; Hemopoiesis; Radiation; Retrovirus ER - TY - JOUR T1 - Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine AN - 17922283; 5165443 AB - Recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine- induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN- gamma co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN- gamma , even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens. JF - Journal of General Virology AU - Johnson, T R AU - Fischer, JE AU - Graham, B S AD - Departments of Microbiology and Immunology and Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA, bgraham@nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 2107 EP - 2116 VL - 82 IS - 9 SN - 0022-1317, 0022-1317 KW - BALB/c mice KW - C57BL/6 mice KW - safety KW - immunogenicity KW - vectors KW - G glycoprotein KW - gamma -Interferon KW - glycoprotein G KW - respiratory syncytial virus KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - ^g-Interferon KW - Respiratory syncytial virus KW - Vaccinia virus KW - Cytokines KW - Glycoproteins KW - Vaccines KW - W3 33365:Vaccines (other) KW - V 22099:Immune response & immune mechanisms KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17922283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+General+Virology&rft.atitle=Construction+and+characterization+of+recombinant+vaccinia+viruses+co-expressing+a+respiratory+syncytial+virus+protein+and+a+cytokine&rft.au=Johnson%2C+T+R%3BFischer%2C+JE%3BGraham%2C+B+S&rft.aulast=Johnson&rft.aufirst=T&rft.date=2001-09-01&rft.volume=82&rft.issue=9&rft.spage=2107&rft.isbn=&rft.btitle=&rft.title=Journal+of+General+Virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Respiratory syncytial virus; Vaccines; Cytokines; Glycoproteins ER - TY - JOUR T1 - Borrelia burgdorferi RevA Antigen Is a Surface-Exposed Outer Membrane Protein Whose Expression Is Regulated in Response to Environmental Temperature and pH AN - 17920074; 5157349 AB - Borrelia burgdorferi, the causative agent of Lyme disease, produces RevA protein during the early stages of mammalian infection. B. burgdorferi apparently uses temperature as a cue to its location, producing proteins required for infection of warm-blooded animals at temperatures corresponding to host body temperature, but does not produce such virulence factors at cooler, ambient temperatures. We have observed that B. burgdorferi regulates expression of RevA in response to temperature, with the protein being synthesized by bacteria cultivated at 34 degree C but not by those grown at 23 degree C. Tissues encountered by B. burgdorferi during its infectious cycle vary in their pH values, and the level of RevA expression was also found to be dependent upon pH of the culture medium. The cellular localization of RevA was also analyzed. Borrelial inner and outer membranes were purified by isopycnic centrifugation, and membrane fractions were conclusively identified by immunoblot analysis using antibodies raised against the integral inner membrane protein MotB and outer membrane-associated Erp lipoproteins. Immunoblot analyses indicated that RevA is located in the B. burgdorferi outer membrane. These analyses also demonstrated that an earlier report (H. A. Bledsoe et al., Infect. Immun. 176:7447-7455, 1994) had misidentified such B. burgdorferi membrane fractions. RevA was further demonstrated to be exposed to the external environment, where it could facilitate interactions with host tissues. JF - Infection and Immunity AU - Carroll, JA AU - El-Hage, N AU - Miller, J C AU - Babb, K AU - Stevenson, B AD - for James A. Carroll: Microscopy Branch, Rocky Mountain Laboratories, NIAID, NIH, 903 South Fourth St., Hamilton, MT 59840., jcarroll@niaid.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 5286 EP - 5293 VL - 69 IS - 9 SN - 0019-9567, 0019-9567 KW - animal models KW - Borrelia burgdorferi KW - MotB protein KW - RevA protein KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Immunoblotting KW - Outer membranes KW - Membrane proteins KW - Environmental factors KW - Centrifugation KW - Antibodies KW - Inner membranes KW - pH effects KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17920074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Borrelia+burgdorferi+RevA+Antigen+Is+a+Surface-Exposed+Outer+Membrane+Protein+Whose+Expression+Is+Regulated+in+Response+to+Environmental+Temperature+and+pH&rft.au=Carroll%2C+JA%3BEl-Hage%2C+N%3BMiller%2C+J+C%3BBabb%2C+K%3BStevenson%2C+B&rft.aulast=Carroll&rft.aufirst=JA&rft.date=2001-09-01&rft.volume=69&rft.issue=9&rft.spage=5286&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.9.5286-5293.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Temperature effects; pH effects; Environmental factors; Outer membranes; Antibodies; Membrane proteins; Inner membranes; Centrifugation; Immunoblotting DO - http://dx.doi.org/10.1128/IAI.69.9.5286-5293.2001 ER - TY - JOUR T1 - Release of Compact Nucleoids with Characteristic Shapes from Escherichia coli AN - 17910572; 5152527 AB - The genomic DNA of bacteria is contained in one or a few compact bodies known as nucleoids. We describe a simple procedure that retains the general shape and compaction of nucleoids from Escherichia coli upon cell lysis and nucleoid release from the cell envelope. The procedure is a modification of that used for the preparation of spermidine nucleoids (nucleoids released in the presence of spermidine) (T. Kornberg, A. Lockwood, and A. Worcel, Proc. Natl. Acad. Sci. USA 71:3189-3193, 1974). Polylysine is added to prevent the normal decompaction of nucleoids which occurs upon cell lysis. Nucleoids retained their characteristic shapes in lysates of exponential-phase cells or in lysates of cells treated with chloramphenicol or nalidixate to alter nucleoid morphology. The notably unstable nucleoids of rifampin-treated cells were obtained in compact, stable form in such lysates. Nucleoids released in the presence of polylysine were easily processed and provided well-defined DNA fluorescence and phase-contrast images. Uniform populations of nucleoids retaining characteristic shapes could be isolated after formaldehyde fixation and heating with sodium dodecyl sulfate. JF - Journal of Bacteriology AU - Zimmerman, S B AU - Murphy, L D AD - National Institutes of Health, Building 5, Room 328W, Bethesda, MD 20892-0560., stevenz@bdg5.niddk.nih.gov Y1 - 2001/09// PY - 2001 DA - Sep 2001 SP - 5041 EP - 5049 VL - 183 IS - 17 SN - 0021-9193, 0021-9193 KW - chloramphenicol KW - nalidixate KW - nalidixic acid KW - polylysine KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Rifampin KW - Fluorescence KW - Escherichia coli KW - Nucleoids KW - J 02721:Cell cycle, morphology and motility KW - N 14920:Chromatin & chromosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17910572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Release+of+Compact+Nucleoids+with+Characteristic+Shapes+from+Escherichia+coli&rft.au=Zimmerman%2C+S+B%3BMurphy%2C+L+D&rft.aulast=Zimmerman&rft.aufirst=S&rft.date=2001-09-01&rft.volume=183&rft.issue=17&rft.spage=5041&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.183.17.5041-5049.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Nucleoids; Rifampin; Fluorescence DO - http://dx.doi.org/10.1128/JB.183.17.5041-5049.2001 ER - TY - JOUR T1 - DNA polymerase beta -mediated long patch base excision repair. Poly(ADP-ribose)polymerase-1 stimulates strand displacement DNA synthesis. AN - 71127407; 11440997 AB - Recently, photoaffinity labeling experiments with mouse cell extracts suggested that PARP-1 functions as a surveillance protein for a stalled BER intermediate. To further understand the role of PARP-1 in BER, we examined the DNA synthesis and flap excision steps in long patch BER using a reconstituted system containing a 34-base pair BER substrate and five purified human enzymes: uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta, flap endonuclease-1 (FEN-1), and PARP-1. PARP-1 stimulates strand displacement DNA synthesis by DNA polymerase beta in this system; this stimulation is dependent on the presence of FEN-1. PARP-1 and FEN-1, therefore, cooperate to activate long patch BER. The results are discussed in the context of a model for BER sub-pathway choice, illustrating a dual role for PARP-1 as a surveillance protein for a stalled BER intermediate and an activating factor for long patch BER DNA synthesis. JF - The Journal of biological chemistry AU - Prasad, R AU - Lavrik, O I AU - Kim, S J AU - Kedar, P AU - Yang, X P AU - Vande Berg, B J AU - Wilson, S H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/08/31/ PY - 2001 DA - 2001 Aug 31 SP - 32411 EP - 32414 VL - 276 IS - 35 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Endodeoxyribonucleases KW - EC 3.1.- KW - Flap Endonucleases KW - FEN1 protein, human KW - EC 3.1.11.- KW - DNA Glycosylases KW - EC 3.2.2.- KW - N-Glycosyl Hydrolases KW - Uracil-DNA Glycosidase KW - Index Medicus KW - Humans KW - Circular Dichroism KW - Endodeoxyribonucleases -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - N-Glycosyl Hydrolases -- metabolism KW - Oligodeoxyribonucleotides -- chemistry KW - Recombinant Proteins -- chemistry KW - Oligodeoxyribonucleotides -- metabolism KW - Amino Acid Substitution KW - DNA Replication KW - Protein Conformation KW - DNA Repair KW - DNA -- metabolism KW - DNA Polymerase beta -- chemistry KW - DNA -- chemistry KW - Poly(ADP-ribose) Polymerases -- metabolism KW - DNA -- biosynthesis KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71127407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=DNA+polymerase+beta+-mediated+long+patch+base+excision+repair.+Poly%28ADP-ribose%29polymerase-1+stimulates+strand+displacement+DNA+synthesis.&rft.au=Prasad%2C+R%3BLavrik%2C+O+I%3BKim%2C+S+J%3BKedar%2C+P%3BYang%2C+X+P%3BVande+Berg%2C+B+J%3BWilson%2C+S+H&rft.aulast=Prasad&rft.aufirst=R&rft.date=2001-08-31&rft.volume=276&rft.issue=35&rft.spage=32411&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional interaction of p53 and BLM DNA helicase in apoptosis. AN - 71125036; 11399766 AB - The Bloom syndrome (BS) protein, BLM, is a member of the RecQ DNA helicase family that also includes the Werner syndrome protein, WRN. Inherited mutations in these proteins are associated with cancer predisposition of these patients. We recently discovered that cells from Werner syndrome patients displayed a deficiency in p53-mediated apoptosis and WRN binds to p53. Here, we report that analogous to WRN, BLM also binds to p53 in vivo and in vitro, and the C-terminal domain of p53 is responsible for the interaction. p53-mediated apoptosis is defective in BS fibroblasts and can be rescued by expression of the normal BLM gene. Moreover, lymphoblastoid cell lines (LCLs) derived from BS donors are resistant to both gamma-radiation and doxorubicin-induced cell killing, and sensitivity can be restored by the stable expression of normal BLM. In contrast, BS cells have a normal Fas-mediated apoptosis, and in response to DNA damage normal accumulation of p53, normal induction of p53 responsive genes, and normal G(1)-S and G(2)-M cell cycle arrest. BLM localizes to nuclear foci referred to as PML nuclear bodies (NBs). Cells from Li-Fraumeni syndrome patients carrying p53 germline mutations and LCLs lacking a functional p53 have a decreased accumulation of BLM in NBs, whereas isogenic lines with functional p53 exhibit normal accumulation. Certain BLM mutants (C1055S or Delta133-237) that have a reduced ability to localize to the NBs when expressed in normal cells can impair the localization of wild type BLM to NBs and block p53-mediated apoptosis, suggesting a dominant-negative effect. Taken together, our results indicate both a novel mechanism of p53 function by which p53 mediates nuclear trafficking of BLM to NBs and the cooperation of p53 and BLM to induce apoptosis. JF - The Journal of biological chemistry AU - Wang, X W AU - Tseng, A AU - Ellis, N A AU - Spillare, E A AU - Linke, S P AU - Robles, A I AU - Seker, H AU - Yang, Q AU - Hu, P AU - Beresten, S AU - Bemmels, N A AU - Garfield, S AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/08/31/ PY - 2001 DA - 2001 Aug 31 SP - 32948 EP - 32955 VL - 276 IS - 35 SN - 0021-9258, 0021-9258 KW - Recombinant Proteins KW - 0 KW - Tumor Suppressor Protein p53 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Bloom syndrome protein KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - Index Medicus KW - Reference Values KW - Gamma Rays KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Fibroblasts -- cytology KW - Dose-Response Relationship, Radiation KW - Binding Sites KW - Cell Survival KW - Fibroblasts -- physiology KW - Transfection KW - Recombinant Proteins -- metabolism KW - Genes, Reporter KW - Cell Nucleus -- physiology KW - Fibroblasts -- radiation effects KW - Cell Line KW - DNA Helicases -- chemistry KW - DNA Helicases -- metabolism KW - DNA Damage KW - Cell Cycle -- physiology KW - Apoptosis -- physiology KW - Apoptosis -- radiation effects KW - Adenosine Triphosphatases -- metabolism KW - Tumor Suppressor Protein p53 -- chemistry KW - Bloom Syndrome -- genetics KW - Adenosine Triphosphatases -- chemistry KW - Tumor Suppressor Protein p53 -- metabolism KW - Bloom Syndrome -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71125036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+interaction+of+p53+and+BLM+DNA+helicase+in+apoptosis.&rft.au=Wang%2C+X+W%3BTseng%2C+A%3BEllis%2C+N+A%3BSpillare%2C+E+A%3BLinke%2C+S+P%3BRobles%2C+A+I%3BSeker%2C+H%3BYang%2C+Q%3BHu%2C+P%3BBeresten%2C+S%3BBemmels%2C+N+A%3BGarfield%2C+S%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=2001-08-31&rft.volume=276&rft.issue=35&rft.spage=32948&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malaria: Cooperative silencing elements in var genes AN - 1520380081; 13694808 AB - Each Plasmodium falciparum malaria parasite carries about 50 var genes from a diverse family that encode variable adhesion proteins on the infected red blood cells of the host, but individual parasites single out just one var gene for expression and silence all the others. Here we show that this silencing is established during the DNA-synthesis phase (S phase) of the cell cycle and that it depends on the cooperative interaction between two elements in separate control regions of each var gene (the 5'-flanking region and the intron). This finding should help to clarify the mechanisms by which parasites coordinate the silencing and activation of var genes that are responsible for antigenic variation in malaria. JF - Nature AU - Deitsch, Kirk W AU - Calderwood, Michael S AU - Wellems, Thomas E AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA Y1 - 2001/08/30/ PY - 2001 DA - 2001 Aug 30 SP - 875 EP - 876 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 412 IS - 6850 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality KW - Parasites KW - Human diseases KW - var gene KW - Cell cycle KW - Erythrocytes KW - Malaria KW - Plasmodium falciparum KW - Hosts KW - Endoparasites KW - Adhesion KW - Public health KW - Genes KW - S phase KW - Introns KW - Transcription activation KW - K 03350:Immunology KW - Q1 08485:Species interactions: pests and control KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1520380081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Malaria%3A+Cooperative+silencing+elements+in+var+genes&rft.au=Deitsch%2C+Kirk+W%3BCalderwood%2C+Michael+S%3BWellems%2C+Thomas+E&rft.aulast=Deitsch&rft.aufirst=Kirk&rft.date=2001-08-30&rft.volume=412&rft.issue=6850&rft.spage=875&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35091146 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-04-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Parasites; Human diseases; Genes; Erythrocytes; Malaria; Hosts; Endoparasites; Adhesion; Public health; var gene; S phase; Cell cycle; Introns; Transcription activation; Plasmodium falciparum DO - http://dx.doi.org/10.1038/35091146 ER - TY - JOUR T1 - Global differential gene expression in response to growth temperature alteration in group A Streptococcus. AN - 71137596; 11517341 AB - Pathogens are exposed to different temperatures during an infection cycle and must regulate gene expression accordingly. However, the extent to which virulent bacteria alter gene expression in response to temperatures encountered in the host is unknown. Group A Streptococcus (GAS) is a human-specific pathogen that is responsible for illnesses ranging from superficial skin infections and pharyngitis to severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. GAS survives and multiplies at different temperatures during human infection. DNA microarray analysis was used to investigate the influence of temperature on global gene expression in a serotype M1 strain grown to exponential phase at 29 degrees C and 37 degrees C. Approximately 9% of genes were differentially expressed by at least 1.5-fold at 29 degrees C relative to 37 degrees C, including genes encoding transporter proteins, proteins involved in iron homeostasis, transcriptional regulators, phage-associated proteins, and proteins with no known homologue. Relatively few known virulence genes were differentially expressed at this threshold. However, transcription of 28 genes encoding proteins with predicted secretion signal sequences was altered, indicating that growth temperature substantially influences the extracellular proteome. TaqMan real-time reverse transcription-PCR assays confirmed the microarray data. We also discovered that transcription of genes encoding hemolysins, and proteins with inferred roles in iron regulation, transport, and homeostasis, was influenced by growth at 40 degrees C. Thus, GAS profoundly alters gene expression in response to temperature. The data delineate the spectrum of temperature-regulated gene expression in an important human pathogen and provide many unforeseen lines of pathogenesis investigation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Smoot, L M AU - Smoot, J C AU - Graham, M R AU - Somerville, G A AU - Sturdevant, D E AU - Migliaccio, C A AU - Sylva, G L AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA. Y1 - 2001/08/28/ PY - 2001 DA - 2001 Aug 28 SP - 10416 EP - 10421 VL - 98 IS - 18 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Hemolysin Proteins KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Streptococcal Infections -- microbiology KW - Humans KW - Gene Expression KW - Hemolysin Proteins -- genetics KW - Temperature KW - Transcription, Genetic KW - Homeostasis KW - Iron -- metabolism KW - Virulence -- genetics KW - In Vitro Techniques KW - Oxidative Stress KW - Genes, Bacterial KW - Streptococcus pyogenes -- growth & development KW - Streptococcus pyogenes -- genetics KW - Streptococcus pyogenes -- pathogenicity KW - Streptococcus pyogenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71137596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Global+differential+gene+expression+in+response+to+growth+temperature+alteration+in+group+A+Streptococcus.&rft.au=Smoot%2C+L+M%3BSmoot%2C+J+C%3BGraham%2C+M+R%3BSomerville%2C+G+A%3BSturdevant%2C+D+E%3BMigliaccio%2C+C+A%3BSylva%2C+G+L%3BMusser%2C+J+M&rft.aulast=Smoot&rft.aufirst=L&rft.date=2001-08-28&rft.volume=98&rft.issue=18&rft.spage=10416&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-08-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Res Microbiol. 1994 May;145(4):269-72 [7997640] Mol Microbiol. 1993 Sep;9(6):1213-22 [7934934] Science. 1995 Jul 28;269(5223):496-512 [7542800] Infect Immun. 1995 Nov;63(11):4535-9 [7591099] Infect Immun. 1995 Nov;63(11):4540-2 [7591100] Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4409-14 [8633080] Infect Immun. 1996 Jun;64(6):1956-60 [8675293] Mol Microbiol. 1996 Sep;21(5):1001-17 [8885270] Gene. 1996 Oct 31;178(1-2):119-23 [8921902] Infect Immun. 1996 Dec;64(12):5399-402 [8945594] Biochem Biophys Res Commun. 1996 Dec 13;229(2):635-42 [8954950] Med Microbiol Immunol. 1996 Nov;185(3):171-81 [9007823] J Bacteriol. 1997 Mar;179(5):1452-9 [9045799] Infect Immun. 1997 Sep;65(9):3606-14 [9284126] Microbiology. 1998 Apr;144 ( Pt 4):1033-44 [9579077] J Bacteriol. 1998 Jun;180(11):2836-41 [9603869] Mol Microbiol. 1998 Oct;30(1):1-6 [9786180] J Mol Biol. 1998 Oct 30;283(3):537-47 [9784364] Infect Immun. 1999 Apr;67(4):1715-22 [10085009] J Bacteriol. 1999 Jun;181(12):3649-57 [10368137] Infect Immun. 1999 Jul;67(7):3367-75 [10377114] Microbiology. 2000 Mar;146 ( Pt 3):659-68 [10746769] Microbes Infect. 2000 Feb;2(2):157-66 [10742688] Biosci Biotechnol Biochem. 2000 May;64(5):1106-9 [10879495] Clin Microbiol Rev. 2000 Jul;13(3):470-511 [10885988] Cell. 2000 Jul 7;102(1):109-26 [10929718] Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9659-64 [10931941] Annu Rev Microbiol. 2000;54:881-941 [11018148] Infect Immun. 2001 Jan;69(1):534-7 [11119547] Mol Microbiol. 2001 Jan;39(2):392-406 [11136460] Infect Immun. 2001 Feb;69(2):822-31 [11159974] EMBO J. 2001 Apr 2;20(7):1681-91 [11285232] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4658-63 [11296296] J Infect Dis. 1973 Oct;128(4):506-13 [4200591] Eur J Biochem. 1974 Sep 16;47(3):469-74 [4215654] Science. 1979 Jan 26;203(4378):374-6 [760197] Rev Infect Dis. 1981 Nov-Dec;3(6):1127-38 [7043704] Microb Pathog. 1989 Jul;7(1):1-10 [2682128] Microbiol Rev. 1989 Dec;53(4):517-30 [2531838] J Bacteriol. 1992 Jan;174(1):1-7 [1729202] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3217-21 [1565612] J Bacteriol. 1992 Sep;174(17):5693-701 [1512202] Clin Microbiol Rev. 1993 Apr;6(2):137-49 [8472246] J Bacteriol. 1993 Dec;175(24):7901-9 [7504666] Mol Microbiol. 1994 Oct;14(2):191-7 [7830565] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human Ca(2+) receptor extracellular domain. Analysis of function of lobe I loop deletion mutants. AN - 71101200; 11399760 AB - The G protein-coupled Ca(2+) receptor (CaR) possesses an approximately 600-residue extracellular domain involved in ligand binding and receptor activation. Based on an alignment of the amino acid sequence of the CaR with that of bacterial periplasmic-binding proteins, the first approximately 530 residues of the extracellular domain are believed to form a domain resembling a bilobed Venus's flytrap (VFT). Four insertions in the CaR sequence that do not align with those of bacterial periplasmic-binding proteins correspond to four loops within lobe I of the VFT. We constructed a series of deletion mutants of these four loops and tested their ability to form fully processed CaR as well as their ability to be activated by Ca(2+). As many as 21 residues (365) of loop III could be deleted without impairing receptor expression or activation. Deletion of portions of either loops I (50) or IV (438) did not impair receptor expression but significantly reduced Ca(2+) activation. Deletion of the entire loop II (117) abolished receptor expression and function, but the replacement of even a single residue within this deletion mutant led to expression of a monomeric form of the receptor showing increased Ca(2+) sensitivity but reduced maximal activation. Our results reveal that certain residues within loops I and IV are dispensable in formation of the VFT domain but are critical for Ca(2+) activation of the receptor. In contrast, the residues in loop II are critical for maintaining the inactive state of the CaR. We discuss these results in light of the recently defined crystal structure of the homologous domain of the type 1 metabotropic glutamate receptor. JF - The Journal of biological chemistry AU - Reyes-Cruz, G AU - Hu, J AU - Goldsmith, P K AU - Steinbach, P J AU - Spiegel, A M AD - Molecular Pathophysiology Section, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. guadeluper@intra.niddk.nih.gov Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 SP - 32145 EP - 32151 VL - 276 IS - 34 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - Index Medicus KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cell Line KW - Mutagenesis, Site-Directed KW - Calcium-Binding Proteins -- physiology KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- chemistry KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71101200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Human+Ca%282%2B%29+receptor+extracellular+domain.+Analysis+of+function+of+lobe+I+loop+deletion+mutants.&rft.au=Reyes-Cruz%2C+G%3BHu%2C+J%3BGoldsmith%2C+P+K%3BSteinbach%2C+P+J%3BSpiegel%2C+A+M&rft.aulast=Reyes-Cruz&rft.aufirst=G&rft.date=2001-08-24&rft.volume=276&rft.issue=34&rft.spage=32145&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Impact of establishing a stroke center at a community hospital on the use of thrombolytic therapy: The NINDS-suburban hospital stroke center experience AN - 39487322; 3625902 AU - Rodriguez, SU AU - DeGraba, T AU - Hamm, T AU - Nyquist, P AU - Hallenbeck, J AU - Warach, S Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39487322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Impact+of+establishing+a+stroke+center+at+a+community+hospital+on+the+use+of+thrombolytic+therapy%3A+The+NINDS-suburban+hospital+stroke+center+experience&rft.au=Rodriguez%2C+SU%3BDeGraba%2C+T%3BHamm%2C+T%3BNyquist%2C+P%3BHallenbeck%2C+J%3BWarach%2C+S&rft.aulast=Rodriguez&rft.aufirst=SU&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Heart Association, 7272 Greenville Avenue, Dallas, Texas 75231-4596, USA; email: strokeconference@heart.org; URL: www.strokeconference.org. Poster Paper No. P192 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Ancient proteins of remarkable plasticity secure prosperity of +RNA viruses AN - 39444544; 3622114 AU - Gorbalenya, A Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39444544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Ancient+proteins+of+remarkable+plasticity+secure+prosperity+of+%2BRNA+viruses&rft.au=Gorbalenya%2C+A&rft.aulast=Gorbalenya&rft.aufirst=A&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Institut Pasteur, 25-28 Rue du Dr Roux, Paris, 75015, France; URL: www.pasteur.fr/externe N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Opportunities and challenges in conducting research in the former Soviet Union AN - 39429984; 3619640 AU - Ron, E Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39429984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Opportunities+and+challenges+in+conducting+research+in+the+former+Soviet+Union&rft.au=Ron%2C+E&rft.aulast=Ron&rft.aufirst=E&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - New single nucleotide polymorphisms in the shear responsive MCP-1 promoter region in atherosclerosis AN - 39424652; 3623110 AU - Nyquist, P A AU - Hamm, T AU - Nagle, J AU - Kauffman, D AU - DeGraba, T J Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39424652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=New+single+nucleotide+polymorphisms+in+the+shear+responsive+MCP-1+promoter+region+in+atherosclerosis&rft.au=Nyquist%2C+P+A%3BHamm%2C+T%3BNagle%2C+J%3BKauffman%2C+D%3BDeGraba%2C+T+J&rft.aulast=Nyquist&rft.aufirst=P&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Heart Association, 7272 Greenville Avenue, Dallas, Texas 75231-4596, USA; email: strokeconference@heart.org; URL: www.strokeconference.org. Poster Paper No. P160 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Molecular genetics and perinatal epidemiology AN - 39421590; 3619561 AU - Wilcox, A Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39421590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Molecular+genetics+and+perinatal+epidemiology&rft.au=Wilcox%2C+A&rft.aulast=Wilcox&rft.aufirst=A&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - What we know about occupational cancer and how we found out AN - 39420124; 3619579 AU - Blair, A Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39420124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=What+we+know+about+occupational+cancer+and+how+we+found+out&rft.au=Blair%2C+A&rft.aulast=Blair&rft.aufirst=A&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Neglected designs in epidemiology AN - 39419680; 3619446 AU - Weinberg, C Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39419680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Neglected+designs+in+epidemiology&rft.au=Weinberg%2C+C&rft.aulast=Weinberg&rft.aufirst=C&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Renal flares in patients with proliferative lupus nephritis (LN): Long-term follow-up of patients participating in randomized controlled studies of pulse immunosuppressive therapy (IST) AN - 39417054; 3614604 AU - Takada, K AU - Parkin, D AU - Austin, HA AU - Crane, M AU - Yarboro, CH AU - Vaughan, E M AU - Kuroiwa, T AU - Danning, CL AU - Klippel, J H AU - Balow, JE AU - Boumpas, D T AU - Illei, G G Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39417054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Renal+flares+in+patients+with+proliferative+lupus+nephritis+%28LN%29%3A+Long-term+follow-up+of+patients+participating+in+randomized+controlled+studies+of+pulse+immunosuppressive+therapy+%28IST%29&rft.au=Takada%2C+K%3BParkin%2C+D%3BAustin%2C+HA%3BCrane%2C+M%3BYarboro%2C+CH%3BVaughan%2C+E+M%3BKuroiwa%2C+T%3BDanning%2C+CL%3BKlippel%2C+J+H%3BBalow%2C+JE%3BBoumpas%2C+D+T%3BIllei%2C+G+G&rft.aulast=Takada&rft.aufirst=K&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Arnold Publishers, URL: www.arnolpublishers.com/journals. Poster Paper No. 16 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Combining pulse cyclophosphamide (CY) with pulse methylprednisolone (MP) improves long-term renal outcome in patients with lupus nephritis (LN) without added toxicity AN - 39408169; 3614879 AU - Illei, G G AU - Austin, HA AU - Crane, M AU - Collins, L AU - Gourley, M F AU - Yarboro, CH AU - Vaughan, E M AU - Kuroiwa, T AU - Danning, CL AU - Steinberg, AD Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39408169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Mechanisms+that+initiate+spontaneous+network+activity+in+the+developing+chick+spinal+cord.&rft.au=Wenner%2C+P%3BO%27Donovan%2C+M+J&rft.aulast=Wenner&rft.aufirst=P&rft.date=2001-09-01&rft.volume=86&rft.issue=3&rft.spage=1481&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Arnold Publishers, URL: www.arnolpublishers.com/journals. Paper No. 36 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Physiological phenotypes of estrogen receptor knock-out mice AN - 39404507; 3618806 AU - Korach, K S Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39404507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Physiological+phenotypes+of+estrogen+receptor+knock-out+mice&rft.au=Korach%2C+K+S&rft.aulast=Korach&rft.aufirst=K&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Animal Science, 1111 N. Dunlap Ave., Savoy, IL 61874, USA; phone: 217-356-3182; fax: 217-398-4119; URL: www.asas.org. Paper No. 418 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Irox promotes neurogenesis adjacent to the MHB domain while its repression within the MHB is critical for the MHB development AN - 39402270; 3613001 AU - Itoh, M Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 1200:Aquatic Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39402270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Irox+promotes+neurogenesis+adjacent+to+the+MHB+domain+while+its+repression+within+the+MHB+is+critical+for+the+MHB+development&rft.au=Itoh%2C+M&rft.aulast=Itoh&rft.aufirst=M&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=IDEAS+Working+Paper+Series+from+RePEc&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 14th International Congress of Developmental Biology, Congress Bldg., 3-6-13 Awajimachi, Chuo-ku, Osaka 541-0047, Japan; fax: 81-6-6221-3071; email: isdb@congre.co.jp; URL: www.congre.co.jp/icdb. Poster Paper No. S8-P63 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Repressor activity of headless/Tcf3 is essential for vertebrate head formation AN - 39398467; 3612591 AU - Kim, C-H Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 1200:Aquatic Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39398467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Repressor+activity+of+headless%2FTcf3+is+essential+for+vertebrate+head+formation&rft.au=Kim%2C+C-H&rft.aulast=Kim&rft.aufirst=C-H&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 14th International Congress of Developmental Biology, Congress Bldg., 3-6-13 Awajimachi, Chuo-ku, Osaka 541-0047, Japan; fax: 81-6-6221-3071; email: isdb@congre.co.jp; URL: www.congre.co.jp/icdb. Paper No. S3-6 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Effects of CBE screening on breast cancer mortality - U.S. HIP data AN - 39396275; 3619453 AU - Simpson, N AU - Prorok, P Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39396275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Effects+of+CBE+screening+on+breast+cancer+mortality+-+U.S.+HIP+data&rft.au=Simpson%2C+N%3BProrok%2C+P&rft.aulast=Simpson&rft.aufirst=N&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Applying new genomic technology in epidemiologic studies AN - 39353763; 3619590 AU - Taylor, J Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39353763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Applying+new+genomic+technology+in+epidemiologic+studies&rft.au=Taylor%2C+J&rft.aulast=Taylor&rft.aufirst=J&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Biological and methodological issues for nutritional biomarkers: An overview AN - 39350986; 3619557 AU - Potischman, N Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39350986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Biological+and+methodological+issues+for+nutritional+biomarkers%3A+An+overview&rft.au=Potischman%2C+N&rft.aulast=Potischman&rft.aufirst=N&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Design of genetic epidemiology studies AN - 39346370; 3619591 AU - Wacholder, S Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39346370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Design+of+genetic+epidemiology+studies&rft.au=Wacholder%2C+S&rft.aulast=Wacholder&rft.aufirst=S&rft.date=2001-08-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Canadian Society for Epidemiology and Biostatistics, ; URL: www.cseb.ca N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Constitutively Dead, Conditionally Live HIV-1 Genomes: Ex vivo Implications for a Live Virus Vaccine AN - 17901333; 5163140 AB - An effective vaccine against AIDS is unlikely to be available for many years. As we approach two decades since the first identification of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical trials. The subunit approach has been criticized for its inability to elicit effectively cytotoxic T-lymphocyte (CTL) response, which is felt by many to be needed for protection against HIV-1 infection. In subhuman primates, a live attenuated simian immunodeficiency virus (SIV) vaccine candidate, capable of inducing CTL, has been found to confer prophylactic immunity sufficient to prevent simian AIDS. Because replication competent (live) attenuated viruses could over time revert to virulence, such a live attenuated approach has largely been dismissed for HIV-1. Here, we describe the creation of constitutively dead conditionally live (CDCL) HIV-1 genomes. These genomes are constitutively defective for the Tat/TAR axis and are conditionally dependent on tetracycline for attenuated replication with robust expression of viral antigens. Our results suggest that CDCL genomes merit consideration as safer "live" attenuated HIV-1 vaccine candidates. JF - Journal of Biological Chemistry AU - Smith, S M AU - Khoroshev, M AU - Marx, P A AU - Orenstein, J AU - Jeang, K T AD - New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07102, USA, kj7e@nih.gov Y1 - 2001/08/24/ PY - 2001 DA - 2001 Aug 24 SP - 32184 EP - 32190 VL - 276 IS - 34 SN - 0021-9258, 0021-9258 KW - HIV-1 KW - SIV KW - Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Attenuation KW - Killer cells KW - Immunity KW - Tetracyclines KW - Human immunodeficiency virus 1 KW - Vaccines KW - Simian immunodeficiency virus KW - A 01097:Viruses KW - V 22003:AIDS: Immunological aspects KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Constitutively+Dead%2C+Conditionally+Live+HIV-1+Genomes%3A+Ex+vivo+Implications+for+a+Live+Virus+Vaccine&rft.au=Smith%2C+S+M%3BKhoroshev%2C+M%3BMarx%2C+P+A%3BOrenstein%2C+J%3BJeang%2C+K+T&rft.aulast=Smith&rft.aufirst=S&rft.date=2001-08-24&rft.volume=276&rft.issue=34&rft.spage=32184&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Simian immunodeficiency virus; Human immunodeficiency virus 1; Tetracyclines; Vaccines; Attenuation; Immunity; Killer cells ER - TY - JOUR T1 - Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. AN - 71100764; 11511139 AB - Controlled trials in lupus nephritis have demonstrated that cyclophosphamide therapy is superior to corticosteroid therapy alone. The long-term effectiveness and side-effect profiles of pulse immunosuppressive regimens warrant further study. To define the long-term risk and benefit of monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both. Extended follow-up (median, 11 years) of a randomized, controlled trial. U.S. government research hospital. 82 patients with proliferative lupus nephritis. Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events. In an intention-to-treat survival analysis, the likelihood of treatment failure was significantly lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002) groups than in the methylprednisolone group. Combination therapy and cyclophosphamide therapy alone did not differ statistically in terms of effectiveness or adverse events. Of patients who completed the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combination group than in the cyclophosphamide group (relative risk, 0.095 [95% CI, 0.01 to 0.842]). With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide and methylprednisolone appears to provide additional benefit over pulse cyclophosphamide alone and does not confer additional risk for adverse events. JF - Annals of internal medicine AU - Illei, G G AU - Austin, H A AU - Crane, M AU - Collins, L AU - Gourley, M F AU - Yarboro, C H AU - Vaughan, E M AU - Kuroiwa, T AU - Danning, C L AU - Steinberg, A D AU - Klippel, J H AU - Balow, J E AU - Boumpas, D T AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 9S-205, Bethesda, MD 20892, USA. illeig@exchange.nih.gov Y1 - 2001/08/21/ PY - 2001 DA - 2001 Aug 21 SP - 248 EP - 257 VL - 135 IS - 4 SN - 0003-4819, 0003-4819 KW - Anti-Inflammatory Agents KW - 0 KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Creatinine KW - AYI8EX34EU KW - Prednisone KW - VB0R961HZT KW - Methylprednisolone KW - X4W7ZR7023 KW - Abridged Index Medicus KW - Index Medicus KW - Treatment Failure KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Prednisone -- therapeutic use KW - Creatinine -- blood KW - Drug Therapy, Combination KW - Adult KW - Follow-Up Studies KW - Female KW - Male KW - Remission Induction KW - Survival Analysis KW - Cyclophosphamide -- administration & dosage KW - Methylprednisolone -- administration & dosage KW - Lupus Nephritis -- drug therapy KW - Lupus Nephritis -- blood KW - Anti-Inflammatory Agents -- adverse effects KW - Anti-Inflammatory Agents -- administration & dosage KW - Lupus Nephritis -- mortality KW - Methylprednisolone -- adverse effects KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71100764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Oncogenic+mutants+of+RON+and+MET+receptor+tyrosine+kinases+cause+activation+of+the+beta-catenin+pathway.&rft.au=Danilkovitch-Miagkova%2C+A%3BMiagkov%2C+A%3BSkeel%2C+A%3BNakaigawa%2C+N%3BZbar%2C+B%3BLeonard%2C+E+J&rft.aulast=Danilkovitch-Miagkova&rft.aufirst=A&rft.date=2001-09-01&rft.volume=21&rft.issue=17&rft.spage=5857&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 2001 Aug 21;135(4):296-8 [11511144] Ann Intern Med. 2002 Sep 17;137(6):545-6; author reply 545-6 [12230360] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases steady-state estrogen receptor- beta mRNA levels after CYP1A1 and CYP1B1 reduction in rat granulosa cells in vitro AN - 18290173; 5349037 AB - Previous in-vitro investigations of rat granulosa cells (GC) have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits estrogen secretion and FSH-induced aromatase activity. Although TCDD exerted no effect on basal aromatase enzyme activity, TCDD did reduce steady-state aromatase mRNA levels in GC using competitive RT-PCR. TCDD is hypothesized to induce these changes through aromatic hydrocarbon receptor (AHR)-mediated gene transcription and the modulation of the estrogen receptor (ER)-signaling pathway. In this study we show that rat GC express mRNA for AHR and the AHR nuclear translocator (ARNT) as well as biomarkers of TCDD action, CYP1A1 and CYP1B1 mRNA. Basal CYP1A1 and ER- alpha mRNAs were present only in trace amounts. By relative RT-PCR analysis we showed that CYP1A1 and CYP1B1 mRNA were induced significantly by TCDD at 6 h and that induction of CYP1A1 was maintained throughout the experiment. Using competitive RT-PCR, we observed no significant change in the mRNA levels of ARNT between control and TCDD-treated GC. Both AHR and ER- beta mRNA levels increased significantly at 48 h with TCDD compared with controls. Since ER- beta mRNA was not increased significantly until 48 h in culture, we suggest that in rat GC, the observed ER- beta mRNA increase by TCDD might be a result of CYP1A1/CYP1B1 catalyzed estrogen metabolism and aromatase mRNA inhibition via AHR. JF - Molecular and Cellular Endocrinology AU - Dasmahapatra, A K AU - Wimpee, BAB AU - Trewin, AL AU - Hutz, R J AD - Department of Biological Sciences, 308 Lapham Hall, 3209 North Maryland Avenue, and NIEHS Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA, rjhutz@uwm.edu Y1 - 2001/08/20/ PY - 2001 DA - 2001 Aug 20 SP - 39 EP - 48 VL - 182 IS - 1 SN - 0303-7207, 0303-7207 KW - rats KW - CYP1A1 protein KW - CYP1B1 protein KW - Toxicology Abstracts KW - Granulosa cells KW - TCDD KW - Estrogen receptors KW - mRNA KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18290173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Cellular+Endocrinology&rft.atitle=2%2C3%2C7%2C8-Tetrachlorodibenzo-p-dioxin+increases+steady-state+estrogen+receptor-+beta+mRNA+levels+after+CYP1A1+and+CYP1B1+reduction+in+rat+granulosa+cells+in+vitro&rft.au=Dasmahapatra%2C+A+K%3BWimpee%2C+BAB%3BTrewin%2C+AL%3BHutz%2C+R+J&rft.aulast=Dasmahapatra&rft.aufirst=A&rft.date=2001-08-20&rft.volume=182&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - TCDD; mRNA; Estrogen receptors; Granulosa cells ER - TY - JOUR T1 - Human DNA polymerase iota promiscuous mismatch extension. AN - 71083944; 11402031 AB - Human DNA polymerase iota is a low-fidelity template copier that preferentially catalyzes the incorporation of the wobble base G, rather than the Watson-Crick base A, opposite template T (Tissier, A., McDonald, J. P., Frank, E. G., and Woodgate, R. (2000) Genes Dev. 14, 1642-1650; Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., and Prakash, L. (2000) Nature 406, 1015-1019; Zhang, Y., Yuan, F., Wu, X., and Wang, Z. (2000) Mol. Cell. Biol. 20, 7099-7108). Here, we report on its ability to extend all 12 possible mispairs and 4 correct pairs in different sequence contexts. Extension from both matched and mismatched primer termini is generally most efficient and accurate when A is the next template base. In contrast, extension occurs less efficiently and accurately when T is the target template base. A striking exception occurs during extension of a G:T mispair, where the enzyme switches specificity, "preferring" to make a correct A:T base pair immediately downstream from an originally favored G:T mispair. Polymerase iota generates a variety of single and tandem mispairs with high frequency, implying that it may act as a strong mutator when copying undamaged DNA templates in vivo. Even so, its limited ability to catalyze extension from a relatively stable primer/template containing a "buried" mismatch suggests that polymerase iota-catalyzed errors are confined to short template regions. JF - The Journal of biological chemistry AU - Vaisman, A AU - Tissier, A AU - Frank, E G AU - Goodman, M F AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, NICHD, National Institutes of Health, Bethesda, Maryland 20892-2725, USA. Y1 - 2001/08/17/ PY - 2001 DA - 2001 Aug 17 SP - 30615 EP - 30622 VL - 276 IS - 33 SN - 0021-9258, 0021-9258 KW - DNA KW - 9007-49-2 KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Humans KW - Catalysis KW - DNA -- metabolism KW - Base Pair Mismatch KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71083944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Human+DNA+polymerase+iota+promiscuous+mismatch+extension.&rft.au=Vaisman%2C+A%3BTissier%2C+A%3BFrank%2C+E+G%3BGoodman%2C+M+F%3BWoodgate%2C+R&rft.aulast=Vaisman&rft.aufirst=A&rft.date=2001-08-17&rft.volume=276&rft.issue=33&rft.spage=30615&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation. AN - 71135851; 11526476 AB - Multiple endocrine neoplasia type 1 is an autosomal dominant tumor syndrome. Manifestations include neoplasms of the parathyroid glands, enteropancreatic neuroendocrine cells, and the anterior pituitary gland. The MEN1 tumor suppressor gene encodes menin, a 610 amino acid nuclear protein without sequence homology to other proteins. To elucidate menin function, we used immunoprecipitation to identify interacting proteins. The NF-kappaB proteins p50, p52 and p65 were found to interact specifically and directly with menin in vitro and in vivo. The region of NF-kappaB proteins sufficient for binding to menin is the N-terminus. Furthermore, amino acids 305-381 of menin are essential for this binding. Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. Also, PMA (phorbol 12-myristate 13-acetate)-stimulated NF-kappaB activation is suppressed by menin. These observations suggest that menin's ability to interact with NF-kappaB proteins and its modulation of NF-kappaB transactivation contribute to menin's tumor suppressor function. JF - Oncogene AU - Heppner, C AU - Bilimoria, K Y AU - Agarwal, S K AU - Kester, M AU - Whitty, L J AU - Guru, S C AU - Chandrasekharappa, S C AU - Collins, F S AU - Spiegel, A M AU - Marx, S J AU - Burns, A L AD - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/08/16/ PY - 2001 DA - 2001 Aug 16 SP - 4917 EP - 4925 VL - 20 IS - 36 SN - 0950-9232, 0950-9232 KW - MEN1 protein, human KW - 0 KW - NF-kappa B KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - COS Cells KW - HeLa Cells KW - Humans KW - Glutathione Transferase -- chemistry KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Structure, Tertiary KW - Precipitin Tests KW - Transcriptional Activation KW - Cell Line KW - NF-kappa B -- chemistry KW - Neoplasm Proteins -- physiology KW - Genes, Tumor Suppressor KW - Neoplasm Proteins -- immunology KW - Neoplasm Proteins -- chemistry KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71135851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+tumor+suppressor+protein+menin+interacts+with+NF-kappaB+proteins+and+inhibits+NF-kappaB-mediated+transactivation.&rft.au=Heppner%2C+C%3BBilimoria%2C+K+Y%3BAgarwal%2C+S+K%3BKester%2C+M%3BWhitty%2C+L+J%3BGuru%2C+S+C%3BChandrasekharappa%2C+S+C%3BCollins%2C+F+S%3BSpiegel%2C+A+M%3BMarx%2C+S+J%3BBurns%2C+A+L&rft.aulast=Heppner&rft.aufirst=C&rft.date=2001-08-16&rft.volume=20&rft.issue=36&rft.spage=4917&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Kit-activating mutation D816V enhances stem cell factor--dependent chemotaxis. AN - 71078447; 11493470 AB - The D816V mutation of c-kit has been detected in patients with mastocytosis. This mutation leads to constitutive tyrosine kinase activation of Kit. Because stem cell factor (SCF), the ligand for Kit (CD117(+)), is a chemoattractant for CD117(+) cells and one feature of mastocytosis is an abnormal collection of mast cells in tissues derived from CD34(+)CD117(+) mast cell precursors, the hypothesis was considered that the D816V mutation would enhance chemotaxis of these precursor cells. Constructs encoding wild-type Kit or Kit bearing the D816V mutation were transfected into Jurkat cells, labeled with Calcein-AM, and migration to SCF assessed in the presence or absence of tyrosine kinase inhibitors. Chemotaxis to SCF was enhanced in D816V transfectants compared to wild-type Kit transfectants (P <.002). Migration of both transfectants was inhibited by tyrosine kinase inhibitors, although D816V transfectants were more sensitive. Chemotaxis was next performed on CD34(+)CD117(+) circulating mast cell precursors obtained from patients with mastocytosis. Analysis of prechemotaxis and migrated cells showed that whereas less than 10% in the prechemotaxis sample had the D816V mutation, 40% to 80% of migrated cells had this mutation. These results demonstrate that the D816V Kit mutation enhances chemotaxis of CD117(+) cells, offering one explanation for increased mast cells observed in tissues of patients with mastocytosis. (Blood. 2001;98:1195-1199) JF - Blood AU - Taylor, M L AU - Dastych, J AU - Sehgal, D AU - Sundstrom, M AU - Nilsson, G AU - Akin, C AU - Mage, R G AU - Metcalfe, D D AD - Laboratory of Allergic Diseases and Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA. mtaylor@niaid.nih.gov Y1 - 2001/08/15/ PY - 2001 DA - 2001 Aug 15 SP - 1195 EP - 1199 VL - 98 IS - 4 SN - 0006-4971, 0006-4971 KW - Antigens, CD34 KW - 0 KW - Enzyme Inhibitors KW - Stem Cell Factor KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-kit KW - Abridged Index Medicus KW - Index Medicus KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Jurkat Cells KW - Enzyme Inhibitors -- pharmacology KW - Drug Synergism KW - Proto-Oncogene Proteins c-kit -- metabolism KW - Mastocytosis -- pathology KW - Mastocytosis -- genetics KW - Chemotaxis -- genetics KW - Stem Cell Factor -- pharmacology KW - Mastocytosis -- etiology KW - Chemotaxis -- drug effects KW - Mutation, Missense KW - Proto-Oncogene Proteins c-kit -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71078447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=The+Kit-activating+mutation+D816V+enhances+stem+cell+factor--dependent+chemotaxis.&rft.au=Taylor%2C+M+L%3BDastych%2C+J%3BSehgal%2C+D%3BSundstrom%2C+M%3BNilsson%2C+G%3BAkin%2C+C%3BMage%2C+R+G%3BMetcalfe%2C+D+D&rft.aulast=Taylor&rft.aufirst=M&rft.date=2001-08-15&rft.volume=98&rft.issue=4&rft.spage=1195&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sir2p exists in two nucleosome-binding complexes with distinct deacetylase activities. AN - 71075556; 11500379 AB - The absolute requirement for the histone deacetylase activity of Sir2p in silencing coupled with the conservation of Sir2p-like proteins in larger eukaryotes suggests that this molecule plays an important role in gene regulation in all organisms. Here we report the purification and characterization of two Sir2p-containing protein complexes; one of which contains Sir4p and the other Net1p. The Sir4p-containing complex has an NAD-dependent histone deacetylase activity, while the Net1p-containing complex possesses deacetylase activity but only weak NAD-dependent histone deacetylase activity. Finally, we demonstrate that the Sir2p-containing complexes bind nucleosomes efficiently and partially restrict accessibility of the linker DNA to enzymatic probes. JF - The EMBO journal AU - Ghidelli, S AU - Donze, D AU - Dhillon, N AU - Kamakaka, R T AD - Unit on Chromatin and Transcription, NICHD/NIH, Building 18T, Room 106, 18 Library Drive, Bethesda, MD 20892, USA. Y1 - 2001/08/15/ PY - 2001 DA - 2001 Aug 15 SP - 4522 EP - 4535 VL - 20 IS - 16 SN - 0261-4189, 0261-4189 KW - Cell Cycle Proteins KW - 0 KW - Fungal Proteins KW - Net1 protein, S cerevisiae KW - Nuclear Proteins KW - Nucleosomes KW - Recombinant Fusion Proteins KW - SIR3 protein, S cerevisiae KW - SIR4 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Silent Information Regulator Proteins, Saccharomyces cerevisiae KW - Trans-Activators KW - SIR2 protein, S cerevisiae KW - EC 3.5.1.- KW - Sirtuin 2 KW - Sirtuins KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Fusion Proteins -- isolation & purification KW - Recombinant Fusion Proteins -- genetics KW - Nuclear Proteins -- metabolism KW - Recombinant Fusion Proteins -- physiology KW - Mutagenesis KW - Binding Sites KW - Trans-Activators -- metabolism KW - Fungal Proteins -- physiology KW - Histone Deacetylases -- isolation & purification KW - Nucleosomes -- metabolism KW - Histone Deacetylases -- physiology KW - Fungal Proteins -- genetics KW - Fungal Proteins -- isolation & purification KW - Trans-Activators -- isolation & purification KW - Fungal Proteins -- metabolism KW - Trans-Activators -- genetics KW - Histone Deacetylases -- metabolism KW - Trans-Activators -- physiology KW - Histone Deacetylases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71075556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Sir2p+exists+in+two+nucleosome-binding+complexes+with+distinct+deacetylase+activities.&rft.au=Ghidelli%2C+S%3BDonze%2C+D%3BDhillon%2C+N%3BKamakaka%2C+R+T&rft.aulast=Ghidelli&rft.aufirst=S&rft.date=2001-08-15&rft.volume=20&rft.issue=16&rft.spage=4522&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1999 Dec;19(12):7944-50 [10567520] Mol Cell Biol. 1995 Oct;15(10):5294-303 [7565678] Cell. 1999 Dec 23;99(7):735-45 [10619427] Nature. 2000 Feb 17;403(6771):795-800 [10693811] J Cell Biol. 2000 May 1;149(3):575-90 [10791972] J Cell Biol. 2000 May 15;149(4):811-24 [10811823] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807-11 [10811920] EMBO J. 2000 Jun 1;19(11):2641-51 [10835361] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6658-63 [10841563] Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14178-82 [11106374] Mol Cell. 2000 Oct;6(4):769-80 [11090616] EMBO J. 2001 Mar 15;20(6):1353-62 [11250901] Cell. 2001 May 4;105(3):403-14 [11348596] Eur J Biochem. 1980 Dec;112(3):501-11 [7460934] Cell. 1982 Sep;30(2):567-78 [6215985] Cell. 1982 Nov;31(1):183-92 [6297747] Mol Cell Biol. 1986 Feb;6(2):688-702 [3023863] Genetics. 1987 May;116(1):9-22 [3297920] Mol Cell Biol. 1987 Dec;7(12):4441-52 [3325825] Cell. 1988 Oct 7;55(1):27-39 [3048701] Science. 1990 Feb 16;247(4944):841-5 [2106160] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6286-90 [2201024] Mol Cell Biol. 1990 Sep;10(9):4932-4 [2117703] EMBO J. 1990 Dec;9(12):3997-4006 [2249661] Cell. 1991 Sep 20;66(6):1279-87 [1913809] Genes Dev. 1992 Feb;6(2):186-96 [1737615] Proc Natl Acad Sci U S A. 1992 May 1;89(9):4062-5 [1570334] Genes Dev. 1995 Dec 1;9(23):2888-902 [7498786] Mol Cell Biol. 1996 Aug;16(8):4349-56 [8754835] Cell. 1996 Aug 23;86(4):667-77 [8752220] Nature. 1996 Sep 5;383(6595):92-6 [8779721] EMBO J. 1996 Sep 16;15(18):4959-69 [8890169] Genes Dev. 1997 Jan 1;11(1):83-93 [9000052] Genes Dev. 1997 Jan 15;11(2):241-54 [9009206] Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2186-91 [9122169] Trends Biochem Sci. 1997 Apr;22(4):124-8 [9149531] Curr Opin Cell Biol. 1997 Jun;9(3):383-7 [9159071] Chromosoma. 1997 Aug;106(3):136-48 [9233987] Mol Cell Biol. 1997 Dec;17(12):7061-8 [9372937] EMBO J. 1997 Nov 3;16(21):6495-509 [9351831] J Biol Chem. 1998 Apr 17;273(16):9388-92 [9545262] Mol Cell Biol. 1998 Sep;18(9):5392-403 [9710623] J Biol Chem. 1999 Jan 22;274(4):1928-33 [9890947] Genes Dev. 1999 Mar 15;13(6):698-708 [10090726] Cell. 1999 Apr 16;97(2):233-44 [10219244] Cell. 1999 Apr 16;97(2):245-56 [10219245] Methods Enzymol. 1999;304:715-25 [10372392] EMBO J. 1992 Jun;11(6):2201-9 [1600945] Genes Dev. 1993 Apr;7(4):592-604 [8458576] Genes Dev. 1993 Jul;7(7A):1133-45 [8319906] Nature. 1994 May 19;369(6477):245-7 [8183346] Science. 1994 Jun 17;264(5166):1768-71 [8209257] Science. 1994 Jul 1;265(5168):53-60 [8016655] Cold Spring Harb Symp Quant Biol. 1993;58:247-56 [7956035] Genes Dev. 1994 Oct 1;8(19):2257-69 [7958893] Cell. 1995 Feb 24;80(4):583-92 [7867066] J Biol Chem. 1999 Dec 31;274(53):37795-9 [10608841] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro generation and transplantation of precursor-derived human dopamine neurons. AN - 71064479; 11494363 AB - The use of in vitro expanded human CNS precursors has the potential to overcome some of the ethical, logistic and technical problems of fetal tissue transplantation in Parkinson disease. Cultured rat mesencephalic precursors proliferate in response to bFGF and upon mitogen withdrawal, differentiate into functional dopamine neurons that alleviate motor symptoms in Parkinsonian rats (Studer et al. [1998] Nat. Neurosci. 1:290-295). The successful clinical application of CNS precursor technology in Parkinson disease will depend on the efficient in vitro generation of human dopaminergic neurons. We demonstrate that human dopamine neurons can be generated from both midbrain and cortical precursors. Transplantation of midbrain precursor-derived dopamine neurons into Parkinsonian rats resulted in grafts rich in tyrosine hydroxylase positive neurons 6 weeks after transplantation. No surviving tyrosine hydroxylase positive neurons could be detected when dopamine neurons derived from cortical precursors were grafted. Our data demonstrate in vitro derivation of human dopamine neurons from expanded CNS precursors and encourage further studies that systematically address in vivo function and clinical potential. Copyright 2001 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Sánchez-Pernaute, R AU - Studer, L AU - Bankiewicz, K S AU - Major, E O AU - McKay, R D AD - Laboratory of Molecular Medicine and Neuroscience, NINDS, NIH, Bethesda, Maryland, USA. Y1 - 2001/08/15/ PY - 2001 DA - 2001 Aug 15 SP - 284 EP - 288 VL - 65 IS - 4 SN - 0360-4012, 0360-4012 KW - Sympathomimetics KW - 0 KW - Oxidopamine KW - 8HW4YBZ748 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Humans KW - Fetus -- cytology KW - Cell Differentiation KW - Disease Models, Animal KW - Cell Survival KW - Rats KW - Rats, Sprague-Dawley KW - Stem Cells -- cytology KW - Cells, Cultured KW - Cell Culture Techniques -- methods KW - Female KW - Parkinsonian Disorders -- chemically induced KW - Neurons -- cytology KW - Dopamine -- physiology KW - Parkinsonian Disorders -- surgery KW - Brain Tissue Transplantation KW - Stem Cell Transplantation KW - Neurons -- transplantation KW - Fetal Tissue Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71064479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=In+vitro+generation+and+transplantation+of+precursor-derived+human+dopamine+neurons.&rft.au=S%C3%A1nchez-Pernaute%2C+R%3BStuder%2C+L%3BBankiewicz%2C+K+S%3BMajor%2C+E+O%3BMcKay%2C+R+D&rft.aulast=S%C3%A1nchez-Pernaute&rft.aufirst=R&rft.date=2001-08-15&rft.volume=65&rft.issue=4&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro assembly of feline immunodeficiency virus capsid protein: biological role of conserved cysteines. AN - 71061309; 11488604 AB - Core assembly, a key step in the retroviral life cycle, is poorly understood. Previous studies have shown that the entire gag region is needed to form the assembled particles. In this report, we have shown that the assembly process is driven by recombinant capsid protein (p26) of feline immunodeficiency virus itself. Proteins are expressed in a bacterial system and soluble forms of wild-type and modified proteins are purified from bacterial extracts and are examined on gel-filtration chromatography fitted to an HPLC system. It has also been shown that changing residue Cys190 (one of the two conserved cysteines of feline immunodeficiency virus which are also conserved for all the immunodeficiency viruses including HIV) to serine by site-directed mutagenesis disrupts the assembly process. In addition, this modification causes considerable thermal instability of the protein while substitutions at nonconserved cysteines do not significantly affect the thermal stability and assembly of the protein. These findings indicate that conserved cysteine residues play a vital role in the capsid protein assembly and, therefore, are critical for virus infectivity. Copyright 2001 Academic Press. JF - Archives of biochemistry and biophysics AU - Nath, M D AU - Peterson, D L AD - National Cancer Institute, NIH, Frederick, Maryland 21702, USA. nathm@ncifcrf.gov Y1 - 2001/08/15/ PY - 2001 DA - 2001 Aug 15 SP - 287 EP - 294 VL - 392 IS - 2 SN - 0003-9861, 0003-9861 KW - Disulfides KW - 0 KW - RNA, Messenger KW - Recombinant Proteins KW - Sulfhydryl Compounds KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Immunoblotting KW - Escherichia coli -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Temperature KW - Amino Acid Sequence KW - Protein Binding KW - Chromatography, High Pressure Liquid KW - Mutagenesis, Site-Directed KW - RNA, Messenger -- metabolism KW - Chromatography, Gel KW - Recombinant Proteins -- metabolism KW - Sulfhydryl Compounds -- chemistry KW - Protein Folding KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Time Factors KW - Calorimetry, Differential Scanning KW - Mutation KW - Cysteine -- chemistry KW - Immunodeficiency Virus, Feline -- chemistry KW - Capsid -- chemistry KW - Cysteine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71061309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=In+vitro+assembly+of+feline+immunodeficiency+virus+capsid+protein%3A+biological+role+of+conserved+cysteines.&rft.au=Nath%2C+M+D%3BPeterson%2C+D+L&rft.aulast=Nath&rft.aufirst=M&rft.date=2001-08-15&rft.volume=392&rft.issue=2&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Projection structure and molecular architecture of OxlT, a bacterial membrane transporter AN - 18166116; 5157804 AB - The major facilitator superfamily (MFS) represents the largest collection of evolutionarily related members within the class of membrane 'carrier proteins. OxlT, a representative example of the MFS, is an oxalate-transporting membrane protein in Oxalobacter formigenes. From an electron crystallographic analysis of two- dimensional crystals of OxlT, we have determined the projection structure of this membrane transporter. The projection map at 6 Aa resolution indicates the presence of 12 transmembrane helices in each monomer of OxlT, with one set of six helices related to the other set by an approximate internal two-fold axis. The projection map reveals the existence of a central cavity, which we propose to be part of the pathway of oxalate transport. By combining information from the projection map with related biochemical data, we present probable models for the architectural arrangement of transmembrane helices in this protein superfamily. JF - EMBO Journal AU - Heymann, JAW AU - Sarker, R AU - Hirai, T AU - Shi, D AU - Milne, JLS AU - Maloney, P C AU - Subramaniam, S AD - Laboratorie of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, ss1@nih.gov Y1 - 2001/08/15/ PY - 2001 DA - 2001 Aug 15 SP - 4408 EP - 4413 VL - 20 IS - 16 SN - 0261-4189, 0261-4189 KW - OxlT protein KW - transporters KW - Microbiology Abstracts B: Bacteriology KW - Oxalobacter formigenes KW - Cell membranes KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18166116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Projection+structure+and+molecular+architecture+of+OxlT%2C+a+bacterial+membrane+transporter&rft.au=Heymann%2C+JAW%3BSarker%2C+R%3BHirai%2C+T%3BShi%2C+D%3BMilne%2C+JLS%3BMaloney%2C+P+C%3BSubramaniam%2C+S&rft.aulast=Heymann&rft.aufirst=JAW&rft.date=2001-08-15&rft.volume=20&rft.issue=16&rft.spage=4408&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Oxalobacter formigenes; Cell membranes ER - TY - JOUR T1 - Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene. AN - 71093553; 11481455 AB - Brain glucose utilization is markedly depressed in adult rats made cretinous after birth. To ascertain which subtype of thyroid hormone (TH) receptors, TRalpha1 or TRbeta, is involved in the regulation of glucose utilization during brain development, we used the 2-[(14)C]deoxyglucose method in mice with a mutation in either their TRalpha or TRbeta gene. A C insertion produced a frameshift mutation in their carboxyl terminus. These mutants lacked TH binding and transactivation activities and exhibited potent dominant negative activity. Glucose utilization in the homozygous TRbetaPV mutant mice and their wild-type siblings was almost identical in 19 brain regions, whereas it was markedly reduced in all brain regions of the heterozygous TRalpha1PV mice. These suggest that the alpha1 receptor mediates the TH effects in brain. Inasmuch as local cerebral glucose utilization is closely related to local synaptic activity, we also examined which thyroid hormone receptor is involved in the expression of synaptotagmin-related gene 1 (Srg1), a TH-positively regulated gene involved in the formation and function of synapses [Thompson, C. C. (1996) J. Neurosci. 16, 7832-7840]. Northern analysis showed that Srg1 expression was markedly reduced in the cerebellum of TRalpha(PV/+) mice but not TRbeta(PV/PV) mice. These results show that the same receptor, TRalpha1, is involved in the regulation by TH of both glucose utilization and Srg1 expression. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Itoh, Y AU - Esaki, T AU - Kaneshige, M AU - Suzuki, H AU - Cook, M AU - Sokoloff, L AU - Cheng, S Y AU - Nunez, J AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, and National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4030, USA. Y1 - 2001/08/14/ PY - 2001 DA - 2001 Aug 14 SP - 9913 EP - 9918 VL - 98 IS - 17 SN - 0027-8424, 0027-8424 KW - Membrane Proteins KW - 0 KW - Nerve Tissue Proteins KW - Protein Isoforms KW - Receptors, Thyroid Hormone KW - Sytl1 protein, mouse KW - Thyroid Hormones KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Nerve Tissue Proteins -- physiology KW - Animals KW - Age Factors KW - Cerebral Cortex -- metabolism KW - Mice KW - Protein Isoforms -- physiology KW - Membrane Proteins -- genetics KW - Nerve Tissue Proteins -- genetics KW - Protein Isoforms -- deficiency KW - Mice, Knockout KW - Cerebellum -- metabolism KW - Gene Expression Regulation -- genetics KW - Frameshift Mutation KW - Nerve Tissue Proteins -- deficiency KW - Thyroid Hormones -- physiology KW - Membrane Proteins -- biosynthesis KW - Transcriptional Activation -- genetics KW - Deoxyglucose -- pharmacokinetics KW - Protein Isoforms -- genetics KW - Gene Targeting KW - Glycolysis -- genetics KW - Mutation KW - Mutagenesis, Insertional KW - Receptors, Thyroid Hormone -- deficiency KW - Glucose -- metabolism KW - Receptors, Thyroid Hormone -- physiology KW - Receptors, Thyroid Hormone -- genetics KW - Energy Metabolism -- genetics KW - Brain -- metabolism KW - Brain -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71093553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Brain+glucose+utilization+in+mice+with+a+targeted+mutation+in+the+thyroid+hormone+alpha+or+beta+receptor+gene.&rft.au=Itoh%2C+Y%3BEsaki%2C+T%3BKaneshige%2C+M%3BSuzuki%2C+H%3BCook%2C+M%3BSokoloff%2C+L%3BCheng%2C+S+Y%3BNunez%2C+J&rft.aulast=Itoh&rft.aufirst=Y&rft.date=2001-08-14&rft.volume=98&rft.issue=17&rft.spage=9913&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Endocrinol Metab. 2000 Jan-Feb;11(1):6-10 [10652499] Annu Rev Physiol. 2000;62:439-66 [10845098] Curr Opin Struct Biol. 2001 Apr;11(2):163-73 [11297924] Sci Basis Med Annu Rev. 1966;:317-39 [5327143] J Neurochem. 1977 May;28(5):897-916 [864466] J Cereb Blood Flow Metab. 1981;1(1):7-36 [7035471] Ann Neurol. 1982 Mar;11(3):233-46 [7092177] Ann Neurol. 1982 Oct;12(4):333-40 [7149659] J Physiol (Paris). 1982-1983;78(7):603-52 [6194291] Brain Res. 1986 May 14;373(1-2):139-45 [3719302] Nature. 1986 Dec 18-31;324(6098):635-40 [2879242] Nature. 1986 Dec 18-31;324(6098):641-6 [2879243] Neuroscience. 1986 Dec;19(4):1217-26 [3822116] Mol Endocrinol. 1987 Jan;1(1):83-9 [2842662] Mol Endocrinol. 1988 Oct;2(10):893-901 [2903438] Nature. 1989 Jul 20;340(6230):242-4 [2569164] J Neurosci. 1989 Sep;9(9):3347-58 [2795167] EMBO J. 1991 Feb;10(2):269-75 [1991448] J Clin Invest. 1991 Dec;88(6):2123-30 [1661299] Mol Endocrinol. 1991 Sep;5(9):1339-50 [1663215] J Neurosci. 1992 Jun;12(6):2288-302 [1607941] Eur J Endocrinol. 1994 Jan;130(1):15-24 [8124475] Mol Endocrinol. 1994 Jun;8(6):746-56 [7935490] Eur J Endocrinol. 1995 Oct;133(4):390-8 [7581959] Mol Med. 1995 Mar;1(3):306-19 [8529109] Nat Genet. 1996 Jul;13(3):354-7 [8673137] J Mol Neurosci. 1996 Fall;7(3):229-34 [8906618] Thyroid. 1996 Oct;6(5):497-504 [8936679] J Neurosci. 1996 Dec 15;16(24):7832-40 [8987811] EMBO J. 1997 Jul 16;16(14):4412-20 [9250685] Endocr Rev. 1997 Aug;18(4):462-75 [9267760] EMBO J. 1998 Jan 15;17(2):455-61 [9430637] Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15758-62 [9861043] Endocrinology. 1999 Jan;140(1):335-43 [9886843] Neurochem Res. 1999 Feb;24(2):321-9 [9972882] Oncogene. 1999 Jan 28;18(4):917-24 [10023667] Genes Dev. 1999 May 15;13(10):1329-41 [10346821] Am J Physiol. 1999 Jun;276(6 Pt 2):H2006-12 [10362681] Am J Physiol Regul Integr Comp Physiol. 2000 Jun;278(6):R1545-54 [10848522] Cereb Cortex. 2000 Oct;10(10):939-45 [11007544] Mol Cell Biol. 2000 Nov;20(22):8329-42 [11046130] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13209-14 [11069286] Trends Endocrinol Metab. 2000 Aug;11(6):207-11 [10878749] Thyroid. 2000 Jan;10(1):41-52 [10691312] J Biol Chem. 2000 Apr 14;275(15):11507-13 [10753970] Nat Neurosci. 2000 May;3(5):472-5 [10769387] Nature. 2001 Mar 1;410(6824):41-9 [11242035] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53. AN - 71091470; 11481424 AB - The p33ING1 protein is a regulator of cell cycle, senescence, and apoptosis. Three alternatively spliced transcripts of p33ING1 encode p47ING1a, p33ING1b, and p24ING1c. We cloned an additional ING family member, p33ING2/ING1L. Unlike p33ING1b, p33ING2 is induced by the DNA-damaging agents etoposide and neocarzinostatin. p33ING1b and p33ING2 negatively regulate cell growth and survival in a p53-dependent manner through induction of G(1)-phase cell-cycle arrest and apoptosis. p33ING2 strongly enhances the transcriptional-transactivation activity of p53. Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382. Taken together, p33ING2 is a DNA damage-inducible gene that negatively regulates cell proliferation through activation of p53 by enhancing its acetylation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Nagashima, M AU - Shiseki, M AU - Miura, K AU - Hagiwara, K AU - Linke, S P AU - Pedeux, R AU - Wang, X W AU - Yokota, J AU - Riabowol, K AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/08/14/ PY - 2001 DA - 2001 Aug 14 SP - 9671 EP - 9676 VL - 98 IS - 17 SN - 0027-8424, 0027-8424 KW - Homeodomain Proteins KW - 0 KW - ING2 protein, human KW - Receptors, Cytoplasmic and Nuclear KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - Bleomycin KW - 11056-06-7 KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Zinostatin KW - 9014-02-2 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Bleomycin -- pharmacology KW - Etoposide -- pharmacology KW - Gamma Rays KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Cells, Cultured -- radiation effects KW - Transcription, Genetic KW - Amino Acid Sequence KW - Cells, Cultured -- drug effects KW - Zinostatin -- pharmacology KW - Tumor Cells, Cultured -- radiation effects KW - Cloning, Molecular KW - Acetylation KW - Doxorubicin -- pharmacology KW - Molecular Sequence Data KW - Cisplatin -- pharmacology KW - Gene Expression Regulation -- drug effects KW - G1 Phase KW - Tumor Stem Cell Assay KW - Cell Division KW - Homeodomain Proteins -- isolation & purification KW - Homeodomain Proteins -- genetics KW - DNA Damage KW - Apoptosis -- physiology KW - Protein Processing, Post-Translational KW - Homeodomain Proteins -- physiology KW - Apoptosis -- drug effects KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71091470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=DNA+damage-inducible+gene+p33ING2+negatively+regulates+cell+proliferation+through+acetylation+of+p53.&rft.au=Nagashima%2C+M%3BShiseki%2C+M%3BMiura%2C+K%3BHagiwara%2C+K%3BLinke%2C+S+P%3BPedeux%2C+R%3BWang%2C+X+W%3BYokota%2C+J%3BRiabowol%2C+K%3BHarris%2C+C+C&rft.aulast=Nagashima&rft.aufirst=M&rft.date=2001-08-14&rft.volume=98&rft.issue=17&rft.spage=9671&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF053537; GENBANK; AF078835 N1 - SuppNotes - Cited By: Cell. 1994 Mar 25;76(6):1013-23 [8137420] Nature. 1992 Jul 2;358(6381):15-6 [1614522] Cell. 1995 Jan 27;80(2):293-9 [7834749] Oncogene. 1995 Mar 16;10(6):1053-9 [7700629] Trends Biochem Sci. 1995 Feb;20(2):56-9 [7701562] Nat Genet. 1995 Jun;10(2):188-95 [7663514] Genes Chromosomes Cancer. 1995 Jul;13(3):163-7 [7669735] Cancer Res. 1995 Oct 1;55(19):4420-4 [7671255] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8876-80 [7568035] Genes Dev. 1996 May 1;10(9):1054-72 [8654922] Cancer Res. 1996 Mar 1;56(5):1146-50 [8640775] Nat Genet. 1996 Dec;14(4):415-20 [8944021] Nucleic Acids Res. 1996 Dec 15;24(24):4859-67 [9016654] Cell. 1997 Mar 7;88(5):593-602 [9054499] Mol Cell Biol. 1997 Apr;17(4):2014-9 [9121449] Cancer Res. 1997 Apr 1;57(7):1255-8 [9102209] J Biol Chem. 1997 May 2;272(18):12181-8 [9115291] Cytogenet Cell Genet. 1997;76(3-4):176-8 [9186514] Nature. 1997 Jun 19;387(6635):823-7 [9194565] Adv Pharmacol. 1997;41:429-60 [9204155] Cell. 1997 Jun 27;89(7):1175-84 [9215639] Cell. 1997 Aug 22;90(4):595-606 [9288740] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Mol Cell Biol. 1997 Oct;17(10):6087-96 [9315668] Cell. 1997 Oct 31;91(3):325-34 [9363941] Nature. 1998 Jan 15;391(6664):295-8 [9440695] Science. 1998 Sep 11;281(5383):1674-7 [9733514] Science. 1998 Sep 11;281(5383):1677-9 [9733515] Genes Dev. 1998 Sep 15;12(18):2831-41 [9744860] Genes Dev. 1998 Oct 1;12(19):2973-83 [9765199] Mol Cell Biol. 1999 Feb;19(2):1202-9 [9891054] Cancer Res. 1999 Feb 15;59(4):843-8 [10029073] EMBO J. 1999 Mar 1;18(5):1397-406 [10064605] Curr Opin Genet Dev. 1999 Feb;9(1):40-8 [10072350] Cytogenet Cell Genet. 1998;83(3-4):232-5 [10072587] FEBS Lett. 1999 May 7;450(3):197-204 [10359074] Genes Chromosomes Cancer. 1999 Jul;25(3):284-9 [10379875] Br J Cancer. 1999 Apr;80(1-2):59-66 [10389978] Genes Dev. 1999 Oct 1;13(19):2490-501 [10521394] EMBO J. 1999 Nov 15;18(22):6455-61 [10562557] Genes Chromosomes Cancer. 2000 Mar;27(3):319-22 [10679922] J Hum Genet. 2000;45(3):177-81 [10807544] Mol Cell Biol. 2000 Jun;20(11):3807-16 [10805724] Cancer Res. 2000 Jun 15;60(12):3143-6 [10866301] Cell. 2000 Sep 15;102(6):849-62 [11030628] Br J Cancer. 2000 Dec;83(11):1468-72 [11076655] Nature. 1992 Jul 2;358(6381):83-6 [1614538] Genes Dev. 1992 Jul;6(7):1143-52 [1628822] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3988-92 [8387205] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Br J Cancer. 1994 Mar;69(3):409-16 [8123467] EMBO J. 2001 Feb 15;20(4):914-23 [11179235] J Biol Chem. 2001 Mar 23;276(12):8734-9 [11118440] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 [1946467] Genes Dev. 1994 Nov 1;8(21):2540-51 [7958916] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense DNAs as multisite genomic modulators identified by DNA microarray AN - 17919224; 5157747 AB - Antisense oligodeoxynucleotides can selectively block disease-causing genes, and cancer genes have been chosen as potential targets for antisense drugs to treat cancer. However, nonspecific side effects have clouded the true antisense mechanism of action and hampered clinical development of antisense therapeutics. Using DNA microarrays, we have conducted a systematic characterization of gene expression in cells exposed to antisense, either exogenously or endogenously. Here, we show that in a sequence-specific manner, antisense targeted to protein kinase A RI alpha alters expression of the clusters of coordinately expressed genes at a specific stage of cell growth, differentiation, and activation. The genes that define the proliferation-transformation signature are down-regulated, whereas those that define the differentiation-reverse transformation signature are up-regulated in antisense-treated cancer cells and tumors, but not in host livers. In this differentiation signature, the genes showing the highest induction include genes for the G proteins Rap1 and Cdc42. The expression signature induced by the exogenously supplied antisense oligodeoxynucleotide overlaps strikingly with that induced by endogenous antisense gene overexpression. Defining antisense DNAs on the basis of their effects on global gene expression can lead to identification of clinically relevant antisense therapeutics and can identify which molecular and cellular events might be important in complex biological processes, such as cell growth and differentiation. JF - Proceedings of the National Academy of Sciences, USA AU - Cho, Y S AU - Kim, M AU - Cheadle, C AU - Neary, C AU - Becker, K G AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, chochung@helix.nih.gov Y1 - 2001/08/14/ PY - 2001 DA - 2001 Aug 14 SP - 9819 EP - 9823 VL - 98 IS - 17 SN - 0027-8424, 0027-8424 KW - Cdc42 protein KW - DNA microarrays KW - Rap1 protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Protein kinase A KW - Oligonucleotides KW - Gene expression KW - Differentiation KW - Antisense KW - Cell proliferation KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17919224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Antisense+DNAs+as+multisite+genomic+modulators+identified+by+DNA+microarray&rft.au=Cho%2C+Y+S%3BKim%2C+M%3BCheadle%2C+C%3BNeary%2C+C%3BBecker%2C+K+G%3BCho-Chung%2C+Y+S&rft.aulast=Cho&rft.aufirst=Y&rft.date=2001-08-14&rft.volume=98&rft.issue=17&rft.spage=9819&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.171314398 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein kinase A; Differentiation; Cell proliferation; Antisense; Oligonucleotides; Gene expression DO - http://dx.doi.org/10.1073/pnas.171314398 ER - TY - JOUR T1 - Cyproterone acetate induces a cellular tolerance to cadmium in rat liver epithelial cells involving reduced cadmium accumulation. AN - 71162724; 11551428 AB - Several reports indicate that some steroids, in particular sex steroid hormones, can modify cadmium toxicity. We recently reported that cyproterone acetate (CA), a synthetic steroidal antiandrogen that is closely related in structure to progesterone, affects cadmium toxicity in mice. In the present study, we investigated the effect of CA on cadmium toxicity in a rat liver epithelial cell line (TRL 1215) in vitro. Cells were exposed to various concentrations of CA (0,1,10, or 50 microM) for 24 h and subsequently exposed to cadmium (0,50, or 100 microM; as CdCl2) for an additional 24 h. CA pretreatment resulted in a clear decrease in the sensitivity to cadmium. Additional time course study showed CA pretreatment provided protection against cadmium toxicity but only when given for 6 or more hours prior to cadmium exposure. Cellular cadmium accumulation was markedly reduced (60% decrease) in cells pretreated for 6 or more hours with CA. In the presence of protein synthesis inhibitors the protective effect of CA toward cadmium toxicity was abolished. However, in the presence of the GSH synthesis inhibitor, L-buthionine (S,R)-sulfoximide (BSO), the protective effect of CA toward cadmium toxicity remained. CA alone increased metallothionein (MT) levels 2.4-fold, while cadmium (50 microM) alone resulted in a 8.9-fold increase over control. However, cadmium-induced MT synthesis was markedly decreased by CA pretreatment probably because of reduced cadmium accumulation. Analysis of various metal transporters by bDNA signal amplification assay revealed that the ZnT-1 transporter gene, which encodes for a membrane protein associated with zinc efflux, was expressed three-fold more in CA treated cells than control. These data show that CA pretreatment provides protection against cadmium toxicity in vitro and indicate that this protection is due to a decreased accumulation of cadmium rather than through activation of MT synthesis. This decrease of cellular cadmium accumulation appears to be related to events that require protein synthesis and may be due to activation of the genes associated with zinc efflux. JF - Toxicology AU - Takiguchi, M AU - Cherrington, N J AU - Hartley, D P AU - Klaassen, C D AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, MD F0-09, Research Triangle Park, NC 27709, USA. Y1 - 2001/08/13/ PY - 2001 DA - 2001 Aug 13 SP - 13 EP - 25 VL - 165 IS - 1 SN - 0300-483X, 0300-483X KW - Androgen Antagonists KW - 0 KW - Carrier Proteins KW - Oligonucleotide Probes KW - Proteins KW - Cadmium KW - 00BH33GNGH KW - Cyproterone Acetate KW - 4KM2BN5JHF KW - DNA KW - 9007-49-2 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Hepatocytes -- drug effects KW - Carrier Proteins -- metabolism KW - Glutathione -- metabolism KW - Proteins -- metabolism KW - DNA -- biosynthesis KW - Cell Line KW - Hepatocytes -- metabolism KW - Epithelial Cells -- metabolism KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Cadmium -- metabolism KW - Androgen Antagonists -- pharmacology KW - Epithelial Cells -- drug effects KW - Cadmium -- toxicity KW - Cyproterone Acetate -- pharmacology KW - Cadmium -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71162724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Cyproterone+acetate+induces+a+cellular+tolerance+to+cadmium+in+rat+liver+epithelial+cells+involving+reduced+cadmium+accumulation.&rft.au=Takiguchi%2C+M%3BCherrington%2C+N+J%3BHartley%2C+D+P%3BKlaassen%2C+C+D%3BWaalkes%2C+M+P&rft.aulast=Takiguchi&rft.aufirst=M&rft.date=2001-08-13&rft.volume=165&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity in stably tat-transfected HeLa Cells. AN - 71118208; 11522182 AB - The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regulatory protein in the HIV-1 replication cycle. Tat interacts with cellular transcriptional factors and cytokines, such as tumor necrosis factor (TNF-alpha), and alters the expression of a variety of genes in HIV-1-infected and noninfected cells. To further elucidate the mechanisms by which HIV-1 Tat amplifies the activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial (HeLa) cell line. We observed that Tat-expressing cells had increased NF-kappa B-dependent trans-activational activity due to enhanced NF-kappa B--DNA binding in response to TNF-alpha treatment. Tumor necrosis factor receptor (TNFR) p55 was the prominent receptor, as neutralizing antibodies to TNFR p55, but not to TNFR p75, blocked TNF-alpha-mediated NF-kappa B activation. Furthermore, tat-transfected cells were more sensitive to TNF-alpha-induced cytotoxicity and only the neutralizing antibodies to TNFR p55 completely protected the cells. To determine whether TNFR p55 was involved in amplification of cellular response to TNF-alpha by HIV-1 Tat, we investigated the effect of TNF-alpha on TNFR p55 expression in the tat-transfected cells. TNF-alpha treatment resulted in a reduction in both TNFR p55 mRNA and protein levels in the control cells but not in the tat-transfected cells as determined with Northern blot and Western blot analyses, respectively. Our results indicate that HIV-1 Tat may inhibit TNF-alpha-induced repression of TNFR p55 and thereby amplify TNF-alpha activity in these stably transfected cells. JF - AIDS research and human retroviruses AU - Chiao, C AU - Bader, T AU - Stenger, J E AU - Baldwin, W AU - Brady, J AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health and Science, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/08/10/ PY - 2001 DA - 2001 Aug 10 SP - 1125 EP - 1132 VL - 17 IS - 12 SN - 0889-2229, 0889-2229 KW - Antigens, CD KW - 0 KW - Gene Products, tat KW - NF-kappa B KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Type I KW - Tumor Necrosis Factor-alpha KW - tat Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - HIV-1 -- metabolism KW - Blotting, Western KW - Gene Expression Regulation, Viral KW - Transfection KW - HeLa Cells KW - Humans KW - Transcriptional Activation KW - NF-kappa B -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Antigens, CD -- metabolism KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Gene Products, tat -- metabolism KW - Gene Products, tat -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71118208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=HIV+type+1+Tat+inhibits+tumor+necrosis+factor+alpha-induced+repression+of+tumor+necrosis+factor+receptor+p55+and+amplifies+tumor+necrosis+factor+alpha+activity+in+stably+tat-transfected+HeLa+Cells.&rft.au=Chiao%2C+C%3BBader%2C+T%3BStenger%2C+J+E%3BBaldwin%2C+W%3BBrady%2C+J%3BBarrett%2C+J+C&rft.aulast=Chiao&rft.aufirst=C&rft.date=2001-08-10&rft.volume=17&rft.issue=12&rft.spage=1125&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation. AN - 71059688; 11390408 AB - hCds1 (Chk2) is an evolutionarily conserved kinase that functions in DNA damage response and cell cycle checkpoint. The Cds1 family of kinases are activated by a family of large phosphatidylinositol 3-kinase-like kinases. In humans, ataxia telangiectasia-mutated (ATM) and ataxia-telangiectasia and Rad3-related kinases activate hCds1 by phosphorylating Thr(68) . hCds1 and Cds1-related kinases contain the FHA (forkhead-associated) domain, which appears to be important for integrating the DNA damage signal. It is not known how ATM phosphorylation activates hCds1 function and whether the phosphorylation is linked to the FHA. Here, we demonstrate that the hCds1-FHA domain is essential for Thr(68) phosphorylation. Thr(68) phosphorylation, in turn, is required for ionizing radiation-induced autophosphorylation of two amino acid residues in hCds1, Thr(383) and Thr(387). These two amino acid residues, located in the activation loop of hCds1, are conserved in hCds1-related kinases and are essential for hCds1 activity. Thus, the hCds1-FHA domain mediates a chain of phosphorylation events on hCds1, which includes phosphorylation by ATM and hCds1 autophosphorylation, in response to DNA damage. JF - The Journal of biological chemistry AU - Lee, C H AU - Chung, J H AD - Laboratory of Biochemical Genetics, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1654, USA. Y1 - 2001/08/10/ PY - 2001 DA - 2001 Aug 10 SP - 30537 EP - 30541 VL - 276 IS - 32 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Recombinant Fusion Proteins KW - Schizosaccharomyces pombe Proteins KW - Threonine KW - 2ZD004190S KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Protein Kinases KW - EC 2.7.- KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Checkpoint Kinase 2 KW - EC 2.7.1.11 KW - CHEK2 protein, human KW - EC 2.7.11.1 KW - Cds1 protein, S pombe KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Immunoblotting KW - Plasmids -- metabolism KW - Threonine -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - DNA Damage KW - Enzyme Activation KW - Schizosaccharomyces -- metabolism KW - Humans KW - Glutathione Transferase -- metabolism KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Phosphorylation -- radiation effects KW - DNA, Complementary -- metabolism KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Mutation KW - Radiation, Ionizing KW - Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71059688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+hCds1+%28Chk2%29-FHA+domain+is+essential+for+a+chain+of+phosphorylation+events+on+hCds1+that+is+induced+by+ionizing+radiation.&rft.au=Lee%2C+C+H%3BChung%2C+J+H&rft.aulast=Lee&rft.aufirst=C&rft.date=2001-08-10&rft.volume=276&rft.issue=32&rft.spage=30537&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel family of predicted retroviral-like aspartyl proteases with a possible key role in eukaryotic cell cycle control. AN - 71109853; 11516960 JF - Current biology : CB AU - Krylov, D M AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 2001/08/07/ PY - 2001 DA - 2001 Aug 07 SP - R584 EP - R587 VL - 11 IS - 15 SN - 0960-9822, 0960-9822 KW - DDI1 protein, S cerevisiae KW - 0 KW - Fungal Proteins KW - Saccharomyces cerevisiae Proteins KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - Eukaryotic Cells KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Fungal Proteins -- chemistry KW - Retroviridae -- enzymology KW - Fungal Proteins -- physiology KW - Aspartic Acid Endopeptidases -- genetics KW - Cell Cycle -- physiology KW - Aspartic Acid Endopeptidases -- chemistry KW - Fungal Proteins -- genetics KW - Aspartic Acid Endopeptidases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71109853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+biology+%3A+CB&rft.atitle=A+novel+family+of+predicted+retroviral-like+aspartyl+proteases+with+a+possible+key+role+in+eukaryotic+cell+cycle+control.&rft.au=Krylov%2C+D+M%3BKoonin%2C+E+V&rft.aulast=Krylov&rft.aufirst=D&rft.date=2001-08-07&rft.volume=11&rft.issue=15&rft.spage=R584&rft.isbn=&rft.btitle=&rft.title=Current+biology+%3A+CB&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phosphatase catalytically. AN - 71053675; 11387337 AB - MKP-2 is a member of the mitogen-activated protein (MAP) kinase phosphatase family which has been suggested to play an important role in the feedback control of MAP kinase-mediated gene expression. Although MKP-2 preferentially inactivates extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) MAP kinase subfamilies, the mechanisms underlying its own regulation remain unclear. In this report, we have examined the MKP-2 interaction with and catalytic activation by distinct MAP kinase subfamilies. We found that the catalytic activity of MKP-2 was enhanced dramatically by ERK and JNK but was affected only minimally by p38. By contrast, p38 and ERK bound MKP-2 with comparably strong affinities, whereas JNK and MKP-2 interacted very weakly. Through site-directed mutagenesis, we defined the ERK/p38-binding site as a cluster of arginine residues in the NH(2)-terminal domain of MKP-2. Mutation of the basic motif abrogated its interaction with both ERK and p38 and severely compromised the catalytic activation of MKP-2 by these kinases. Unexpectedly, such mutations had little effect on JNK-triggered catalytic activation. Both in vitro and in vivo, wild type MKP-2 effectively inactivated ERK2 whereas MKP-2 mutants incapable of binding to ERK/p38 did not. Finally, in addition to its role as a docking site for ERK and p38, the MKP-2 basic motif plays a role in regulating its nuclear localization. Our studies provided a mechanistic explanation for the substrate preference of MKP-2 and suggest that catalytic activation of MKP-2 upon binding to its substrates is crucial for its function. JF - The Journal of biological chemistry AU - Chen, P AU - Hutter, D AU - Yang, X AU - Gorospe, M AU - Davis, R J AU - Liu, Y AD - Laboratory of Cellular and Molecular Biology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/08/03/ PY - 2001 DA - 2001 Aug 03 SP - 29440 EP - 29449 VL - 276 IS - 31 SN - 0021-9258, 0021-9258 KW - Recombinant Fusion Proteins KW - 0 KW - Recombinant Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinase 8 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Mitogen-Activated Protein Kinase Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - DUSP4 protein, human KW - EC 3.1.3.48 KW - Dual-Specificity Phosphatases KW - Protein Tyrosine Phosphatases KW - Index Medicus KW - Enzyme Activation KW - HeLa Cells KW - Humans KW - Glutathione Transferase -- metabolism KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Kinetics KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Cell Line KW - MAP Kinase Signaling System -- physiology KW - Protein Tyrosine Phosphatases -- metabolism KW - Mitogen-Activated Protein Kinases -- chemistry KW - Mitogen-Activated Protein Kinases -- metabolism KW - Protein Tyrosine Phosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71053675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Discordance+between+the+binding+affinity+of+mitogen-activated+protein+kinase+subfamily+members+for+MAP+kinase+phosphatase-2+and+their+ability+to+activate+the+phosphatase+catalytically.&rft.au=Chen%2C+P%3BHutter%2C+D%3BYang%2C+X%3BGorospe%2C+M%3BDavis%2C+R+J%3BLiu%2C+Y&rft.aulast=Chen&rft.aufirst=P&rft.date=2001-08-03&rft.volume=276&rft.issue=31&rft.spage=29440&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single amino acid substitutions and deletions that alter the G protein coupling properties of the V2 vasopressin receptor identified in yeast by receptor random mutagenesis. AN - 71053512; 11375990 AB - To facilitate structure-function relationship studies of the V2 vasopressin receptor, a prototypical G(s)-coupled receptor, we generated V2 receptor-expressing yeast strains (Saccharomyces cerevisiae) that required arginine vasopressin-dependent receptor/G protein coupling for cell growth. V2 receptors heterologously expressed in yeast were unable to productively interact with the endogenous yeast G protein alpha subunit, Gpa1p, or a mutant Gpa1p subunit containing the C-terminal G alpha(q) sequence (Gq5). In contrast, the V2 receptor efficiently coupled to a Gpa1p/G alpha(s) hybrid subunit containing the C-terminal G alpha(s) sequence (Gs5), indicating that the V2 receptor retained proper G protein coupling selectivity in yeast. To gain insight into the molecular basis underlying the selectivity of V2 receptor/G protein interactions, we used receptor saturation random mutagenesis to generate a yeast library expressing mutant V2 receptors containing mutations within the second intracellular loop. A subsequent yeast genetic screen of about 30,000 mutant receptors yielded four mutant receptors that, in contrast to the wild-type receptor, showed substantial coupling to Gq5. Functional analysis of these mutant receptors, followed by more detailed site-directed mutagenesis studies, indicated that single amino acid substitutions at position Met(145) in the central portion of the second intracellular loop of the V2 receptor had pronounced effects on receptor/G protein coupling selectivity. We also observed that deletion of single amino acids N-terminal of Met(145) led to misfolded receptor proteins, whereas single amino acid deletions C-terminal of Met(145) had no effect on V2 receptor function. These findings highlight the usefulness of combining receptor random mutagenesis and yeast expression technology to study mechanisms governing receptor/G protein coupling selectivity and receptor folding. JF - The Journal of biological chemistry AU - Erlenbach, I AU - Kostenis, E AU - Schmidt, C AU - Serradeil-Le Gal, C AU - Raufaste, D AU - Dumont, M E AU - Pausch, M H AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/08/03/ PY - 2001 DA - 2001 Aug 03 SP - 29382 EP - 29392 VL - 276 IS - 31 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - GTP-Binding Protein alpha Subunits KW - Oligodeoxyribonucleotides KW - Protein Subunits KW - Receptors, Vasopressin KW - Saccharomyces cerevisiae Proteins KW - Arginine Vasopressin KW - 113-79-1 KW - GPA1 protein, S cerevisiae KW - EC 3.6.5.1 KW - GTP-Binding Protein alpha Subunits, Gq-G11 KW - Heterotrimeric GTP-Binding Proteins KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Models, Molecular KW - Humans KW - Oligodeoxyribonucleotides -- genetics KW - Amino Acid Sequence KW - Cell Membrane -- physiology KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Cattle KW - Sequence Alignment KW - Oligodeoxyribonucleotides -- chemistry KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Sequence Deletion KW - Gene Library KW - Saccharomyces cerevisiae -- genetics KW - Arginine Vasopressin -- pharmacology KW - Receptors, Vasopressin -- physiology KW - Saccharomyces cerevisiae -- growth & development KW - Receptors, Vasopressin -- chemistry KW - Heterotrimeric GTP-Binding Proteins -- metabolism KW - Heterotrimeric GTP-Binding Proteins -- chemistry KW - Receptors, Vasopressin -- genetics KW - Saccharomyces cerevisiae -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71053512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Single+amino+acid+substitutions+and+deletions+that+alter+the+G+protein+coupling+properties+of+the+V2+vasopressin+receptor+identified+in+yeast+by+receptor+random+mutagenesis.&rft.au=Erlenbach%2C+I%3BKostenis%2C+E%3BSchmidt%2C+C%3BSerradeil-Le+Gal%2C+C%3BRaufaste%2C+D%3BDumont%2C+M+E%3BPausch%2C+M+H%3BWess%2C+J&rft.aulast=Erlenbach&rft.aufirst=I&rft.date=2001-08-03&rft.volume=276&rft.issue=31&rft.spage=29382&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted gene knockout by 2'-O-aminoethyl modified triplex forming oligonucleotides. AN - 71049401; 11389147 AB - Triplex forming oligonucleotides (TFOs) are of interest because of their potential for facile gene targeting. However, the failure of TFOs to bind target sequences at physiological pH and Mg(2+) concentration has limited their biological applications. Recently, pyrimidine TFOs with 2'-O-aminoethyl (AE) substitutions were shown to have enhanced kinetics and stability of triplex formation (Cuenoud, B., Casset, F., Husken, D., Natt, F., Wolf, R. M., Altmann, K. H., Martin, P., and Moser H. E. (1998) Angew. Chem. Int. Ed. 37, 1288--1291). We have prepared psoralen-linked TFOs with varying amounts of the AE-modified residues, and have characterized them in biochemical assays in vitro, and in stability and HPRT gene knockout assays in vivo. The AE TFOs showed higher affinity for the target in vitro than a TFO with uniform 2'-OMe substitution, with relatively little loss of affinity when the assay was performed in reduced Mg(2+). Once formed they were also more stable in "physiological" buffer, with the greatest affinity and stability displayed by the TFO with all but one residue in the AE format. However, TFOs with lesser amounts of the AE modification formed the most stable triplexes in vivo, and showed the highest HPRT gene knockout activity. We conclude that the AE modification can enhance the biological activity of pyrimidine TFOs, but that extensive substitution is deleterious. JF - The Journal of biological chemistry AU - Puri, N AU - Majumdar, A AU - Cuenoud, B AU - Natt, F AU - Martin, P AU - Boyd, A AU - Miller, P S AU - Seidman, M M AD - NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/08/03/ PY - 2001 DA - 2001 Aug 03 SP - 28991 EP - 28998 VL - 276 IS - 31 SN - 0021-9258, 0021-9258 KW - Amides KW - 0 KW - Furocoumarins KW - Indicators and Reagents KW - Oligodeoxyribonucleotides KW - Phosphoric Acids KW - phosphoramidic acid KW - 9Q189608GB KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Drug Stability KW - Exons KW - Nucleic Acid Conformation KW - Binding Sites KW - Base Sequence KW - Genetic Techniques KW - Kinetics KW - Molecular Sequence Data KW - Introns KW - CHO Cells KW - Cricetinae KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Oligodeoxyribonucleotides -- chemistry KW - Oligodeoxyribonucleotides -- pharmacology KW - Oligodeoxyribonucleotides -- chemical synthesis KW - Sequence Deletion KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71049401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Targeted+gene+knockout+by+2%27-O-aminoethyl+modified+triplex+forming+oligonucleotides.&rft.au=Puri%2C+N%3BMajumdar%2C+A%3BCuenoud%2C+B%3BNatt%2C+F%3BMartin%2C+P%3BBoyd%2C+A%3BMiller%2C+P+S%3BSeidman%2C+M+M&rft.aulast=Puri&rft.aufirst=N&rft.date=2001-08-03&rft.volume=276&rft.issue=31&rft.spage=28991&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional Domains of the ClpA and ClpX Molecular Chaperones Identified by Limited Proteolysis and Deletion Analysis AN - 18074816; 5150850 AB - Escherichia coli ClpA and ClpX are ATP-dependent protein unfoldases that each interact with the protease, ClpP, to promote specific protein degradation. We have used limited proteolysis and deletion analysis to probe the conformations of ClpA and ClpX and their interactions with ClpP and substrates. ATP gamma S binding stabilized ClpA and ClpX such that that cleavage by lysylendopeptidase C occurred at only two sites. Both proteins were cleaved within in a loop preceding an alpha -helix-rich C-terminal domain. Although the loop varies in size and composition in Clp ATPases, cleavage occurred within and around a conserved triad, IG(F/L). Binding of ClpP blocked this cleavage, and prior cleavage at this site rendered both ClpA and ClpX defective in binding and activating ClpP, suggesting that this site is involved in interactions with ClpP. ClpA was also cut at a site near the junction of the two ATPase domains, whereas the second cleavage site in ClpX lay between its N- terminal and ATPase domains. ClpP did not block cleavage at these other sites. The N-terminal domain of ClpX dissociated upon cleavage, and the remaining ClpX Delta N remained as a hexamer, associated with ClpP, and expressed ATPase, chaperone, and proteolytic activity. A truncated mutant of ClpA lacking its N-terminal 153 amino acids also formed a hexamer, associated with ClpP, and expressed these activities. We propose that the N-terminal domains of ClpX and ClpA lie on the outside ring surface of the holoenzyme complexes where they contribute to substrate binding or perform a gating function affecting substrate access to other binding sites and that a loop on the opposite face of the ATPase rings stabilizes interactions with ClpP and is involved in promoting ClpP proteolytic activity. JF - Journal of Biological Chemistry AU - Singh, S K AU - Rozycki, J AU - Ortega, J AU - Ishikawa, T AU - Lo, J AU - Steven, A C AU - Maurizi, M R AD - Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2001/08/03/ PY - 2001 DA - 2001 Aug 03 SP - 29420 EP - 29429 VL - 276 IS - 31 SN - 0021-9258, 0021-9258 KW - ClpA protein KW - ClpX protein KW - Microbiology Abstracts B: Bacteriology KW - Proteolysis KW - Escherichia coli KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18074816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Functional+Domains+of+the+ClpA+and+ClpX+Molecular+Chaperones+Identified+by+Limited+Proteolysis+and+Deletion+Analysis&rft.au=Singh%2C+S+K%3BRozycki%2C+J%3BOrtega%2C+J%3BIshikawa%2C+T%3BLo%2C+J%3BSteven%2C+A+C%3BMaurizi%2C+M+R&rft.aulast=Singh&rft.aufirst=S&rft.date=2001-08-03&rft.volume=276&rft.issue=31&rft.spage=29420&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Proteolysis ER - TY - JOUR T1 - Conditional Coupling of Leading-strand and Lagging-strand DNA Synthesis at Bacteriophage T4 Replication Forks AN - 17905562; 5150834 AB - Eight proteins encoded by bacteriophage T4 are required for the replicative synthesis of the leading and lagging strands of T4 DNA. We show here that active T4 replication forks, which catalyze the coordinated synthesis of leading and lagging strands, remain stable in the face of dilution provided that the gp44/62 clamp loader, the gp45 sliding clamp, and the gp32 ssDNA-binding protein are present at sufficient levels after dilution. If any of these accessory proteins is omitted from the dilution mixture, uncoordinated DNA synthesis occurs, and/or large Okazaki fragments are formed. Thus, the accessory proteins must be recruited from solution for each round of initiation of lagging-strand synthesis. A modified bacteriophage T7 DNA polymerase (Sequenase) can replace the T4 DNA polymerase for leading-strand synthesis but not for well coordinated lagging-strand synthesis. Although T4 DNA polymerase has been reported to self-associate, gel-exclusion chromatography displays it as a monomer in solution in the absence of DNA. It forms no stable holoenzyme complex in solution with the accessory proteins or with the gp41-gp61 helicase-primase. Instead, template DNA is required for the assembly of the T4 replication complex, which then catalyzes coordinated synthesis of leading and lagging strands in a conditionally coupled manner. JF - Journal of Biological Chemistry AU - Kadyrov, F A AU - Drake, J W AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA, kadyrov@niehs.nih.gov Y1 - 2001/08/03/ PY - 2001 DA - 2001 Aug 03 SP - 29559 EP - 29566 VL - 276 IS - 31 SN - 0021-9258, 0021-9258 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Lag phase KW - DNA biosynthesis KW - Replication KW - Phage T4 KW - Okazaki fragments KW - Leader sequence KW - DNA-directed DNA polymerase KW - DNA KW - N 14651:Virus & phage infections KW - J 02750:Phage-host interactions KW - V 22031:Viral nucleic acids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Conditional+Coupling+of+Leading-strand+and+Lagging-strand+DNA+Synthesis+at+Bacteriophage+T4+Replication+Forks&rft.au=Kadyrov%2C+F+A%3BDrake%2C+J+W&rft.aulast=Kadyrov&rft.aufirst=F&rft.date=2001-08-03&rft.volume=276&rft.issue=31&rft.spage=29559&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage T4; DNA-directed DNA polymerase; Replication; DNA biosynthesis; Leader sequence; Lag phase; Okazaki fragments; DNA ER - TY - JOUR T1 - A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families AN - 899129755; 13758504 AB - One of the most common melanoma-related CDKN2A mutations reported in North America is the V126D mutation. We examined nine markers surrounding CDKN2A in three American and four Canadian families carrying the V126D mutation. All seven families had a haplotype consistent with a common ancestor/founder for this mutation. In addition, the mutation appears to have originated 34-52 generations ago (1-LOD-unit support interval 13-98 generations). http:///www.bjcancer.com [copy 2001 Cancer Research Campaign JF - British Journal of Cancer AU - Goldstein, A M AU - Liu, L AU - Shennan, M G AU - Hogg, D AU - Tucker, M A AU - Struewing, J P AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, 20892, USA; Departments of Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 527 EP - 530 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 85 IS - 4 SN - 0007-0920, 0007-0920 KW - Genetics Abstracts; Toxicology Abstracts KW - Haplotypes KW - Mutation KW - Cancer KW - G 07880:Human Genetics KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/899129755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=A+common+founder+for+the+V126D+CDKN2A+mutation+in+seven+North+American+melanoma-prone+families&rft.au=Goldstein%2C+A+M%3BLiu%2C+L%3BShennan%2C+M+G%3BHogg%2C+D%3BTucker%2C+M+A%3BStruewing%2C+J+P&rft.aulast=Goldstein&rft.aufirst=A&rft.date=2001-08-01&rft.volume=85&rft.issue=4&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1054%2Fbjoc.2001.1944 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-10-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Haplotypes; Mutation; Cancer DO - http://dx.doi.org/10.1054/bjoc.2001.1944 ER - TY - JOUR T1 - Ischemic colitis associated with paclitaxel. AN - 85354322; pmid-11468447 AB - Systemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. This report describes the case of a 49-year-old woman with liver metastases from a neuroendocrine tumor of unknown origin who developed mild ischemic colitis after chemotherapy with carboplatin and paclitaxel. The patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea, which resolved in about 10 days. She had a normal white blood cell count throughout her illness; the assay of stool specimens for Clostridium difficile toxins and the stool cultures were both negative. A sigmoidoscopy showed a mild, transient ischemic colitis, which was confirmed by pathologic examination of the biopsy specimens. Although carboplatin is not related to severe colonic cytotoxicity, it has been previously reported that paclitaxel induces necrosis of the gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is the most frequent complication in patients with cancer who undergo paclitaxel-based chemotherapy and develop gastrointestinal toxicity. Once C. difficile infection has been excluded, a diagnosis of ischemic colitis should be considered, especially in patients with cancer who have normal white blood cell counts. JF - Journal of clinical gastroenterology AU - Daniele, B AU - Rossi, G B AU - Losito, S AU - Gridelli, C AU - de Bellis, M AD - Department of Medical Oncology, National Cancer Institute and G. Pascale Foundation, Naples, Italy. bdaniele@sirio-oncology.it Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 159 EP - 160 VL - 33 IS - 2 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - *Antineoplastic Combined Chemotherapy Protocols: adverse effects KW - Antineoplastic Combined Chemotherapy Protocols: therapeutic use KW - Biopsy KW - Carboplatin: administration & dosage KW - Carboplatin: adverse effects KW - *Colitis, Ischemic: chemically induced KW - Colitis, Ischemic: pathology KW - Diagnosis, Differential KW - Female KW - Humans KW - Intestinal Mucosa: pathology KW - Liver Neoplasms: drug therapy KW - *Liver Neoplasms: secondary KW - Middle Aged KW - *Neoplasms, Unknown Primary: drug therapy KW - Neuroendocrine Tumors: drug therapy KW - *Neuroendocrine Tumors: secondary KW - Paclitaxel: administration & dosage KW - *Paclitaxel: adverse effects KW - Sigmoidoscopy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85354322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Novel+domains+of+the+prokaryotic+two-component+signal+transduction+systems&rft.au=Galperin%2C+MY%3BNikolskaya%2C+AN%3BKoonin%2C+E+V&rft.aulast=Galperin&rft.aufirst=MY&rft.date=2001-09-11&rft.volume=203&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - A novel food-delivery device for neurophysiological and neuropsychological studies in monkeys. AN - 85273570; pmid-11513947 AB - Neurophysiological and neuropsychological studies in monkeys sometimes require an automated food-pellet dispenser. Commercially available dispensers typically sequester the pellet until delivery and, once delivered, the pellet's availability cannot be controlled. The custom-designed dispenser described here overcomes those two limitations. The device is composed of two separate units: a feeder and an electronic controller. The feeder manipulates food pellets with actuators driven by air pressure and delivers them into a serving bowl. The controller's settings determine whether the monkey can retrieve a pellet from the bowl. If the experiment requires that the pellet be visible and within reach, but unavailable for retrieval, the controller enables a trap-door mechanism at the bottom of the bowl. Any motion near the serving bowl, such as that caused by the approach of a monkey's hand, will then trigger the opening of the trap door, which causes the pellet to fall into an enclosed pellet collector. This rapid pellet-removal mechanism can also be triggered by other computer-controlled contingencies. Two of these dispensers have been in operation in an applied laboratory setting for over 2 years. JF - Journal of Neuroscience Methods AU - Mitz, A R AU - Boring, S A AU - Wise, S P AU - Lebedev, M A AD - Laboratory of Systems Neuroscience, National Institute of Mental Health, 49 Convent Drive, Building 49, Room B1EE17, Bethesda, MD 20892-4401, USA. PY - 2001 SP - 129 EP - 135 VL - 109 IS - 2 SN - 0165-0270, 0165-0270 KW - Neuropsychology KW - Animal Feed KW - Learning KW - Food Dispensers, Automatic KW - Conditioning (Psychology) KW - Housing, Animal KW - Animal KW - Algorithms KW - Feeding Behavior KW - Neurophysiology KW - Haplorhini KW - Feeding Methods KW - Behavior, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neuroscience+Methods&rft.atitle=A+novel+food-delivery+device+for+neurophysiological+and+neuropsychological+studies+in+monkeys.&rft.au=Mitz%2C+A+R%3BBoring%2C+S+A%3BWise%2C+S+P%3BLebedev%2C+M+A&rft.aulast=Mitz&rft.aufirst=A&rft.date=2001-08-01&rft.volume=109&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroscience+Methods&rft.issn=01650270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections. AN - 72387229; 11772269 AB - Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-beta-D-glucan. This homopolysaccharide is a major component of the cell wall of many pathogenic fungi and yet is absent in mammalian cells. It provides osmotic stability and is important for cell growth and cell division. In vitro, caspofungin has broad-spectrum antifungal activity against Candida and Aspergillus spp. without cross-resistance to existing agents. The compound exerts prolonged post-antifungal effects and fungicidal activity against Candida spp. and causes severe damage of Aspergillus fumigatus at the sites of hyphal growth. Animal models have demonstrated efficacy against disseminated candidiasis and disseminated and pulmonary aspergillosis, both in normal and in immunocompromised animals. Caspofungin possesses favourable pharmacokinetic properties and is not metabolised through the cytochrome P450 (CYP) enzyme system. It showed highly promising antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oesophageal candidiasis. Caspofungin was effective in patients with invasive aspergillosis intolerant or refractory to standard therapies. Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients. JF - Expert opinion on investigational drugs AU - Groll, A H AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Rm. 13 N240, 10 Center Drive, Bethesda, MD 20892, USA. grolla@mail.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 1545 EP - 1558 VL - 10 IS - 8 SN - 1354-3784, 1354-3784 KW - Anti-Bacterial Agents KW - 0 KW - Antifungal Agents KW - Echinocandins KW - Lipopeptides KW - Peptides KW - Peptides, Cyclic KW - caspofungin KW - F0XDI6ZL63 KW - Index Medicus KW - Animals KW - Humans KW - Female KW - Pregnancy KW - Anti-Bacterial Agents -- therapeutic use KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacokinetics KW - Anti-Bacterial Agents -- adverse effects KW - Anti-Bacterial Agents -- pharmacology KW - Anti-Bacterial Agents -- pharmacokinetics KW - Antifungal Agents -- therapeutic use KW - Antifungal Agents -- pharmacology KW - Antifungal Agents -- chemistry KW - Anti-Bacterial Agents -- chemistry KW - Mycoses -- complications KW - Mycoses -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72387229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Caspofungin%3A+pharmacology%2C+safety+and+therapeutic+potential+in+superficial+and+invasive+fungal+infections.&rft.au=Groll%2C+A+H%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=2001-08-01&rft.volume=276&rft.issue=37&rft.spage=34708&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-01 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors affecting R6 fungicide toxicity on sea urchin fertilization and early development: roles of exposure routes and mixture components. AN - 72313773; 11727791 AB - A technical fungicide mixture, R6 and its components, cymoxanil (CYM) and cupric oxychloride (Cu-OCl), were tested by sea urchin bioassays (Paracentrotus lividus and Sphaerechinus granularis). A set of toxicity endpoints was evaluated including both lethal and sublethal effects with the following endpoints: (a) acute embryotoxicity, (b) developmental defects, (c) changes in sperm fertilization success, (d) transmissible damage from sperm to the offspring, and (e) cytogenetic abnormalities. Acute effects on developing embryos were observed as early (prehatch) mortality at R6 levels > or =25 microg/ml. The pesticide mixture R6 was tested at realistic concentrations, ranging from 25 ng/ ml to 2.5 microg/ml, and the two components, CYM and Cu-OCl, were tested, either alone or in mixture, at concentrations equal to their levels in the corresponding R6 solutions. R6 was either dissolved in filtered seawater (water only, W-O), or spiked in "pristine" silt-clay sediment or soil samples before bioassays. Developmental toxicity of R6, following W-O dissolution, displayed a significant dose-related increase of larval malformations and differentiation arrest at concentrations of 750 ng/ml to 2.5 microg/ml both in P. lividus and in S. granularis larvae. Developmental toxicity was removed in spiked sediment up to R6 nominal levels (25 microg/ml), 10-fold above the embryotoxic R6 levels in W-O exposure. No significant developmental toxicity was exerted by CYM or Cu-OCl (W-O exposure) up to their concentrations equivalent to 2.5 microg/ml R6. The laboratory-prepared mixture of CYM and Cu-OCl, in the same concentration range, only resulted in minor effects, as larval retardation, suggesting the presence of toxic impurities (or additional components) in the R6 formulation. When sperm from either P. lividus or S. granularis were exposed to R6 before fertilization, a W-O exposure resulted in a dose-related decrease in fertilization of P. lividus sperm (up to 250 microg/ml R6), whereas S. granularis sperm underwent a significant increase of fertilization rate at the highest R6 nominal levels (up to 25 microg/ml). Equivalent CYM or Cu-OCl levels were ineffective on sperm fertilization success in both species. The offspring of S. granularis sperm exposed to 25 microg/ml R6 showed a significant increase in larval malformations, which were not detected in the offspring of R6-exposed P. lividus sperm. Again, CYM or Cu-OCl was unable to exert any transmissible damage from sperm to the offspring in either species. The present study raises the case of possible discrepancies between toxicity of a technical mixture and of its analytical-grade components, also providing evidence for a loss of pesticide toxicity following dispersion in an environmental matrix such as sediment or soil. JF - Human & experimental toxicology AU - Pagano, G AU - Iaccarino, M AU - De Biase, A AU - Meriç, S G AU - Warnau, M AU - Oral, R AU - Trieff, N M AD - Italian National Cancer Institute, G. Pascale Foundation, Naples, Italy. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 404 EP - 411 VL - 20 IS - 8 SN - 0960-3271, 0960-3271 KW - Acetamides KW - 0 KW - Fungicides, Industrial KW - Soil KW - 2-cyano-N-((ethylamino)carbonyl)-2-(methoxyimino)acetamide KW - 57966-95-7 KW - copper oxychloride KW - 76712031PG KW - Copper KW - 789U1901C5 KW - Index Medicus KW - Animals KW - Geologic Sediments -- analysis KW - Spermatozoa -- drug effects KW - Embryo, Nonmammalian -- abnormalities KW - Toxicity Tests, Acute KW - Environmental Exposure KW - Soil -- analysis KW - Fertilization -- drug effects KW - Embryo, Nonmammalian -- drug effects KW - Spermatozoa -- abnormalities KW - Male KW - Female KW - Sea Urchins -- drug effects KW - Acetamides -- toxicity KW - Sea Urchins -- embryology KW - Ovum -- drug effects KW - Fungicides, Industrial -- toxicity KW - Copper -- toxicity KW - Sea Urchins -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72313773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=Factors+affecting+R6+fungicide+toxicity+on+sea+urchin+fertilization+and+early+development%3A+roles+of+exposure+routes+and+mixture+components.&rft.au=Pagano%2C+G%3BIaccarino%2C+M%3BDe+Biase%2C+A%3BMeri%C3%A7%2C+S+G%3BWarnau%2C+M%3BOral%2C+R%3BTrieff%2C+N+M&rft.aulast=Pagano&rft.aufirst=G&rft.date=2001-08-01&rft.volume=20&rft.issue=8&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-12 N1 - Date created - 2001-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Approaches to interrupting HAART for the treatment of HIV infection. IAPAC sessions 2001, July 18-19, 2001 - Chicago. AN - 72244332; 11708275 JF - IAPAC monthly AU - Dybul, M AU - National Institute of Allergy and Infectious Disease, US National Institutes of Health, USA Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 232 EP - 234 VL - 7 IS - 8 KW - AIDS/HIV KW - Viral Load KW - Drug Administration Schedule KW - Drug Resistance, Viral KW - Patient Compliance KW - Humans KW - Treatment Outcome KW - CD4 Lymphocyte Count KW - Time Factors KW - Research Design KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - HIV Infections -- virology KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Antiretroviral Therapy, Highly Active -- psychology KW - Antiretroviral Therapy, Highly Active -- economics KW - Antiretroviral Therapy, Highly Active -- methods KW - Salvage Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72244332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=IAPAC+monthly&rft.atitle=Approaches+to+interrupting+HAART+for+the+treatment+of+HIV+infection.+IAPAC+sessions+2001%2C+July+18-19%2C+2001+-+Chicago.&rft.au=Dybul%2C+M%3BNational+Institute+of+Allergy+and+Infectious+Disease%2C+US+National+Institutes+of+Health%2C+USA&rft.aulast=Dybul&rft.aufirst=M&rft.date=2001-08-01&rft.volume=7&rft.issue=8&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=IAPAC+monthly&rft.issn=15451089&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer. AN - 72240243; 11685731 AB - New therapeutic alternatives are needed to improve outcomes in patients with androgen-independent prostate cancer (AIPC). For several years, researchers at the National Cancer Institute have been interested in elucidating the importance of angiogenesis in the pathogenesis of prostate cancer and in identifying inhibitors of this process. Thalidomide has been shown to inhibit the ability of tumors to recruit new blood vessels. In a recent phase II trial of thalidomide in AIPC, 28% of patients achieved a prostate-specific antigen (PSA) decrease of >40%. The taxane docetaxel also produces PSA and measurable disease responses when used as monotherapy or as a component of combination chemotherapy for AIPC. Thus, based on the single-agent activity of thalidomide and docetaxel, we initiated a randomized phase II study of weekly docetaxel with or without thalidomide, 200 mg at bedtime, in patients with chemotherapy-naive metastatic AIPC. Docetaxel, 30 mg/m(2) intravenously, was administered every 7 days for 3 weeks, followed by a 1-week rest period. Both regimens have been well tolerated among the first 59 treated patients, with a near absence of grade (3/4) myelosuppression. Fatigue, hyperglycemia, and pulmonary toxicity were seen in both groups. Thrombotic events have been seen in the combination arm. Thirty-five percent (6 of 17) of the patients receiving docetaxel alone and 53% (19 of 36) of those receiving docetaxel and thalidomide have had a PSA decrease of at least 50%. Combining a cytotoxic agent with an angiogenesis inhibitor is a promising area of investigation for prostate cancer management. Copyright 2001 by W.B. Saunders Company. JF - Seminars in oncology AU - Figg, W D AU - Arlen, P AU - Gulley, J AU - Fernandez, P AU - Noone, M AU - Fedenko, K AU - Hamilton, M AU - Parker, C AU - Kruger, E A AU - Pluda, J AU - Dahut, W L AD - Medicine Branch, Division of Clinical Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 62 EP - 66 VL - 28 IS - 4 Suppl 15 SN - 0093-7754, 0093-7754 KW - Angiogenesis Inhibitors KW - 0 KW - Antineoplastic Agents KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Thalidomide KW - 4Z8R6ORS6L KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Angiogenesis Inhibitors -- therapeutic use KW - Prostatic Neoplasms -- pathology KW - Paclitaxel -- analogs & derivatives KW - Adenocarcinoma -- secondary KW - Paclitaxel -- therapeutic use KW - Thalidomide -- therapeutic use KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72240243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=A+randomized+phase+II+trial+of+docetaxel+%28taxotere%29+plus+thalidomide+in+androgen-independent+prostate+cancer.&rft.au=Figg%2C+W+D%3BArlen%2C+P%3BGulley%2C+J%3BFernandez%2C+P%3BNoone%2C+M%3BFedenko%2C+K%3BHamilton%2C+M%3BParker%2C+C%3BKruger%2C+E+A%3BPluda%2C+J%3BDahut%2C+W+L&rft.aulast=Figg&rft.aufirst=W&rft.date=2001-08-01&rft.volume=28&rft.issue=4+Suppl+15&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signal transduction events in mammalian cells in response to ionizing radiation. AN - 71317426; 12018572 AB - Ionizing radiations elicit a variety of biological effects in mammalian cells. In recent years altered signal transduction has been recognized as a key cellular response to ionizing radiation. Several oncogenes, the products of which are components of signal transduction pathways and which are over-expressed in many tumors, are specifically induced in cells exposed to radiation. It has also become evident that the oncogene ras and the serine/threonine protein kinase oncogenes raf and PKC confer radio-resistance to tumor cells. Modulation of these genes or their activity by natural compounds may offer a strategy to treat cancer by enhancing radiation-induced apoptosis of tumor cells. JF - Indian journal of experimental biology AU - Bhattacharya, R K AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, India. cncinst@giasc101.vsnl.net.in Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 727 EP - 734 VL - 39 IS - 8 SN - 0019-5189, 0019-5189 KW - Index Medicus KW - Animals KW - Oncogenes KW - Apoptosis KW - Mammals KW - Humans KW - Radiation Tolerance KW - Proto-Oncogenes KW - Signal Transduction -- genetics KW - Signal Transduction -- radiation effects KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71317426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=From+carcinogenesis+to+clinical+interventions+for+cancer+prevention&rft.au=Greenwald%2C+P&rft.aulast=Greenwald&rft.aufirst=P&rft.date=2001-09-14&rft.volume=166&rft.issue=1-2&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-13 N1 - Date created - 2002-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of experimental mucosal inflammation. AN - 71193824; 11570528 AB - Studies conducted over the past 10 years have provided ample evidence that many types of inflammations arising from basic abnormalities of immune regulation are ultimately 'funneled' through a Th1 or Th2 T cell-mediated immune reaction. Thus, by understanding these types of reactions and, in particular, by identifying their natural checkpoints, one can control the inflammation regardless of its more basic causes. A case in point is the inflammatory disease of the intestine known as Crohn disease, a disease now thought to be due to one or more abnormalities leading to an excessive immune response to elements of the bacterial microflora of the gut. Both in murine models and by study of Crohn disease itself, we have shown that Crohn inflammation is due to a Th1 T-cell abnormality involving overproduction of interleukin (IL)-12, interferon (IFN-gamma, and tumor necrosis factor (TNF)-alpha. In addition, we and others have shown that treatment of mice with anti-IL-12 or other agents that downregulate the level of IL- 12 secretion can have a dramatic effect on the inflammation. This is because anti-IL-12 administration leads to apoptosis of activated Th1 T cells. A second checkpoint of Th1 T-cell-mediated inflammation involves its downregulation by the suppressor cytokine, transforming growth factor (TGF)-beta. We have been delivering TGF-beta to mice with experimental intestinal inflammation, using several novel approaches. In particular, we have successfully treated such mice with intranasally administered DNA encoding active TGF-beta. Another approach currently under investigation is delivery of TGF-beta by gene therapy. These and other developments in the understanding of inflammation paint a bright future for cytokine-based therapeutic agents. It is now apparent that these therapies are not only effective and safe but also potentially long-lasting. JF - Acta odontologica Scandinavica AU - Strober, W AU - Fuss, I AU - Kitani, A AD - Mucosal Immunity Section, Laboratory of Clinical Investigation, NIAID, National Institute of Health, Bethesda, Maryland 20892-1890, USA. wstrober@niaid.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 244 EP - 247 VL - 59 IS - 4 SN - 0001-6357, 0001-6357 KW - Transforming Growth Factor beta KW - 0 KW - Tumor Necrosis Factor-alpha KW - Interleukin-10 KW - 130068-27-8 KW - Interleukin-12 KW - 187348-17-0 KW - Trinitrobenzenesulfonic Acid KW - 8T3HQG2ZC4 KW - Dentistry KW - Index Medicus KW - Animals KW - Th1 Cells -- immunology KW - Gene Transfer Techniques KW - Intestinal Mucosa -- immunology KW - Interleukin-10 -- therapeutic use KW - Mice KW - Interleukin-12 -- antagonists & inhibitors KW - Mice, Inbred Strains KW - Down-Regulation KW - T-Lymphocyte Subsets -- immunology KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- therapeutic use KW - Colitis -- immunology KW - Colitis -- therapy KW - Colitis -- chemically induced KW - Immunotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71193824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+odontologica+Scandinavica&rft.atitle=Regulation+of+experimental+mucosal+inflammation.&rft.au=Strober%2C+W%3BFuss%2C+I%3BKitani%2C+A&rft.aulast=Strober&rft.aufirst=W&rft.date=2001-08-01&rft.volume=59&rft.issue=4&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Acta+odontologica+Scandinavica&rft.issn=00016357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of physical interventions on house dust mite allergen levels in carpet, bed, and upholstery dust in low-income, urban homes. AN - 71184039; 11564617 AB - House dust mite allergen exposure is a postulated risk factor for allergic sensitization, asthma development, and asthma morbidity; however, practical and effective methods to mitigate these allergens from low-income, urban home environments remain elusive. The purpose of this study was to assess the feasibility and effectiveness of physical interventions to mitigate house dust mite allergens in this setting. Homes with high levels of house dust mite allergen (Der f 1 + Der p 1 > or = 10 microg/g dust by enzyme-linked immunosorbent assay) in the bed, bedroom carpet, and/or upholstered furniture were enrolled in the study. Carpets and upholstered furniture were subjected to a single treatment of either dry steam cleaning plus vacuuming (carpet only) or intensive vacuuming alone. Bed interventions consisted of complete encasement of the mattress, box spring, and pillows plus either weekly professional or in-home laundering of nonencased bedding. Dust samples were collected at baseline and again at 3 days (carpet and upholstery only) and 2, 4, and 8 weeks posttreatment. We compared pretreatment mean allergen concentrations and loads to posttreatment values and performed between-group analyses after adjusting for differences in the pretreatment means. Both dry steam cleaning plus vacuuming and vacuuming alone resulted in a significant reduction in carpet house dust mite allergen concentration and load (p < 0.05). Levels approached pretreatment values by 4 weeks posttreatment in the intensive vacuuming group, whereas steam cleaning plus vacuuming effected a decrease that persisted for up to 8 weeks. Significant decreases in bed house dust mite allergen concentration and load were obtained in response to encasement and either professional or in-home laundering (p < 0.001). Between-group analysis revealed significantly less postintervention house dust mite allergen load in professionally laundered compared to home-laundered beds (p < 0.05). Intensive vacuuming and dry steam cleaning both caused a significant reduction in allergen concentration and load in upholstered furniture samples (p < 0.005). Based on these data, we conclude that physical interventions offer practical, effective means of reducing house dust mite allergen levels in low-income, urban home environments. JF - Environmental health perspectives AU - Vojta, P J AU - Randels, S P AU - Stout, J AU - Muilenberg, M AU - Burge, H A AU - Lynn, H AU - Mitchell, H AU - O'Connor, G T AU - Zeldin, D C AD - Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 815 EP - 819 VL - 109 IS - 8 SN - 0091-6765, 0091-6765 KW - Allergens KW - 0 KW - Dust KW - Index Medicus KW - Animals KW - Floors and Floorcoverings KW - Washington KW - Interior Design and Furnishings KW - Poverty KW - Humans KW - Housekeeping -- methods KW - Laundering -- methods KW - Bedding and Linens KW - Urban Population KW - Housing KW - Dust -- analysis KW - Mites -- immunology KW - Hypersensitivity -- prevention & control KW - Environmental Exposure -- prevention & control KW - Dust -- adverse effects KW - Allergens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71184039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Effects+of+physical+interventions+on+house+dust+mite+allergen+levels+in+carpet%2C+bed%2C+and+upholstery+dust+in+low-income%2C+urban+homes.&rft.au=Vojta%2C+P+J%3BRandels%2C+S+P%3BStout%2C+J%3BMuilenberg%2C+M%3BBurge%2C+H+A%3BLynn%2C+H%3BMitchell%2C+H%3BO%27Connor%2C+G+T%3BZeldin%2C+D+C&rft.aulast=Vojta&rft.aufirst=P&rft.date=2001-08-01&rft.volume=109&rft.issue=8&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-25 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1998 Oct;106(10):659-64 [9755142] Thorax. 1998 Jan;53(1):63-72 [9577525] J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):203-5 [10075519] Lancet. 2000 Oct 21;356(9239):1392-7 [11052581] Lancet. 1982 Sep 25;2(8300):675-8 [6126624] Pediatrics. 1983 Mar;71(3):418-22 [6338475] Q J Med. 1986 Feb;58(226):199-215 [3520626] J Allergy Clin Immunol. 1987 May;79(5):781-91 [3571770] J Allergy Clin Immunol. 1987 Aug;80(2):184-94 [3611539] Thorax. 1988 Feb;43(2):98-102 [3353895] Exp Appl Acarol. 1988 Feb;4(1):53-62 [3378462] Lancet. 1990 Feb 17;335(8686):396-7 [1968126] N Engl J Med. 1990 Aug 23;323(8):502-7 [2377175] J Allergy Clin Immunol. 1992 May;89(5):1046-60 [1349902] Lancet. 1992 Jun 20;339(8808):1493-7 [1351183] J Allergy Clin Immunol. 1992 Jul;90(1):135-8 [1629503] J Allergy Clin Immunol. 1992 Oct;90(4 Pt 1):599-608 [1401643] Lancet. 1993 Jul 10;342(8863):126 [8100902] Pediatr Allergy Immunol. 1993 Aug;4(3):136-43 [8220802] J Allergy Clin Immunol. 1994 May;93(5):842-6 [8182225] Am J Respir Crit Care Med. 1995 Jun;151(6):1786-93 [7767521] J Allergy Clin Immunol. 1995 Sep;96(3):325-33 [7560634] Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1805-11 [8520740] Clin Exp Allergy. 1995 Nov;25(11):1061-6 [8581838] J Allergy Clin Immunol. 1996 Jul;98(1):64-72 [8765819] BMJ. 1996 Oct 12;313(7062):916 [8876094] N Engl J Med. 1997 May 8;336(19):1356-63 [9134876] Pediatr Pulmonol. 1997 Oct;24(4):237-52 [9368258] N Z Med J. 1997 Nov 28;110(1056):438-9 [9418840] J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):179-91 [9949306] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IFN-gamma is effective in reducing infections in the mouse model of chronic granulomatous disease (CGD). AN - 71175122; 11559434 AB - Chronic granulomatous disease (CGD) is a genetic disorder characterized by recurrent bacterial and fungal infections and tissue granuloma formation. CGD phagocytes are unable to generate superoxide because of mutations in any of four proteins of the phagocyte NADPH oxidase. Prophylactic recombinant human interferon-gamma (IFN-gamma) has been shown to reduce the frequency and severity of infections in CGD patients, but its mechanism(s) remains undefined, and its benefit has been questioned. We investigated the prophylactic effect of IFN-gamma in the mouse model of the major autosomal recessive (p47(phox)) form of CGD. In a prospective, randomized, placebo-controlled study, we compared IFN-gamma, 20,000 U administered subcutaneously (s.c.) three times weekly, to placebo in 118 p47(phox-/-) mice. By 6 weeks of study, there were 3 infections in the IFN-gamma group compared with 13 infections in the placebo group (77% reduction in infections, p<0.01). By 18 months of study, there were 7 infections in the IFN-gamma group compared with 18 infections in the placebo group (39% reduction in infections, p<0.01). Two animals receiving IFN-gamma had seizures after 7 months in the study. No other toxicities were observed. Peripheral blood phagocytes from IFN-gamma treated p47(phox-/-) mice produced no superoxide, excluding restoration of the oxidative burst as a mechanism for the IFN-gamma effect. There were no differences in either peritoneal macrophage nitrate production or thioglycollate-induced peritoneal exudate between treatment groups. This animal model demonstrates a prophylactic benefit of IFN-gamma similar to that seen in humans and provides an opportunity to investigate the mechanism(s) of action for IFN-gamma in CGD. JF - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research AU - Jackson, S H AU - Miller, G F AU - Segal, B H AU - Mardiney, M AU - Domachowske, J B AU - Gallin, J I AU - Holland, S M AD - The Laboratory of Host Defenses, NIAID, NIH, Bethesda, MD 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 567 EP - 573 VL - 21 IS - 8 SN - 1079-9907, 1079-9907 KW - Phosphoproteins KW - 0 KW - Recombinant Proteins KW - Thioglycolates KW - Interferon-gamma KW - 82115-62-6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Index Medicus KW - Animals KW - Phosphoproteins -- genetics KW - Thioglycolates -- administration & dosage KW - Random Allocation KW - Mice KW - Peritonitis -- genetics KW - Peritonitis -- prevention & control KW - Mice, Knockout KW - Phosphoproteins -- deficiency KW - Peritonitis -- enzymology KW - Prospective Studies KW - Nitric Oxide Synthase -- genetics KW - Respiratory Burst -- genetics KW - Mice, Inbred C57BL KW - Nitric Oxide Synthase -- metabolism KW - Drug Evaluation, Preclinical KW - Macrophages, Peritoneal -- enzymology KW - Skin Diseases, Infectious -- enzymology KW - Granulomatous Disease, Chronic -- enzymology KW - Interferon-gamma -- therapeutic use KW - Abscess -- prevention & control KW - Abscess -- genetics KW - Granulomatous Disease, Chronic -- pathology KW - Disease Models, Animal KW - Abscess -- enzymology KW - Skin Diseases, Infectious -- genetics KW - Granulomatous Disease, Chronic -- genetics KW - Granulomatous Disease, Chronic -- microbiology KW - Skin Diseases, Infectious -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71175122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.atitle=IFN-gamma+is+effective+in+reducing+infections+in+the+mouse+model+of+chronic+granulomatous+disease+%28CGD%29.&rft.au=Jackson%2C+S+H%3BMiller%2C+G+F%3BSegal%2C+B+H%3BMardiney%2C+M%3BDomachowske%2C+J+B%3BGallin%2C+J+I%3BHolland%2C+S+M&rft.aulast=Jackson&rft.aufirst=S&rft.date=2001-08-01&rft.volume=21&rft.issue=8&rft.spage=567&rft.isbn=&rft.btitle=&rft.title=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.issn=10799907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Confusion and dysphoria with low-dose topiramate in a patient with bipolar disorder. AN - 71165919; 11552960 AB - Topiramate, a newer antiepileptic agent, may benefit several neurological and psychiatric states, including bipolar disorder. A physically healthy, stockily built, 47-year-old, hypomanic Asian male with a >20-year history of uneventful use of psychotropic agents received topiramate in a dose that was stepped up to 100 mg/day across 10 days. He developed dysphoria, confusion, word-finding difficulties, and difficulties in maintaining a train of thought; the symptoms vanished within a week of drug discontinuation, and reappeared 1-2 days after rechallenge at a dose of 25 mg/day. It appears that, while confusion is usually a dose-dependent adverse effect of topiramate, certain patients may idiosyncratically develop this adverse effect at very low doses. JF - Bipolar disorders AU - Andrade, C AD - Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. andrade@nimhans.kar.nic.in Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 211 EP - 212 VL - 3 IS - 4 SN - 1398-5647, 1398-5647 KW - Anticonvulsants KW - 0 KW - topiramate KW - 0H73WJJ391 KW - Fructose KW - 30237-26-4 KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Middle Aged KW - Male KW - Fructose -- analogs & derivatives KW - Psychoses, Substance-Induced -- diagnosis KW - Confusion -- diagnosis KW - Fructose -- adverse effects KW - Bipolar Disorder -- drug therapy KW - Anticonvulsants -- adverse effects KW - Fructose -- administration & dosage KW - Anticonvulsants -- administration & dosage KW - Psychoses, Substance-Induced -- etiology KW - Confusion -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71165919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bipolar+disorders&rft.atitle=Confusion+and+dysphoria+with+low-dose+topiramate+in+a+patient+with+bipolar+disorder.&rft.au=Andrade%2C+C&rft.aulast=Andrade&rft.aufirst=C&rft.date=2001-08-01&rft.volume=3&rft.issue=4&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Bipolar+disorders&rft.issn=13985647&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Shaping cocaine abstinence by successive approximation. AN - 71165093; 11550730 AB - Cocaine-using methadone-maintenance patients were randomized to standard contingency management (abstinence group, n = 49) or to a contingency designed to increase contact with reinforcers (shaping group, n = 46). For 8 weeks, both groups earned escalating-value vouchers based on thrice-weekly urinalyses: The abstinence group earned vouchers for cocaine-negative urines only; the shaping group earned vouchers for each urine specimen with a 25% or more decrease in cocaine metabolite (first 3 weeks) and then for negative urines only (last 5 weeks). Cocaine use was lower in the shaping group, but only in the last 5 weeks, when the response requirement was identical. Thus, the shaping contingency appeared to better prepare patients for abstinence. A 2nd phase of the study showed that abstinence induced by escalating-value vouchers can be maintained by a nonescalating schedule, suggesting that contingency management can be practical as a maintenance treatment. JF - Journal of consulting and clinical psychology AU - Preston, K L AU - Umbricht, A AU - Wong, C J AU - Epstein, D H AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. kpreston@intra.nida.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 643 EP - 654 VL - 69 IS - 4 SN - 0022-006X, 0022-006X KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Reinforcement Schedule KW - Methadone -- therapeutic use KW - Token Economy KW - Substance Abuse Detection KW - Humans KW - Adult KW - Opioid-Related Disorders -- rehabilitation KW - Middle Aged KW - Male KW - Female KW - Motivation KW - Behavior Therapy KW - Cocaine-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71165093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+consulting+and+clinical+psychology&rft.atitle=Shaping+cocaine+abstinence+by+successive+approximation.&rft.au=Preston%2C+K+L%3BUmbricht%2C+A%3BWong%2C+C+J%3BEpstein%2C+D+H&rft.aulast=Preston&rft.aufirst=K&rft.date=2001-08-01&rft.volume=69&rft.issue=4&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Journal+of+consulting+and+clinical+psychology&rft.issn=0022006X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iron overload, oxidative stress, and axonal dystrophy in brain disorders. AN - 71163420; 11551744 AB - Hallervorden-Spatz syndrome is an autosomal-recessive brain disorder with signs of extrapyramidal dysfunction and mental deterioration, which associate with iron accumulation in globus pallidus and substantia nigra pars reticulata. Studies of oxidant stress in parkinsonian animal models suggest a linkage of iron overload to axonal dystrophy. Redox cycling of iron complexes (i.e., ferrous citrate and hemoglobin) increases hydroxyl radicals, lipid peroxidation, axonal dystrophy, and necrotic or apoptotic cell death. An increase of oxidative stress in the basal ganglia because of redox cycling of iron complexes leads to dopamine overflow and psychomotor dysfunction. Iron overload-induced axonal dystrophy has been demonstrated consistently using in vitro and in vivo models with a prominent feature of lipid peroxidation. This iron-induced oxidative stress is often accentuated by ascorbate and oxidized glutathione, although it is suppressed by the following antioxidants: S-nitrosoglutathione or nitric oxide, MnSOD mimics, manganese, U-78517F, Trolox, and deferoxamine. Preconditioning induction of stress proteins (i.e., hemeoxygenase-1 and neuronal nitric oxide synthase) and hypothermia therapy suppress the generation of toxic reactive oxygen, lipid, and thiol species evoked by bioactive iron complexes in the brain. Finally, combined antioxidative therapeutics and gene induction procedures may prove to be useful for slowing progressive neurodegeneration caused by iron overload in the brain. JF - Pediatric neurology AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1264, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 138 EP - 147 VL - 25 IS - 2 SN - 0887-8994, 0887-8994 KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Child KW - Iron -- metabolism KW - Pantothenate Kinase-Associated Neurodegeneration -- metabolism KW - Iron Overload -- metabolism KW - Oxidative Stress KW - Brain -- metabolism KW - Neuroaxonal Dystrophies -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71163420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+neurology&rft.atitle=Iron+overload%2C+oxidative+stress%2C+and+axonal+dystrophy+in+brain+disorders.&rft.au=Chiueh%2C+C+C&rft.aulast=Chiueh&rft.aufirst=C&rft.date=2001-08-01&rft.volume=25&rft.issue=2&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Pediatric+neurology&rft.issn=08878994&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bidirectional transcriptional activity of PGK-neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice. AN - 71148308; 11536432 AB - In an effort to create a conventional knockout mouse model for multiple endocrine neoplasia type 1 (MEN1), we targeted disruption of the mouse Men1 gene through homologous recombination in ES cells. Men1 exons 2-4 were replaced by a PGK-neomycin cassette inserted in the opposite direction of Men1 transcription (Men1(MSK/+)). Unexpectedly, the Men1 conventional knockout was lethal in heterozygous, chimeric animals. Analysis of embryos revealed late gestational lethality with some embryos showing omphalocele. This was a very surprising phenotype, given that humans and mice that are heterozygotes for loss of function mutations in MEN1 are phenotypically normal except for a risk of endocrine tumors. Northern analysis of Men1(MSK/+) embryonic stem cell RNA revealed the presence of an abundant, novel transcript of 2.1 kb, in addition to the expected wild-type transcripts of 2.7 kb and 3.1 kb. RT-PCR analysis identified this aberrant transcript as arising from the antisense strand of the PGK promoter. We hypothesize that this transcript is producing either a toxic effect at the RNA level, or a dominant negative effect through the production of an amino-terminal truncated protein product. This example serves as a cautionary reminder that mouse knockouts using PGK-neo may sometimes display phenotypes that reflect more than just the loss of function of the targeted gene. JF - Genesis (New York, N.Y. : 2000) AU - Scacheri, P C AU - Crabtree, J S AU - Novotny, E A AU - Garrett-Beal, L AU - Chen, A AU - Edgemon, K A AU - Marx, S J AU - Spiegel, A M AU - Chandrasekharappa, S C AU - Collins, F S AD - National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 259 EP - 263 VL - 30 IS - 4 SN - 1526-954X, 1526-954X KW - MEN1 protein, human KW - 0 KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Neomycin KW - 1404-04-2 KW - Index Medicus KW - Animals KW - Hernia, Umbilical -- genetics KW - Gene Targeting -- methods KW - Chimera -- genetics KW - Genes, Dominant -- genetics KW - Mice KW - Neomycin -- biosynthesis KW - RNA, Messenger -- genetics KW - Precipitin Tests KW - Embryo, Mammalian -- metabolism KW - Gene Deletion KW - Mice, Knockout KW - Phenotype KW - Exons -- genetics KW - Blotting, Western KW - Genes, Reporter -- genetics KW - RNA, Messenger -- metabolism KW - Promoter Regions, Genetic -- genetics KW - Heterozygote KW - Neoplasm Proteins -- genetics KW - Genes, Lethal -- genetics KW - Transcription, Genetic -- genetics KW - Embryo Loss -- genetics KW - Mutagenesis, Insertional -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71148308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.atitle=Bidirectional+transcriptional+activity+of+PGK-neomycin+and+unexpected+embryonic+lethality+in+heterozygote+chimeric+knockout+mice.&rft.au=Scacheri%2C+P+C%3BCrabtree%2C+J+S%3BNovotny%2C+E+A%3BGarrett-Beal%2C+L%3BChen%2C+A%3BEdgemon%2C+K+A%3BMarx%2C+S+J%3BSpiegel%2C+A+M%3BChandrasekharappa%2C+S+C%3BCollins%2C+F+S&rft.aulast=Scacheri&rft.aufirst=P&rft.date=2001-08-01&rft.volume=30&rft.issue=4&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.issn=1526954X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathways for repair of topoisomerase I covalent complexes in Saccharomyces cerevisiae. AN - 71139336; 11532027 AB - The covalent linkage between DNA and the active site tyrosine of topoisomerase I can be stabilized by chemotherapeutic agents, adjacent DNA lesions, or mutational defects in the topoisomerase itself. Following collision with a replication fork, the covalent complex can be converted to a double-strand break. Tdp1, an enzyme that can hydrolyse the bond between topoisomerase I and DNA, is thought to be involved in the repair of these lesions, but little is known about how such repair is accomplished. Reaction kinetics with model substrates reveal that the catalytic efficiency of Saccharomyces cerevisiae Tdp1 is relatively poor when the scissile bond is located in the middle of a duplex, but much better when it is located at the end of a structure. Survival of yeast after induction of a toxic topoisomerase is substantially reduced by inactivation of the TDP1 gene. Comparison of survival of single and double mutants places TDP1 and RAD52 in the same epistasis group but TDP1 and RAD9 in different epistasis groups. In the absence of RAD9, inactivation of TDP1 has a significant effect on the survival of cells following exposure to camptothecin but is without consequence for the survival of agents that do not target topoisomerase I. Tdp1 acts as a specific repair enzyme for topoisomerase I lesions. Rather than working at their earliest occurrence, the enzyme acts after covalent complexes have been converted to DSBs. A second repair pathway also exists that functions independently of Tdp1 but requires RAD9 function to efficiently repair topoisomerase I-linked DSBs. The efficiency of these pathways differs for complexes induced with the chemotherapeutic agent camptothecin vs. those accumulated by mutant forms of topoisomerase I. JF - Genes to cells : devoted to molecular & cellular mechanisms AU - Pouliot, J J AU - Robertson, C A AU - Nash, H A AD - Laboratory of Molecular Biology, National Institute of Mental Health, Building 36, Room 1B08, Bethesda, MD 20892-4034, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 677 EP - 687 VL - 6 IS - 8 SN - 1356-9597, 1356-9597 KW - DNA, Fungal KW - 0 KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - RAD52 protein, S cerevisiae KW - Rad52 DNA Repair and Recombination Protein KW - Saccharomyces cerevisiae Proteins KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - tyrosyl-DNA phosphodiesterase KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Genotype KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Camptothecin -- pharmacology KW - Saccharomyces cerevisiae Proteins -- genetics KW - Kinetics KW - DNA-Binding Proteins -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Substrate Specificity KW - DNA, Fungal -- metabolism KW - DNA, Fungal -- chemistry KW - DNA Replication KW - DNA-Binding Proteins -- metabolism KW - DNA, Fungal -- biosynthesis KW - Catalysis KW - Saccharomyces cerevisiae -- genetics KW - Phosphoric Diester Hydrolases -- genetics KW - DNA Topoisomerases, Type I -- chemistry KW - DNA Repair KW - Saccharomyces cerevisiae -- enzymology KW - Phosphoric Diester Hydrolases -- metabolism KW - Saccharomyces cerevisiae -- drug effects KW - DNA Topoisomerases, Type I -- metabolism KW - Saccharomyces cerevisiae -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71139336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+to+cells+%3A+devoted+to+molecular+%26+cellular+mechanisms&rft.atitle=Pathways+for+repair+of+topoisomerase+I+covalent+complexes+in+Saccharomyces+cerevisiae.&rft.au=Pouliot%2C+J+J%3BRobertson%2C+C+A%3BNash%2C+H+A&rft.aulast=Pouliot&rft.aufirst=J&rft.date=2001-08-01&rft.volume=6&rft.issue=8&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=Genes+to+cells+%3A+devoted+to+molecular+%26+cellular+mechanisms&rft.issn=13569597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-28 N1 - Date created - 2001-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - State-specific trends in smoke-free workplace policy coverage: the current population survey tobacco use supplement, 1993 to 1999. AN - 71122314; 11515250 AB - We examined trends in smoke-free workplace policies among all indoor workers in the United States using the National Cancer Institute's Tobacco Use Supplement to the Census Bureau's Current Population Survey (total n = 270,063). Smoke-free was defined as smoking not permitted in public or common areas or in work areas of a worksite. Nationally, we found that nearly 70% of the US workforce worked under a smoke-free policy in 1999. At the state level, a greater than 30-percentage-point differential existed in the proportion of workers with such policies. Although significant progress has been made to reduce worker exposure to environmental tobacco smoke on the job, we predict further progress may be difficult unless comprehensive regulations to protect all workers are implemented at the national, state, or local level. JF - Journal of occupational and environmental medicine AU - Shopland, D R AU - Gerlach, K K AU - Burns, D M AU - Hartman, A M AU - Gibson, J T AD - Smoking and Tobacco Control Program, National Cancer Institute, Bethesda, Md., USA. reedonald@aol.com Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 680 EP - 686 VL - 43 IS - 8 SN - 1076-2752, 1076-2752 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - United States KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Tobacco Smoke Pollution -- prevention & control KW - Tobacco Smoke Pollution -- legislation & jurisprudence KW - Workplace -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71122314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+and+environmental+medicine&rft.atitle=State-specific+trends+in+smoke-free+workplace+policy+coverage%3A+the+current+population+survey+tobacco+use+supplement%2C+1993+to+1999.&rft.au=Shopland%2C+D+R%3BGerlach%2C+K+K%3BBurns%2C+D+M%3BHartman%2C+A+M%3BGibson%2C+J+T&rft.aulast=Shopland&rft.aufirst=D&rft.date=2001-08-01&rft.volume=43&rft.issue=8&rft.spage=680&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+and+environmental+medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-03 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predicted amino acid sequences for 100 JCV strains. AN - 71122130; 11517413 AB - DNA sequence variation between JCV genotypes is confined largely to noncoding intergenic regions and introns. Nevertheless, evidence suggests that the amino acid sequence variations among the 8 genotypes of JCV can influence the potential for neurovirulence of the virus. In the current study, the amino acid sequences for 100 JCV genomes were translated and grouped into genotype families. Subtype consensus sequences were determined and the type-specific amino acid sequence variants were identified. JF - Journal of neurovirology AU - Cubitt, C L AU - Cui, X AU - Agostini, H T AU - Nerurkar, V R AU - Scheirich, I AU - Yanagihara, R AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 339 EP - 344 VL - 7 IS - 4 SN - 1355-0284, 1355-0284 KW - Antigens, Viral, Tumor KW - 0 KW - Capsid Proteins KW - VP1 protein, polyomavirus KW - Viral Proteins KW - Viral Regulatory and Accessory Proteins KW - agnoprotein, polyomavirus KW - Index Medicus KW - Virulence KW - Viral Proteins -- genetics KW - Genotype KW - Antigens, Viral, Tumor -- genetics KW - Capsid -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - JC Virus -- genetics KW - JC Virus -- classification KW - JC Virus -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71122130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurovirology&rft.atitle=Predicted+amino+acid+sequences+for+100+JCV+strains.&rft.au=Cubitt%2C+C+L%3BCui%2C+X%3BAgostini%2C+H+T%3BNerurkar%2C+V+R%3BScheirich%2C+I%3BYanagihara%2C+R%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Cubitt&rft.aufirst=C&rft.date=2001-08-01&rft.volume=7&rft.issue=4&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurovirology&rft.issn=13550284&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis. AN - 71108973; 11515869 AB - It has previously been demonstrated that 17-allylamino geldanamycin (17-AAG) enhances paclitaxel-mediated cytotoxicity and downregulates vascular endothelial factor expression in non-small cell lung cancer. This project was designed to evaluate the tumoricidal and antiangiogeneic effects of 17-AAG and paclitaxel in H358 non-small cell lung cancer cells grown as xenografts in nude mice. In vitro cytotoxic drug combination effects were evaluated by (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium bromide-based proliferation assays. The combinations of 17-AAG and paclitaxel were administered intraperitoneally in nude mice bearing H358 tumor xenografts. Tumor volumes were measured weekly. Tumor expression of erbB2, vascular endothelial cell growth factor, von Willebrand factor (tumor microvasculature), and activated caspase 3 (apoptosis) were determined by immunohistochemistry. Five- to 22-fold enhancement of paclitaxel cytotoxicity was achieved by paclitaxel + 17-AAG combination that was paralleled with marked induction of apoptosis. This combination treatment profoundly suppressed tumor growth and significantly prolonged survival of mice bearing H358 xenografts. Immunohistochemical staining of tumor tissues indicated profound reduction of vascular endothelial cell growth factor expression associated with reduction of microvasculature in tumors treated with 17-AAG. Apoptotic cells were more abundant in tumors treated with 17-AAG + paclitaxel than in those treated with 17-AAG or paclitaxel alone. Concurrent exposure of H358 cells to 17-AAG and paclitaxel resulted in supraadditive growth inhibition effects in vitro and in vivo. Analysis of molecular markers of tumor tissues indicated that therapeutic drug levels could be achieved with this chemotherapy regimen leading to significant biological responses. Moreover, 17-AAG-mediated suppression of vascular endothelial cell growth factor production by tumor cells may contribute to the antitumor effects of this drug combination in vivo. JF - The Annals of thoracic surgery AU - Nguyen, D M AU - Lorang, D AU - Chen, G A AU - Stewart, J H AU - Tabibi, E AU - Schrump, D S AD - Section of Thoracic Oncology and Surgical Metabolism, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Dao_Nguyen@nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 371 EP - 8; discussion 378-9 VL - 72 IS - 2 SN - 0003-4975, 0003-4975 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzoquinones KW - Benzothiazoles KW - Endothelial Growth Factors KW - Lactams, Macrocyclic KW - Lymphokines KW - Quinones KW - Tyrphostins KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - tyrphostin AG825 KW - Allylamine KW - 48G762T011 KW - Paclitaxel KW - P88XT4IS4D KW - geldanamycin KW - Z3K3VJ16KU KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Nude KW - Lymphokines -- analysis KW - Neovascularization, Pathologic -- pathology KW - Neoplasm Transplantation KW - Drug Therapy, Combination KW - Apoptosis -- drug effects KW - Endothelial Growth Factors -- analysis KW - Tyrphostins -- pharmacology KW - Drug Synergism KW - Carcinoma, Non-Small-Cell Lung -- blood supply KW - Lung Neoplasms -- blood supply KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Antibiotics, Antineoplastic -- pharmacology KW - Allylamine -- pharmacology KW - Paclitaxel -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Quinones -- pharmacology KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71108973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+thoracic+surgery&rft.atitle=Enhancement+of+paclitaxel-mediated+cytotoxicity+in+lung+cancer+cells+by+17-allylamino+geldanamycin%3A+in+vitro+and+in+vivo+analysis.&rft.au=Nguyen%2C+D+M%3BLorang%2C+D%3BChen%2C+G+A%3BStewart%2C+J+H%3BTabibi%2C+E%3BSchrump%2C+D+S&rft.aulast=Nguyen&rft.aufirst=D&rft.date=2001-08-01&rft.volume=72&rft.issue=2&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+thoracic+surgery&rft.issn=00034975&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of a tissue-specific silencer element in the first intron of the human acid maltase gene. AN - 71107772; 11511924 AB - Deficiency of acid maltase (acid alpha-glucosidase), a lysosomal enzyme that degrades glycogen, results in glycogenosis type II, an autosomal recessive disease whose manifestations and severity largely depend on the level of residual enzyme activity. Previous studies have established that there are transcriptional control elements in the first intron; in particular a silencer responsive to Hes-1 and YY1 has been identified in the human hepatoma line, HepG2. This region functions as an enhancer in human fibroblasts. Here we have localized a silencer active in fibroblasts to a nearby 25-bp element in intron 1. This element repressed thymidine kinase promoter activity by about 50% in both orientations in human fibroblasts. This silencer, as with the previous one, is tissue specific since constructs containing this region are inactive in HepG2 cells. Electrophoretic mobility shift assay revealed three proteins specifically binding to the element in fibroblasts, and site-directed mutagenesis analysis indicated that all the three proteins binding to the element contribute to the silencer function. The data may be helpful for designing therapy to increase the level of enzyme, particularly when, as in most adults with the disease, there is reduced production of structurally normal enzyme. JF - Human genetics AU - Yan, B AU - Raben, N AU - Lu, N AU - Plotz, P H AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 186 EP - 190 VL - 109 IS - 2 SN - 0340-6717, 0340-6717 KW - DNA Primers KW - 0 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - alpha-Glucosidases KW - EC 3.2.1.20 KW - Glucan 1,4-alpha-Glucosidase KW - EC 3.2.1.3 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Introns KW - Enzyme-Linked Immunosorbent Assay KW - Plasmids KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Mutation KW - Fibroblasts -- metabolism KW - Sequence Deletion KW - DNA Primers -- chemistry KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Gene Silencing KW - Glycogen Storage Disease Type II -- genetics KW - Glucan 1,4-alpha-Glucosidase -- metabolism KW - Glucan 1,4-alpha-Glucosidase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71107772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+genetics&rft.atitle=Identification+and+characterization+of+a+tissue-specific+silencer+element+in+the+first+intron+of+the+human+acid+maltase+gene.&rft.au=Yan%2C+B%3BRaben%2C+N%3BLu%2C+N%3BPlotz%2C+P+H&rft.aulast=Yan&rft.aufirst=B&rft.date=2001-08-01&rft.volume=109&rft.issue=2&rft.spage=186&rft.isbn=&rft.btitle=&rft.title=Human+genetics&rft.issn=03406717&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses. . AN - 71098999; 11504272 AB - Acetaminophen-protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen-induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen-protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time of routine blood sampling for clinical monitoring. Six subjects developed "severe" hepatotoxicity (transaminase elevation > 1,000 IU/L), and 6 subjects had transaminase elevation of 100 to 1,000 IU/L. Acetaminophen-protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6,000 IU/L) and high risk for the development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen-protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury. JF - Journal of clinical pharmacology AU - James, L P AU - Farrar, H C AU - Sullivan, J E AU - Givens, T G AU - Kearns, G L AU - Wasserman, G S AU - Walson, P D AU - Hinson, J A AU - Pumford, N R AU - Pediatric Pharmacology Research Unit Network, NICHD AD - Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock 72202, USA. ; Pediatric Pharmacology Research Unit Network, NICHD Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 846 EP - 851 VL - 41 IS - 8 SN - 0091-2700, 0091-2700 KW - Analgesics, Non-Narcotic KW - 0 KW - Proteins KW - Acetaminophen KW - 362O9ITL9D KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Infant KW - Aspartate Aminotransferases -- blood KW - Alanine Transaminase -- blood KW - Liver -- drug effects KW - Humans KW - Drug Overdose KW - Infant, Newborn KW - Child KW - Adolescent KW - Child, Preschool KW - Acetaminophen -- poisoning KW - Acetaminophen -- metabolism KW - Proteins -- metabolism KW - Analgesics, Non-Narcotic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71098999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=Measurement+of+acetaminophen-protein+adducts+in+children+and+adolescents+with+acetaminophen+overdoses.+.&rft.au=James%2C+L+P%3BFarrar%2C+H+C%3BSullivan%2C+J+E%3BGivens%2C+T+G%3BKearns%2C+G+L%3BWasserman%2C+G+S%3BWalson%2C+P+D%3BHinson%2C+J+A%3BPumford%2C+N+R%3BPediatric+Pharmacology+Research+Unit+Network%2C+NICHD&rft.aulast=James&rft.aufirst=L&rft.date=2001-08-01&rft.volume=41&rft.issue=8&rft.spage=846&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-13 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of biomarkers in alcoholism medication trials. AN - 71096186; 11505042 AB - Increasingly, biomarkers are being incorporated into the research design of clinical trials on medications to reduce drinking in alcoholics. To date, however, there has been little analysis of the unique roles that biomarkers can play in such investigations or of the practical and conceptual considerations that surround their best use in this context. Clinical trials of alcoholism medications published between 1985 and the present were abstracted to determine how biomarkers were used and how changes in them related to self-report measures of drinking. Six uses of biomarkers were identified: determination of subjects to be included or excluded in the trial; description of baseline sample characteristics; primary and secondary outcome assessment; corroboration of self-reports of drinking status; specification of patients likely to respond to the medication; and evaluation of drug safety. Use of biomarkers in such studies appears warranted, particularly as an objective source of information on treatment efficacy that can be considered with patient self-report measures of drinking status. Biomarkers related to liver functioning also can assist in determination of drug safety for medications metabolized by the liver. JF - Alcoholism, clinical and experimental research AU - Allen, J P AU - Litten, R Z AU - Strid, N AU - Sillanaukee, P AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20852-7003, USA. jpallenphd@cs.com Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 1119 EP - 1125 VL - 25 IS - 8 SN - 0145-6008, 0145-6008 KW - Biomarkers KW - 0 KW - Transferrin KW - carbohydrate-deficient transferrin KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Index Medicus KW - Transferrin -- analogs & derivatives KW - Sensitivity and Specificity KW - Humans KW - Clinical Trials as Topic KW - gamma-Glutamyltransferase -- blood KW - Transferrin -- analysis KW - Research KW - Male KW - Female KW - Biomarkers -- blood KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71096186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=The+role+of+biomarkers+in+alcoholism+medication+trials.&rft.au=Allen%2C+J+P%3BLitten%2C+R+Z%3BStrid%2C+N%3BSillanaukee%2C+P&rft.aulast=Allen&rft.aufirst=J&rft.date=2001-08-01&rft.volume=25&rft.issue=8&rft.spage=1119&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The critical dimension of ethnicity in liver cirrhosis mortality statistics. AN - 71092891; 11505049 AB - In 1997, liver cirrhosis was the 10th leading cause of death in the United States. Beginning in the 1950s, liver cirrhosis mortality rates have been consistently higher for black than for white men and women. There has been a gradual adoption of the recommendation that all death certificates include information on the Hispanic origin of decedents, with universal adoption in the 1997 data year. It is the purpose of this study to examine the extent to which relative risks for cirrhosis mortality might shift for different demographic groups when Hispanic origin is considered along with the race and sex of the decedent. Age-adjusted death rates were calculated for liver cirrhosis by using public-use data files produced by the National Center for Health Statistics. Trends in cirrhosis mortality rates from 1991 through 1997 are shown for white Hispanic, white non-Hispanic, black Hispanic, and black non-Hispanic men and women. In 1997, white Hispanic men show the highest cirrhosis mortality rates over the period examined, followed by black non-Hispanic and white non-Hispanic men, white Hispanic women, and black non-Hispanic and white non-Hispanic women. Among Hispanic decedents, the largest group was of Mexican ancestry, with large numbers being born outside the United States and having low education levels. The findings of higher risk for cirrhosis mortality among white men and women of Hispanic origin serve to focus new attention on these demographic groups. Collateral analyses of other causes of death do not support alternate explanations of these findings as artifacts of demographic misclassification. Future studies of amounts and patterns of alcohol consumption should include Hispanic origin among demographic factors examined. JF - Alcoholism, clinical and experimental research AU - Stinson, F S AU - Grant, B F AU - Dufour, M C AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. fstinson@mail.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 1181 EP - 1187 VL - 25 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - United States KW - Liver Cirrhosis, Alcoholic -- ethnology KW - Mexico -- ethnology KW - Educational Status KW - Hispanic Americans KW - Sex Characteristics KW - Humans KW - European Continental Ancestry Group KW - Liver Cirrhosis, Alcoholic -- mortality KW - African Americans KW - Male KW - Female KW - Liver Cirrhosis -- ethnology KW - Ethnic Groups KW - Liver Cirrhosis -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71092891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=The+critical+dimension+of+ethnicity+in+liver+cirrhosis+mortality+statistics.&rft.au=Stinson%2C+F+S%3BGrant%2C+B+F%3BDufour%2C+M+C&rft.aulast=Stinson&rft.aufirst=F&rft.date=2001-08-01&rft.volume=25&rft.issue=8&rft.spage=1181&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhalation toxicity studies of the alpha,beta-unsaturated ketones: ethyl vinyl ketone. AN - 71083466; 11498798 AB - The National Toxicology Program is conducting a chemical class study to investigate the structure-activity relationships for the toxicity of alpha,beta-unsaturated ketones. Ethyl vinyl ketone (EVK) was selected for study because it is a representative straight-chain aliphatic alpha,beta-unsaturated ketone with extensive use and widespread exposure. Short-term inhalation studies of EVK were conducted to provide toxicity data for comparison with the related alpha,beta-unsaturated ketones 2-cyclohexene-1-one (CHX) and methyl vinyl ketone (MVK). These data will be used in designing chronic toxicity and carcinogenicity studies of these ketones. Male and female F344 rats and B6C3F1 mice were exposed to 0, 2, 4, or 8 ppm EVK 6 h/day, 5 days/wk for 13 wk. The nasal cavity was the major target organ of EVK in both rats and mice. Pathologic findings in both the olfactory and respiratory epithelium were observed. Lesions consisted primarily of olfactory epithelial necrosis, atrophy and regeneration, and/or hyperplasia and squamous metaplasia of the respiratory epithelium. Squamous metaplasia of the respiratory epithelium was present in all rats and mice exposed to 4 and 8 ppm EVK, and these lesions were more severe in rats than in mice. Few systemic effects were observed in rats and mice exposed to EVK. A transient decrease in total leukocytes due to decrements in lymphocyte and monocyte populations was present in male rats after exposure to 8 ppm for 3 and 21 days; however, this effect was not present after exposure for 13 wk. There were no chemical-related effects on micronucleus formation in mice, or on sperm motility and vaginal cytology in either species. EVK, like other alpha,beta-unsaturated ketones, is a reactive, direct-acting gaseous irritant with toxicity limited primarily to the upper respiratory tract. JF - Inhalation toxicology AU - Morgan, D L AU - Ward, S M AU - Wilson, R E AU - Price, H C AU - O'Connor, R W AU - Seely, J C AU - Cunningham, M L AD - National Institute of Environmental Health Sciences/National Toxicology Program, PO Box 12233, Research Triangle Park, NC 27709, USA. morgand@niehs.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 633 EP - 658 VL - 13 IS - 8 SN - 0895-8378, 0895-8378 KW - Pentanones KW - 0 KW - 1-pentene-3-one KW - R0053Y1AZ7 KW - Index Medicus KW - Animals KW - Sex Characteristics KW - Vagina -- pathology KW - Mice KW - Sperm Motility -- drug effects KW - Respiratory System -- pathology KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Micronucleus Tests KW - Body Weight -- drug effects KW - Administration, Inhalation KW - Species Specificity KW - Female KW - Male KW - Organ Size -- drug effects KW - Pentanones -- toxicity KW - Pentanones -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71083466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inhalation+toxicology&rft.atitle=Inhalation+toxicity+studies+of+the+alpha%2Cbeta-unsaturated+ketones%3A+ethyl+vinyl+ketone.&rft.au=Morgan%2C+D+L%3BWard%2C+S+M%3BWilson%2C+R+E%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BSeely%2C+J+C%3BCunningham%2C+M+L&rft.aulast=Morgan&rft.aufirst=D&rft.date=2001-08-01&rft.volume=13&rft.issue=8&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Inhalation+toxicology&rft.issn=08958378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Androgen deprivation therapy for prostate cancer chemoprevention: current status and future directions for agent development. AN - 71083417; 11502457 AB - Prostate cancer chemoprevention is defined as the administration of natural and synthetic agents that inhibit >/=1 steps in the natural history of prostate carcinogenesis. The goal is to find agents that modulate the progression from normal epithelium to dysplasia to high-grade prostatic intraepithelial neoplasia (HGPIN) to locally invasive cancer and systemic disease. Another important goal for chemoprevention is the maintenance of an androgen-sensitive clinical state and delay of the emergence of androgen independence. There is a strong rationale for androgen deprivation therapy (ADT) as a chemoprevention strategy for prostate cancer based on evidence from epidemiologic, experimental, molecular pathophysiologic, and randomized, controlled clinical trials. This includes the fact that HGPIN, the most likely precursor of invasive cancer, is androgen dependent and responds to ADT. Although the large, phase-3 Prostate Cancer Prevention Trial (PCPT) of finasteride versus placebo has established the feasibility and role of ADT for primary prevention, nevertheless, limitations of the anticipated treatment-effect size (eg, 25% reduction) and the potential for selection of androgen resistance provide incentive for finding other effective chemopreventive agents. The availability of novel noncytotoxic pharmaceutical and natural products in clinical development create opportunities for improving the therapeutic index through the principles of combination therapy. The emergence of new powerful tools, such as gene chip complementary DNA microarrays for multiplex gene expression profiling, will accelerate the identification of new molecular targets and the design of rational combinations. Several agent classes have a strong basis for combination with ADT, including antiproliferatives, antioxidant micronutrients (selenium), antiestrogens, and nonsteroidal anti-inflammatory drugs (selective cyclooxygenase-2 inhibitors). JF - Urology AU - Lieberman, R AD - Prostate and Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland 20852, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 83 EP - 90 VL - 58 IS - 2 Suppl 1 KW - Androgen Antagonists KW - 0 KW - Antineoplastic Agents, Hormonal KW - Finasteride KW - 57GNO57U7G KW - Index Medicus KW - Gene Expression Profiling KW - Prostatic Intraepithelial Neoplasia -- drug therapy KW - Prostatic Intraepithelial Neoplasia -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Finasteride -- therapeutic use KW - Chemoprevention -- methods KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Drug Design KW - Chemoprevention -- trends KW - Male KW - Prostatic Intraepithelial Neoplasia -- prevention & control KW - Androgen Antagonists -- therapeutic use KW - Prostatic Neoplasms -- genetics KW - Prostatic Neoplasms -- prevention & control KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71083417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urology&rft.atitle=Androgen+deprivation+therapy+for+prostate+cancer+chemoprevention%3A+current+status+and+future+directions+for+agent+development.&rft.au=Lieberman%2C+R&rft.aulast=Lieberman&rft.aufirst=R&rft.date=2001-08-01&rft.volume=58&rft.issue=2+Suppl+1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Urology&rft.issn=1527-9995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats. AN - 71075146; 11493028 AB - Exogenous application of transforming growth factors-beta (TGF beta) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGF beta trophic factors, we transplanted these tissues directly into the substantia nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K(+)-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts. In contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K(+)-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors. Copyright 2001 Academic Press. JF - Neurobiology of disease AU - Borlongan, C V AU - Zhou, F C AU - Hayashi, T AU - Su, T P AU - Hoffer, B J AU - Wang, Y AD - Cellular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 636 EP - 646 VL - 8 IS - 4 SN - 0969-9961, 0969-9961 KW - Gdnf protein, rat KW - 0 KW - Glial Cell Line-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neuroprotective Agents KW - Sympatholytics KW - Oxidopamine KW - 8HW4YBZ748 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Age Factors KW - Kidney -- metabolism KW - Corpus Striatum -- metabolism KW - Dopamine -- metabolism KW - Behavior, Animal KW - Transplants KW - Rats KW - Rats, Sprague-Dawley KW - Kidney -- cytology KW - Enzyme-Linked Immunosorbent Assay KW - Substantia Nigra -- surgery KW - Substantia Nigra -- cytology KW - Male KW - Nerve Tissue Proteins -- analysis KW - Neuroprotective Agents -- analysis KW - Kidney Transplantation KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neuroprotective Agents -- metabolism KW - Neurons -- enzymology KW - Nerve Tissue Proteins -- metabolism KW - Parkinsonian Disorders -- surgery KW - Parkinsonian Disorders -- pathology KW - Fetal Tissue Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71075146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=Involvement+of+GDNF+in+neuronal+protection+against+6-OHDA-induced+parkinsonism+following+intracerebral+transplantation+of+fetal+kidney+tissues+in+adult+rats.&rft.au=Borlongan%2C+C+V%3BZhou%2C+F+C%3BHayashi%2C+T%3BSu%2C+T+P%3BHoffer%2C+B+J%3BWang%2C+Y&rft.aulast=Borlongan&rft.aufirst=C&rft.date=2001-08-01&rft.volume=8&rft.issue=4&rft.spage=636&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=09699961&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Administration of G--CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more donor toxicity than G--CSF alone. AN - 71074457; 11493736 AB - G-CSF with or without dexamethasone is becoming the standard agent for mobilizing granulocytes for transfusion. The purpose of this study was to determine if the toxicities of G--CSF with or without dexamethasone are offset by greater collection yields and to define the minimum interval that should separate sequential collections. Twenty donors were studied on three occasions. They were given either dexamethasone (8 mg, by mouth) plus a placebo injection, G--CSF (5 microg/kg, given subcutaneously) plus placebo capsules, or G--CSF plus dexamethasone. Granulocytes were collected by apheresis. A donor symptom survey was administered, and cell counts and blood chemistries were assessed before collection and 1, 2, 7, 14, 21, 28, and 35 days after collection. More granulocytes were collected when G--CSF was given than when dexamethasone was given (41.1 +/- 20.4 x 10(9) vs. 21.0 +/- 10.0 x 10(9); p<0.001), but the use of G--CSF plus dexamethasone produced the greatest yields (67.1 +/- 22.0 x 10(9); p<0.002). When the donors were given dexamethasone alone, 58 percent experienced at least one symptom, compared to 85 percent of those given G--CSF and 75 percent of those given G--CSF plus dexamethasone. In all three regimens, platelet counts fell 19 percent to 24 percent after collection and remained below baseline for 7 to 14 days. Granulocyte counts returned to baseline within 3 to 7 days, but, in all three regimens, a mild granulocytopenia occurred 21 days after collection. With each of the regimens, blood chemistries changed, but the changes were mild and most returned to baseline within 7 days; however, changes in albumin, bilirubin, and AST persisted until 28 days after collection. These results support the use of G--CSF plus dexamethasone in granulocyte donors. G--CSF plus dexamethasone resulted in greater granulocyte yields than either agent alone and was associated with donor symptoms and changes in blood cell counts and chemistries similar to those seen with G--CSF alone or dexamethasone alone. Granulocytes can be safely collected a second time after a 7-day interval; however, for regular donors, it may be best to separate collections by 4 weeks. JF - Transfusion AU - Stroncek, D F AU - Yau, Y Y AU - Oblitas, J AU - Leitman, S F AD - Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. dstroncek@dtm.cc.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 1037 EP - 1044 VL - 41 IS - 8 SN - 0041-1132, 0041-1132 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Blood Pressure KW - Double-Blind Method KW - Humans KW - Blood -- drug effects KW - Blood -- metabolism KW - Blood Cell Count KW - Body Weight KW - Drug Therapy, Combination KW - Prospective Studies KW - Blood Component Removal KW - Adult KW - Middle Aged KW - Female KW - Male KW - Hematopoietic Stem Cell Mobilization -- standards KW - Dexamethasone -- toxicity KW - Hematopoietic Stem Cell Mobilization -- methods KW - Dexamethasone -- pharmacology KW - Dexamethasone -- administration & dosage KW - Granulocytes -- drug effects KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Granulocyte Colony-Stimulating Factor -- toxicity KW - Granulocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71074457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transfusion&rft.atitle=Administration+of+G--CSF+plus+dexamethasone+produces+greater+granulocyte+concentrate+yields+while+causing+no+more+donor+toxicity+than+G--CSF+alone.&rft.au=Stroncek%2C+D+F%3BYau%2C+Y+Y%3BOblitas%2C+J%3BLeitman%2C+S+F&rft.aulast=Stroncek&rft.aufirst=D&rft.date=2001-08-01&rft.volume=41&rft.issue=8&rft.spage=1037&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Presenilin mutations and calcium signaling defects in the nervous and immune systems. AN - 71071534; 11494322 AB - Presenilin-1 (PS1) is thought to regulate cell differentiation and survival by modulating the Notch signaling pathway. Mutations in PS1 have been shown to cause early-onset inherited forms of Alzheimer's disease (AD) by a gain-of-function mechanism that alters proteolytic processing of the amyloid precursor protein (APP) resulting in increased production of neurotoxic forms of amyloid beta-peptide. The present article considers a second pathogenic mode of action of PS1 mutations, a defect in cellular calcium signaling characterized by overfilling of endoplasmic reticulum (ER) calcium stores and altered capacitive calcium entry; this abnormality may impair synaptic plasticity and sensitize neurons to apoptosis and excitotoxicity. The calcium signaling defect has also been documented in lymphocytes, suggesting a contribution of immune dysfunction to the pathogenesis of AD. A better understanding of the calcium signaling defect resulting from PS1 mutations may lead to the development of novel preventative and therapeutic strategies for disorders of the nervous and immune systems. Copyright 2001 John Wiley & Sons, Inc. JF - BioEssays : news and reviews in molecular, cellular and developmental biology AU - Mattson, M P AU - Chan, S L AU - Camandola, S AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 733 EP - 744 VL - 23 IS - 8 SN - 0265-9247, 0265-9247 KW - Amyloid beta-Protein Precursor KW - 0 KW - Membrane Proteins KW - PSEN1 protein, human KW - Presenilin-1 KW - Receptors, Notch KW - Index Medicus KW - Animals KW - Alzheimer Disease -- genetics KW - Immune System -- physiopathology KW - Humans KW - Nervous System -- physiopathology KW - Amyloid beta-Protein Precursor -- physiology KW - Lymphocytes -- physiology KW - Mutation KW - Models, Biological KW - Amyloid beta-Protein Precursor -- genetics KW - Calcium Signaling -- genetics KW - Membrane Proteins -- genetics KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71071534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioEssays+%3A+news+and+reviews+in+molecular%2C+cellular+and+developmental+biology&rft.atitle=Presenilin+mutations+and+calcium+signaling+defects+in+the+nervous+and+immune+systems.&rft.au=Mattson%2C+M+P%3BChan%2C+S+L%3BCamandola%2C+S&rft.aulast=Mattson&rft.aufirst=M&rft.date=2001-08-01&rft.volume=23&rft.issue=8&rft.spage=733&rft.isbn=&rft.btitle=&rft.title=BioEssays+%3A+news+and+reviews+in+molecular%2C+cellular+and+developmental+biology&rft.issn=02659247&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: sequence and tumor biology matters. Commentary re: P. Münster et al., Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. Clin. Cancer Res., 7: 2228-2236, 2001. AN - 71071054; 11489788 JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Sausville, E A AD - Developmental Therapeutics Program, National Cancer Institute, 6130 Executive Boulevard, Rockville, MD 20852, USA. sausville@nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 2155 EP - 2158 VL - 7 IS - 8 SN - 1078-0432, 1078-0432 KW - Anti-Bacterial Agents KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Benzoquinones KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Retinoblastoma Protein KW - Rifabutin KW - 1W306TDA6S KW - tanespimycin KW - 4GY0AVT3L4 KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Rifabutin -- analogs & derivatives KW - Breast Neoplasms -- physiopathology KW - Retinoblastoma Protein -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - HSP90 Heat-Shock Proteins -- physiology KW - Retinoblastoma Protein -- physiology KW - HSP90 Heat-Shock Proteins -- drug effects KW - Rifabutin -- pharmacology KW - Breast Neoplasms -- pathology KW - Apoptosis -- drug effects KW - Drug Synergism KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Anti-Bacterial Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71071054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Combining+cytotoxics+and+17-allylamino%2C+17-demethoxygeldanamycin%3A+sequence+and+tumor+biology+matters.+Commentary+re%3A+P.+M%C3%BCnster+et+al.%2C+Modulation+of+Hsp90+function+by+ansamycins+sensitizes+breast+cancer+cells+to+chemotherapy-induced+apoptosis+in+an+RB-+and+schedule-dependent+manner.+Clin.+Cancer+Res.%2C+7%3A+2228-2236%2C+2001.&rft.au=Sausville%2C+E+A&rft.aulast=Sausville&rft.aufirst=E&rft.date=2001-08-01&rft.volume=7&rft.issue=8&rft.spage=2155&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-08-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Clin Cancer Res. 2001 Aug;7(8):2228-36 [11489796] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo site-directed mutagenesis using oligonucleotides. AN - 71065066; 11479573 AB - Functional characterization of the genes of higher eukaryotes has been aided by their expression in model organisms and by analyzing site-specific changes in homologous genes in model systems such as the yeast Saccharomyces cerevisiae. Modifying sequences in yeast or other organisms such that no heterologous material is retained requires in vitro mutagenesis together with subcloning. PCR-based procedures that do not involve cloning are inefficient or require multistep reactions that increase the risk of additional mutations. An alternative approach, demonstrated in yeast, relies on transformation with an oligonucleotide, but the method is restricted to the generation of mutants with a selectable phenotype. Oligonucleotides, when combined with gap repair, have also been used to modify plasmids in yeast; however, this approach is limited by restriction-site availability. We have developed a mutagenesis approach in yeast based on transformation by unpurified oligonucleotides that allows the rapid creation of site-specific DNA mutations in vivo. A two-step, cloning-free process, referred to as delitto perfetto, generates products having only the desired mutation, such as a single or multiple base change, an insertion, a small or a large deletion, or even random mutations. The system provides for multiple rounds of mutation in a window up to 200 base pairs. The process is RAD52 dependent, is not constrained by the distribution of naturally occurring restriction sites, and requires minimal DNA sequencing. Because yeast is commonly used for random and selective cloning of genomic DNA from higher eukaryotes such as yeast artificial chromosomes, the delitto perfetto strategy also provides an efficient way to create precise changes in mammalian or other DNA sequences. JF - Nature biotechnology AU - Storici, F AU - Lewis, L K AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 773 EP - 776 VL - 19 IS - 8 SN - 1087-0156, 1087-0156 KW - Oligonucleotides KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Escherichia coli -- metabolism KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Transformation, Genetic KW - Models, Genetic KW - Genetic Vectors KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Oligonucleotides -- metabolism KW - Mutation KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - Mutagenesis, Insertional -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71065066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+biotechnology&rft.atitle=In+vivo+site-directed+mutagenesis+using+oligonucleotides.&rft.au=Storici%2C+F%3BLewis%2C+L+K%3BResnick%2C+M+A&rft.aulast=Storici&rft.aufirst=F&rft.date=2001-08-01&rft.volume=19&rft.issue=8&rft.spage=773&rft.isbn=&rft.btitle=&rft.title=Nature+biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. AN - 71062200; 11485987 AB - Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose disposal in response to insulin is impaired. We have developed a transgenic mouse with a dominant-negative insulin-like growth factor-I receptor (KR-IGF-IR) specifically targeted to the skeletal muscle. Expression of KR-IGF-IR resulted in the formation of hybrid receptors between the mutant and the endogenous IGF-I and insulin receptors, thereby abrogating the normal function of these receptors and leading to insulin resistance. Pancreatic beta-cell dysfunction developed at a relative early age, resulting in diabetes. These mice provide an excellent model to study the molecular mechanisms underlying the development of human type 2 diabetes. JF - Genes & development AU - Fernández, A M AU - Kim, J K AU - Yakar, S AU - Dupont, J AU - Hernandez-Sanchez, C AU - Castle, A L AU - Filmore, J AU - Shulman, G I AU - Le Roith, D AD - Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/08/01/ PY - 2001 DA - 2001 Aug 01 SP - 1926 EP - 1934 VL - 15 IS - 15 SN - 0890-9369, 0890-9369 KW - Blood Glucose KW - 0 KW - Fatty Acids, Nonesterified KW - Insulin KW - Triglycerides KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Receptor, Insulin KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Triglycerides -- blood KW - Animals KW - Humans KW - Aging KW - Liver -- metabolism KW - Prediabetic State -- physiopathology KW - Prediabetic State -- genetics KW - Insulin -- pharmacology KW - Insulin -- secretion KW - Mice KW - Mice, Transgenic KW - Mutagenesis, Site-Directed KW - Hyperinsulinism KW - Prediabetic State -- blood KW - Triglycerides -- metabolism KW - Glucose Clamp Technique KW - Fatty Acids, Nonesterified -- blood KW - Islets of Langerhans -- secretion KW - Receptor, IGF Type 1 -- physiology KW - Receptor, Insulin -- genetics KW - Blood Glucose -- metabolism KW - Glucose -- metabolism KW - Insulin Resistance -- genetics KW - Receptor, IGF Type 1 -- genetics KW - Diabetes Mellitus, Type 2 -- genetics KW - Diabetes Mellitus, Type 2 -- physiopathology KW - Diabetes Mellitus, Type 2 -- blood KW - Receptor, Insulin -- physiology KW - Muscle, Skeletal -- metabolism KW - Muscle, Skeletal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71062200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=Functional+inactivation+of+the+IGF-I+and+insulin+receptors+in+skeletal+muscle+causes+type+2+diabetes.&rft.au=Fern%C3%A1ndez%2C+A+M%3BKim%2C+J+K%3BYakar%2C+S%3BDupont%2C+J%3BHernandez-Sanchez%2C+C%3BCastle%2C+A+L%3BFilmore%2C+J%3BShulman%2C+G+I%3BLe+Roith%2C+D&rft.aulast=Fern%C3%A1ndez&rft.aufirst=A&rft.date=2001-08-01&rft.volume=15&rft.issue=15&rft.spage=1926&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Invest. 1999 Nov;104(9):1257-64 [10545524] Nature. 1995 Sep 14;377(6545):151-5 [7675081] Am J Physiol Endocrinol Metab. 2000 Apr;278(4):E729-37 [10751208] J Clin Invest. 2000 Jun;105(12):1791-7 [10862794] Diabetes. 1998 Jan;47(1):87-92 [9421379] Nat Genet. 1996 Jan;12(1):106-9 [8528241] EMBO J. 1996 Apr 1;15(7):1542-7 [8612577] Annu Rev Med. 1996;47:509-31 [8712800] Diabetes. 1996 Jul;45(7):869-75 [8666135] J Clin Invest. 1996 Dec 15;98(12):2887-93 [8981937] J Clin Invest. 1997 Dec 1;100(11):2900-8 [9389757] Am J Physiol. 1998 Feb;274(2 Pt 1):E309-16 [9486163] Nat Genet. 1998 Nov;20(3):294-8 [9806552] Mol Cell. 1998 Nov;2(5):559-69 [9844629] Cell. 1999 Feb 5;96(3):329-39 [10025399] Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7324-9 [10377413] J Biol Chem. 1999 Jul 23;274(30):20791-5 [10409618] Nat Med. 2000 Aug;6(8):924-8 [10932232] Mol Cell. 2000 Jul;6(1):87-97 [10949030] Brain Res Mol Brain Res. 1989 Jul;6(1):69-76 [2770453] N Engl J Med. 1990 Jan 25;322(4):223-8 [2403659] Mol Cell Biol. 1991 Jun;11(6):3070-4 [2038318] J Cell Biochem. 1992 Jan;48(1):43-50 [1316361] J Cell Biochem. 1992 Feb;48(2):136-40 [1320041] J Biol Chem. 1993 Feb 5;268(4):2655-61 [7679099] N Engl J Med. 1993 Dec 30;329(27):1988-92 [8247074] Ann Intern Med. 1994 Jan 1;120(1):47-55 [8250456] J Biol Chem. 1994 Jun 10;269(23):16034-40 [8206901] Endocr Rev. 1995 Apr;16(2):143-63 [7540132] Diabetologia. 1999 Dec;42(12):1441-2 [10651265] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methamphetamine causes differential regulation of pro-death and anti-death Bcl-2 genes in the mouse neocortex. AN - 71061665; 11481222 AB - Bcl-2, an inner mitochondrial membrane protein, inhibits apoptotic neuronal cell death. Expression of Bcl-2 inhibits cell death by decreasing the net cellular generation of reactive oxygen species. Studies by different investigators have provided unimpeachable evidence of a role for oxygen-based free radicals in methamphetamine (METH) -induced neurotoxicity. In addition, studies from our laboratory have shown that immortalized rat neuronal cells that overexpress Bcl-2 are protected against METH-induced apoptosis in vitro. Moreover, the amphetamines can cause differential changes in the expression of Bcl-X splice variants in primary cortical cell cultures. These observations suggested that METH might also cause perturbations of Bcl-2-related genes when administered to rodents. Thus, the present study was conducted to determine whether the use of METH might indeed be associated with transcriptional and translational changes in the expression of Bcl-2-related genes in the mouse brain. Here we report that a toxic regimen of METH did cause significant increases in the pro-death Bcl-2 family genes BAD, BAX, and BID. Concomitantly, there were significant decreases in the anti-death genes Bcl-2 and Bcl-XL. These results thus support the notion that injections of toxic doses of METH trigger the activation of the programmed death pathway in the mammalian brain. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Jayanthi, S AU - Deng, X AU - Bordelon, M AU - McCoy, M T AU - Cadet, J L AD - Molecular Neuropsychiatry Section, NIDA-IRP, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 1745 EP - 1752 VL - 15 IS - 10 SN - 0892-6638, 0892-6638 KW - Proto-Oncogene Proteins c-bcl-2 KW - 0 KW - RNA, Messenger KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - In Situ Nick-End Labeling KW - Animals KW - Blotting, Western KW - Kinetics KW - RNA, Messenger -- analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Male KW - Neocortex -- metabolism KW - Neocortex -- cytology KW - Apoptosis -- drug effects KW - Methamphetamine -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Neocortex -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71061665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Methamphetamine+causes+differential+regulation+of+pro-death+and+anti-death+Bcl-2+genes+in+the+mouse+neocortex.&rft.au=Jayanthi%2C+S%3BDeng%2C+X%3BBordelon%2C+M%3BMcCoy%2C+M+T%3BCadet%2C+J+L&rft.aulast=Jayanthi&rft.aufirst=S&rft.date=2001-08-01&rft.volume=15&rft.issue=10&rft.spage=1745&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. AN - 71058698; 11483648 AB - Toxic effects of HIV-1 proteins contribute to altered function and decreased survival of select populations of neurons in HIV-1-infected brain. One such HIV-1 protein, Tat, can activate calcium release from IP3-sensitive intracellular pools, induce calcium influx in neural cells, and, as a result, can increase neuronal cell death. Here, we provide evidence that Tat potentiates excitatory amino acid (glutamate and NMDA) triggered calcium flux, as well as glutamate- and staurosporine-mediated neurotoxicity. Calcium flux in cultured rat hippocampal neurons triggered by the transient application of glutamate or NMDA was facilitated by pre-exposure to Tat. Facilitation of glutamate-triggered calcium flux by Tat was prevented by inhibitors of ADP-ribosylation of G(i)/G(o) proteins (pertussis toxin), protein kinase C (H7 and bisindolymide), and IP3-mediated calcium release (xestospongin C), but was not prevented by an activator of G(s) (cholera toxin) or an inhibitor of protein kinase A (H89). Facilitation of NMDA-triggered calcium flux by Tat was reversed by inhibitors of tyrosine kinase (genestein and herbimycin A) and by an inhibitor of NMDA receptor function (zinc). Tat increased 32P incorporation into NMDA receptor subunits NR2A and NR2B and this effect was blocked by genestein. Subtoxic concentrations of Tat combined with subtoxic concentrations of glutamate or staurosporine increased neuronal cell death significantly. Together, these findings suggest that NMDA receptors play an important role in Tat neurotoxicity and the mechanisms identified may provide additional therapeutic targets for the treatment of HIV-1 associated dementia. JF - Journal of neurochemistry AU - Haughey, N J AU - Nath, A AU - Mattson, M P AU - Slevin, J T AU - Geiger, J D AD - Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 457 EP - 467 VL - 78 IS - 3 SN - 0022-3042, 0022-3042 KW - Enzyme Inhibitors KW - 0 KW - Gene Products, tat KW - Protein Subunits KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Staurosporine KW - H88EPA0A3N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Regression Analysis KW - Animals KW - Cerebral Cortex -- cytology KW - Synaptosomes -- drug effects KW - Spectrometry, Fluorescence KW - Dose-Response Relationship, Drug KW - Brain Chemistry KW - Models, Biological KW - Rats KW - Staurosporine -- pharmacology KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Cells, Cultured KW - Apoptosis -- drug effects KW - Hippocampus -- cytology KW - Enzyme Inhibitors -- pharmacology KW - Synaptosomes -- metabolism KW - Calcium -- metabolism KW - Glutamic Acid -- toxicity KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Gene Products, tat -- toxicity KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Gene Products, tat -- pharmacology KW - Gene Products, tat -- metabolism KW - Glutamic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71058698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=HIV-1+Tat+through+phosphorylation+of+NMDA+receptors+potentiates+glutamate+excitotoxicity.&rft.au=Haughey%2C+N+J%3BNath%2C+A%3BMattson%2C+M+P%3BSlevin%2C+J+T%3BGeiger%2C+J+D&rft.aulast=Haughey&rft.aufirst=N&rft.date=2001-08-01&rft.volume=78&rft.issue=3&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on N-methyl-D-aspartate channels. AN - 71055423; 11483661 AB - Increased oxyradical production and membrane lipid peroxidation occur in neurons under physiological conditions and in neurodegenerative disorders. Lipid peroxidation can alter synaptic plasticity and may increase the vulnerability of neurons to excitotoxicity, but the underlying mechanisms are unknown. We report that 4-hydroxy-2,3-nonenal (4HN), an aldehyde product of lipid peroxidation, exerts a biphasic effect on NMDA-induced current in cultured rat hippocampal neurons with current being increased during the first 2 h and decreased after 6 h. Similarly, 4HN causes an early increase and a delayed decrease in NMDA-induced elevation of intracellular Ca2+ levels. In contrast, 4HN affects neither the ion current nor the Ca2+ response to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). The initial enhancement of NMDA-induced current is associated with increased phosphorylation of the NR1 receptor subunit, whereas the delayed suppression of current is associated with cellular ATP depletion and mitochondrial membrane depolarization. Cell death induced by 4HN is attenuated by an NMDA receptor antagonist, but not by an AMPA receptor antagonist. A secreted form of amyloid precursor protein, previously shown to protect neurons against oxidative and excitotoxic insults, prevented each of the effects of 4HN including the early and late changes in NMDA current, delayed ATP depletion, and cell death. These findings show that the membrane lipid peroxidation product 4HN can modulate NMDA channel activity, suggesting a role for this aldehyde in physiological and pathophysiological responses of neurons to oxidative stress. JF - Journal of neurochemistry AU - Lu, C AU - Chan, S L AU - Haughey, N AU - Lee, W T AU - Mattson, M P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore 21224, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 577 EP - 589 VL - 78 IS - 3 SN - 0022-3042, 0022-3042 KW - Aldehydes KW - 0 KW - Amyloid beta-Protein Precursor KW - Cysteine Proteinase Inhibitors KW - Enzyme Inhibitors KW - Membrane Lipids KW - Receptors, N-Methyl-D-Aspartate KW - Uncoupling Agents KW - Rotenone KW - 03L9OT429T KW - Okadaic Acid KW - 1W21G5Q4N2 KW - N-Methylaspartate KW - 6384-92-5 KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - 4-hydroxy-2-nonenal KW - K1CVM13F96 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cysteine Proteinase Inhibitors -- metabolism KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid -- pharmacology KW - Uncoupling Agents -- pharmacology KW - Precipitin Tests KW - Rotenone -- pharmacology KW - Rats KW - Calcium -- metabolism KW - Microscopy, Fluorescence KW - Patch-Clamp Techniques KW - Phosphorylation KW - Cells, Cultured KW - N-Methylaspartate -- pharmacology KW - Adenosine Triphosphate -- metabolism KW - Hippocampus -- cytology KW - Okadaic Acid -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Amyloid beta-Protein Precursor -- pharmacology KW - Time Factors KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Membrane Lipids -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Lipid Peroxidation KW - Aldehydes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71055423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Selective+and+biphasic+effect+of+the+membrane+lipid+peroxidation+product+4-hydroxy-2%2C3-nonenal+on+N-methyl-D-aspartate+channels.&rft.au=Lu%2C+C%3BChan%2C+S+L%3BHaughey%2C+N%3BLee%2C+W+T%3BMattson%2C+M+P&rft.aulast=Lu&rft.aufirst=C&rft.date=2001-08-01&rft.volume=78&rft.issue=3&rft.spage=577&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemistry of the diazeniumdiolates. I. Structural and spectral characteristics of the [N(O)NO]- functional group. AN - 71054836; 11485376 AB - Ions of structure X[N(O)NO]-, examples of which have seen increasing use as probes for studying the biology of nitric oxide (NO) over the past decade, have a varied chemical history spanning nearly two centuries. Nevertheless, they have not been widely appreciated for their physicochemical similarities. Here we begin a series of systematic inquiries into the fundamental chemistry of such compounds aimed at identifying both the characteristics that justify considering them as a group and the factors that contribute to observed differences in their physicochemical properties. In the present paper, X-ray structures in which X is SO3- (1), O- (2), Ph (3), and Et2N (5), as well as that of the gem-disubstituted carbon derivative CH2[N(O)NO]2-(2) (4), are compared. All their O-N-N-O systems are essentially planar, with cis oxygens and an N-N linkage exhibiting considerable double-bond character. The ultraviolet spectrum of the isolated chromophore consists of a relatively intense ( approximately 6-10 mM(-1) x cm(-1) per [N(O)NO]- group) absorption at 248-250 nm (for 2 and 5) that is red shifted by through-space Stark interactions (e.g., by approximately 10 nm in 1 and 4) as well as by conjugative interaction with X (lambda(max) = 284 nm for 3). Infrared and Raman spectra for the widely used pharmacological probe 5 were determined, with analysis of vibrational modes being aided by comparison with the spectra of the [15N(O)15NO]- isotopomer and density functional theory calculations at the B3LYP/6-311++G** level. To address confusion that has arisen in the literature resulting from rather widespread use of differing trivial designations for this class of compounds, a unifying nomenclature system is recommended in which compounds containing the [N(O)NO]- moiety are named as diazeniumdiolates. It is hoped that these and other efforts to understand and predict the physicochemical similarities and differences among different members of the diazeniumdiolate class will aid in reaping their full potential in the area of rational drug design. Copyright 2001 Academic Press. JF - Nitric oxide : biology and chemistry AU - Keefer, L K AU - Flippen-Anderson, J L AU - George, C AU - Shanklin, A P AU - Dunams, T M AU - Christodoulou, D AU - Saavedra, J E AU - Sagan, E S AU - Bohle, D S AD - Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. keefer@ncifcrf.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 377 EP - 394 VL - 5 IS - 4 SN - 1089-8603, 1089-8603 KW - Anions KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Spectrophotometry, Infrared KW - Chemistry, Physical KW - Chemical Phenomena KW - Spectrophotometry, Ultraviolet KW - Crystallography, X-Ray KW - Terminology as Topic KW - Molecular Probe Techniques KW - Nitric Oxide -- metabolism KW - Anions -- chemistry KW - Nitric Oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71054836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nitric+oxide+%3A+biology+and+chemistry&rft.atitle=Chemistry+of+the+diazeniumdiolates.+I.+Structural+and+spectral+characteristics+of+the+%5BN%28O%29NO%5D-+functional+group.&rft.au=Keefer%2C+L+K%3BFlippen-Anderson%2C+J+L%3BGeorge%2C+C%3BShanklin%2C+A+P%3BDunams%2C+T+M%3BChristodoulou%2C+D%3BSaavedra%2C+J+E%3BSagan%2C+E+S%3BBohle%2C+D+S&rft.aulast=Keefer&rft.aufirst=L&rft.date=2001-08-01&rft.volume=5&rft.issue=4&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Nitric+oxide+%3A+biology+and+chemistry&rft.issn=10898603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. AN - 71054225; 11481353 AB - The present study attempted to identify characteristics that correlated with clinical response to interleukin (IL)-2 therapy in patients with metastatic melanoma. We retrospectively evaluated laboratory and clinical characteristics of 374 consecutive patients with metastatic melanoma treated with high-dose intravenous bolus IL-2 (720,000 IU/kg) from July 1, 1988, to December 31, 1999, at the Surgery Branch of the National Cancer Institute. The overall objective response rate was 15.5%. Pretreatment parameters such as patient demographics, laboratory values, and prior therapy did not correlate with response; however, 53.6% of patients with only subcutaneous and/or cutaneous metastases responded, compared with 12.4% of patients with disease at other sites (P2 =.000001). During therapy, patients who were responders tended to have received more doses during course 1 (16.2 +/- 0.3 doses v 14.5 +/- 0.2 doses; P2 =.0095); however, when limited to patients who were able to complete both cycles of course 1, there was no statistically significant difference (P2 =.27). Responders had a higher maximum lymphocyte count immediately after therapy compared with nonresponders (P2 =.0026). The development of abnormal thyroid function tests and vitiligo after therapy was associated with response (thyroid-stimulating hormone, P2 =.01; free T4, P2 =.0049; vitiligo, P2 < 10(-6)), although thyroid dysfunction may have been related more to the length of IL-2 therapy than to response. The presence of metastases only to subcutaneous and/or cutaneous sites, lymphocytosis immediately after treatment, and long-term immunologic side effects, especially vitiligo, were associated with antitumor response to IL-2 therapy. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Phan, G Q AU - Attia, P AU - Steinberg, S M AU - White, D E AU - Rosenberg, S A AD - Surgery Branch and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. Y1 - 2001/08/01/ PY - 2001 DA - 2001 Aug 01 SP - 3477 EP - 3482 VL - 19 IS - 15 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Recombinant Proteins KW - Thyrotropin KW - 9002-71-5 KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Injections, Intravenous KW - Thyrotropin -- blood KW - Dose-Response Relationship, Drug KW - Humans KW - Lymphocytosis -- chemically induced KW - Retrospective Studies KW - Aged KW - Thyroxine -- blood KW - Skin Neoplasms -- secondary KW - Skin Neoplasms -- drug therapy KW - Aged, 80 and over KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Recombinant Proteins -- therapeutic use KW - Interleukin-2 -- adverse effects KW - Melanoma -- secondary KW - Interleukin-2 -- therapeutic use KW - Melanoma -- drug therapy KW - Melanoma -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71054225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Factors+associated+with+response+to+high-dose+interleukin-2+in+patients+with+metastatic+melanoma.&rft.au=Phan%2C+G+Q%3BAttia%2C+P%3BSteinberg%2C+S+M%3BWhite%2C+D+E%3BRosenberg%2C+S+A&rft.aulast=Phan&rft.aufirst=G&rft.date=2001-08-01&rft.volume=19&rft.issue=15&rft.spage=3477&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic. AN - 71053506; 11455017 AB - Recent work shows that long-term exposure to low levels of arsenite induces malignant transformation in a rat liver epithelial cell line. Importantly, these chronic arsenic-exposed (CAsE) cells also develop self-tolerance to acute arsenic exposure. Tolerance is accompanied by reduced cellular arsenic accumulation, suggesting a mechanistic basis for reduced arsenic sensitivity. The present study examined the role of xenobiotic export pumps in acquired arsenic tolerance. Microarray analysis of CAsE cells showed increased expression of the genes encoding for glutathione S-transferase Pi (GST-Pi), multidrug resistance-associated protein genes (MRP1/MRP2, which encode for the efflux transporter Mrp1/Mrp2) and the multidrug resistance gene (MDR1, which encodes for the efflux transporter P-glycoprotein). These findings were confirmed at the transcription level by reverse transcription-polymerase chain reaction and at the translation level by Western-blot analysis. Acquired arsenic tolerance was abolished when cells were exposed to ethacrynic acid (an inhibitor of GST-Pi), buthionine sulfoximine (a glutathione synthesis inhibitor), MK571 (a specific inhibitor for Mrps), and PSC833 (a specific inhibitor for P-glycoprotein) in dose-dependent fashions. MK571, PSC833, and buthionine sulfoximine markedly increased cellular arsenic accumulation. Consistent with a role for multidrug resistance efflux pumps in arsenic resistance, CAsE cells were found to be cross-resistant to cytotoxicity of several anticancer drugs, such as vinblastine, doxorubicin, actinomycin-D, and cisplatin, that are also substrates for Mrps and P-glycoprotein. Thus, acquired tolerance to arsenic is associated with increased expression GST-Pi, Mrp1/Mrp2 and P-glycoprotein, which function together to reduce cellular arsenic accumulation. JF - Molecular pharmacology AU - Liu, J AU - Chen, H AU - Miller, D S AU - Saavedra, J E AU - Keefer, L K AU - Johnson, D R AU - Klaassen, C D AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute for Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 302 EP - 309 VL - 60 IS - 2 SN - 0026-895X, 0026-895X KW - Multidrug Resistance-Associated Proteins KW - 0 KW - P-Glycoprotein KW - Glutathione Transferase KW - EC 2.5.1.18 KW - leukotriene-C4 synthase KW - EC 4.4.1.20 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Arsenic Poisoning KW - Oligonucleotide Array Sequence Analysis KW - Cell Survival -- drug effects KW - P-Glycoprotein -- metabolism KW - Cells, Cultured KW - Drug Resistance KW - Arsenic -- toxicity KW - Drug Resistance, Multiple -- physiology KW - Glutathione Transferase -- antagonists & inhibitors KW - ATP-Binding Cassette Transporters -- metabolism KW - Glutathione Transferase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71053506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Overexpression+of+glutathione+S-transferase+II+and+multidrug+resistance+transport+proteins+is+associated+with+acquired+tolerance+to+inorganic+arsenic.&rft.au=Liu%2C+J%3BChen%2C+H%3BMiller%2C+D+S%3BSaavedra%2C+J+E%3BKeefer%2C+L+K%3BJohnson%2C+D+R%3BKlaassen%2C+C+D%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=J&rft.date=2001-08-01&rft.volume=60&rft.issue=2&rft.spage=302&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease. AN - 71050327; 11454793 AB - Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract caused by an abnormal and uncontrolled immune response to one or more normally occurring gut constituents. Given the effects of transforming growth factor beta1 (TGF-beta1) on both the immune system and extracellular matrix, we postulated that alterations in TGF-beta signalling in intestinal epithelial cells may play an important role in the development of IBD. TGF-beta signalling was inactivated in mouse intestine by expressing a dominant negative mutant form of the TGF-beta type II receptor under the control of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF-dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia, and anal prolapse when not maintained under specific pathogen free (SPF) conditions. Under SPF conditions we induced colitis by mixing dextran sodium sulphate (DSS) in drinking water to examine the significance of loss of TGF-beta signalling in the pathogenesis of IBD. Transgenic mice showed increased susceptibility to DSS induced IBD, and elicited increased expression of major histocompatibility complex class II, generation of autoantibodies against intestinal goblet cells, and increased activity of matrix metalloproteinase in intestinal epithelial cells compared with wild-type littermates challenged with DSS. Deficiency of TGF-beta signalling specifically in the intestine contributes to the development of IBD. Maintenance of TGF-beta signalling may be important in regulating immune homeostasis in the intestine JF - Gut AU - Hahm, K B AU - Im, Y H AU - Parks, T W AU - Park, S H AU - Markowitz, S AU - Jung, H Y AU - Green, J AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Library Dr, Bethesda, MD 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 190 EP - 198 VL - 49 IS - 2 SN - 0017-5749, 0017-5749 KW - Autoantibodies KW - 0 KW - Mucins KW - Muscle Proteins KW - Peptides KW - Proteins KW - Receptors, Transforming Growth Factor beta KW - TFF3 protein, human KW - Transforming Growth Factor beta KW - Trefoil Factor-3 KW - Matrix Metalloproteinase 3 KW - EC 3.4.24.17 KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Germ-Free Life KW - Receptors, Transforming Growth Factor beta -- physiology KW - Humans KW - Autoantibodies -- immunology KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Proteins -- physiology KW - Matrix Metalloproteinase 2 -- physiology KW - Blotting, Western KW - Luminescent Measurements KW - Matrix Metalloproteinase 9 -- physiology KW - Matrix Metalloproteinase 3 -- physiology KW - Goblet Cells -- immunology KW - Genes, MHC Class II KW - Transforming Growth Factor beta -- physiology KW - Inflammatory Bowel Diseases -- physiopathology KW - Cell Communication -- physiology KW - Inflammatory Bowel Diseases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71050327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=Loss+of+transforming+growth+factor+beta+signalling+in+the+intestine+contributes+to+tissue+injury+in+inflammatory+bowel+disease.&rft.au=Hahm%2C+K+B%3BIm%2C+Y+H%3BParks%2C+T+W%3BPark%2C+S+H%3BMarkowitz%2C+S%3BJung%2C+H+Y%3BGreen%2C+J%3BKim%2C+S+J&rft.aulast=Hahm&rft.aufirst=K&rft.date=2001-08-01&rft.volume=49&rft.issue=2&rft.spage=190&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=00175749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Cell. 1996 Sep;9(3):229-36 [9183654] J Gastroenterol. 1996 Dec;31(6):907-16 [9027661] Gastroenterology. 1997 Sep;113(3):825-32 [9287974] Am J Physiol. 1997 Oct;273(4 Pt 1):G769-75 [9357817] Gastroenterology. 1997 Dec;113(6):1828-35 [9394722] J Exp Med. 1959 Nov 1;110:657-74 [13804543] Gastroenterology. 1997 Jul;113(1):101-6 [9207267] J Clin Invest. 2000 Apr;105(8):1057-65 [10772650] Nature. 1978 Dec 14;276(5689):711-3 [366434] Scand J Immunol. 1980;12(1):77-82 [6997989] Gastroenterology. 1984 Dec;87(6):1344-50 [6092199] Immunology. 1986 May;58(1):9-14 [2423441] Science. 1986 Jul 25;233(4762):437-43 [3726537] EMBO J. 1987 Jul;6(7):1899-904 [2820711] Scand J Gastroenterol Suppl. 1987;139:41-52 [3324299] Gastroenterology. 1990 Mar;98(3):694-702 [1688816] Gastroenterology. 1990 Aug;99(2):447-53 [2365193] Gut. 1990 Dec;31(12):1371-6 [2176171] Cell. 1992 Feb 21;68(4):775-85 [1310899] Nature. 1992 Oct 22;359(6397):693-9 [1436033] J Cell Biochem. 1992 Dec;50(4):400-10 [1469071] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 [8421714] Lab Invest. 1993 Aug;69(2):238-49 [8350599] Cell. 1993 Oct 22;75(2):253-61 [8402910] Cell. 1993 Oct 22;75(2):263-74 [8402911] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9944-8 [8234339] Gastroenterology. 1994 Feb;106(2):533-9 [8299918] Am J Pathol. 1996 Feb;148(2):519-26 [8579114] Gastroenterology. 1996 Apr;110(4):975-84 [8613031] Gene. 1996 Jun 1;171(2):249-53 [8666281] Enzyme Protein. 1996;49(1-3):7-19 [8796994] Gastroenterology. 1997 Jan;112(1):40-5 [8978341] Comment In: Gut. 2001 Aug;49(2):164-5 [11454787] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus. AN - 71038012; 11466437 AB - Neuregulins are highly expressed in the CNS, especially in cholinergic neurons. We have examined the effect of neuregulin on nicotinic acetylcholine receptors (nAChRs) in neurons dissociated from the rat hippocampus. Rapid application of acetylcholine (ACh) induced a rapidly rising and decaying inward current in some of the neurons, which was completely blocked by methyllycaconitine, a specific antagonist of the alpha7 subunit of the nAChR. When the cells were treated with 5 nm neuregulin (NRG1-beta1) for 2-4 d, a twofold increase in amplitude of the peak ACh-induced current was observed, and there was a comparable increase in (125)I-alpha-bungarotoxin binding. The fast ACh-induced peak current was prominent in large neurons that also contained GABA immunoreactivity. These presumptive GABAergic neurons constituted approximately 10% of neurons present in 7- to 9-d-old cultures. In addition to the large inward peak current, ACh also evoked transmitter release from presynaptic nerve terminals. Pharmacologic experiments indicated that the shower of PSCs was mediated by glutamate, with a small minority caused by the action of GABA. Chronic exposure to NRG1-beta1 increased the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC. NRG1-beta1 also increased the percentage of neurons that exhibited ACh-evoked PSCs. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Liu, Y AU - Ford, B AU - Mann, M A AU - Fischbach, G D AD - Section on Developmental Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. liuy@ninds.nih.gov Y1 - 2001/08/01/ PY - 2001 DA - 2001 Aug 01 SP - 5660 EP - 5669 VL - 21 IS - 15 KW - Bungarotoxins KW - 0 KW - Cholinergic Agents KW - Chrna7 protein, rat KW - Excitatory Amino Acid Antagonists KW - Iodine Radioisotopes KW - Neuregulin-1 KW - Nicotinic Antagonists KW - Receptors, Nicotinic KW - alpha7 Nicotinic Acetylcholine Receptor KW - methyllycaconitine KW - 21019-30-7 KW - Glutamic Acid KW - 3KX376GY7L KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Acetylcholine KW - N9YNS0M02X KW - Aconitine KW - X8YN71D5WC KW - Index Medicus KW - Animals KW - Glutamic Acid -- metabolism KW - Hippocampus KW - Binding, Competitive -- physiology KW - Binding, Competitive -- drug effects KW - Acetylcholine -- pharmacology KW - Cell Separation KW - Glutamic Acid -- pharmacology KW - Presynaptic Terminals -- metabolism KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Presynaptic Terminals -- drug effects KW - Patch-Clamp Techniques KW - Excitatory Postsynaptic Potentials -- drug effects KW - Cells, Cultured KW - Bungarotoxins -- pharmacokinetics KW - Nicotinic Antagonists -- pharmacology KW - Cholinergic Agents -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Male KW - Excitatory Postsynaptic Potentials -- physiology KW - Interneurons -- metabolism KW - Receptors, Nicotinic -- metabolism KW - Aconitine -- pharmacology KW - Synaptic Transmission -- drug effects KW - Interneurons -- drug effects KW - Interneurons -- cytology KW - Neuregulin-1 -- pharmacology KW - gamma-Aminobutyric Acid -- metabolism KW - Synaptic Transmission -- physiology KW - Aconitine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71038012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Neuregulins+increase+alpha7+nicotinic+acetylcholine+receptors+and+enhance+excitatory+synaptic+transmission+in+GABAergic+interneurons+of+the+hippocampus.&rft.au=Liu%2C+Y%3BFord%2C+B%3BMann%2C+M+A%3BFischbach%2C+G+D&rft.aulast=Liu&rft.aufirst=Y&rft.date=2001-08-01&rft.volume=21&rft.issue=15&rft.spage=5660&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis. AN - 71034186; 11471049 AB - In the post-genomic era, the laboratory mouse will excel as a premier mammalian system to study normal and disordered biological processes, in part because of low cost, but largely because of the rich opportunities that exist for exploiting genetic tools and technologies in the mouse to systematically determine mammalian gene function. Many robust models of human disease may therefore be developed, and these in turn will provide critical clues to understanding gene function. The full potential of the mouse for understanding many of the neural and behavioral phenotypes of relevance to neuroscientists has yet to be realized. With the full anatomy of the mouse genome at hand, researchers for the first time will be able to move beyond traditional gene-by-gene approaches and take a global view of gene expression patterns crucial for neurobiological processes. In response to an action plan for mouse genomics developed on the basis of recommendations from the scientific community, seven institutes of the National Institutes of Health (NIH) initiated in 1999 a mouse genetics research program that specifically focused on neurobiology and complex behavior. The specific goals of these neuroscience initiatives are to develop high-throughput phenotyping assays and to initiate genome-wide mutagenesis projects to identify hundreds of mutant strains with heritable abnormalities of high relevance to neuroscientists. Assays and mutants generated in these efforts will be made widely available to the scientific community, and such resources will provide neuroscientists unprecedented opportunities to elucidate the molecular mechanisms of neural function and complex behavior. Such research tools ultimately will permit the manipulation and analysis of the mouse genome, as a means of gaining insight into the genetic bases of the mammalian nervous system and its complex disorders. JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Moldin, S O AU - Farmer, M E AU - Chin, H R AU - Battey , J F AD - Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, National Institutes of Health (NIH), 6001 Executive Blvd., Room 7189, MSC 9643, Bethesda, Maryland 20892-9643, USA. smoldin@mail.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 575 EP - 581 VL - 12 IS - 8 SN - 0938-8990, 0938-8990 KW - Index Medicus KW - United States KW - Phenotype KW - Genotype KW - Animals KW - Genetic Testing -- trends KW - Genetic Testing -- methods KW - Models, Genetic KW - National Institutes of Health (U.S.) KW - Genome KW - Neurosciences -- methods KW - Neurosciences -- trends KW - Mice -- genetics KW - Mutagenesis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71034186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=Trans-NIH+neuroscience+initiatives+on+mouse+phenotyping+and+mutagenesis.&rft.au=Moldin%2C+S+O%3BFarmer%2C+M+E%3BChin%2C+H+R%3BBattey+%2C+J+F&rft.aulast=Moldin&rft.aufirst=S&rft.date=2001-08-01&rft.volume=12&rft.issue=8&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-13 N1 - Date created - 2001-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells. AN - 71029529; 11468184 AB - The p12(I) protein, encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 (HTLV-1), is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi. Although p12(I) contains 4 minimal proline-rich, src homology 3-binding motifs (PXXP), a characteristic commonly found in proteins involved in signaling pathways, it has not been known whether p12(I) has a role in modulating intracellular signaling pathways. This study demonstrated that p12(I) binds to the cytoplasmic domain of the interleukin-2 receptor (IL-2R) beta chain that is involved in the recruitment of the Jak1 and Jak3 kinases. As a result of this interaction, p12(I) increases signal transducers and activators of transcription 5 (STAT5) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R beta and gamma(c) chains and Jak3. Transduction of primary human peripheral blood mononuclear cells (PBMCs) with a human immunodeficiency virus type 1-based retroviral vector expressing p12(I) also resulted in increased STAT5 phosphorylation and DNA binding. However, p12(I) could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of alphaCD3 and alphaCD28 antibodies. In addition, the proliferative advantage of p12(I)-transduced PBMCs was evident mainly at low concentrations of IL-2. Together, these data indicate that p12(I) may confer a proliferative advantage on HTLV-1-infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of infected T cells in vivo. (Blood. 2001;98:823-829) JF - Blood AU - Nicot, C AU - Mulloy, J C AU - Ferrari, M G AU - Johnson, J M AU - Fu, K AU - Fukumoto, R AU - Trovato, R AU - Fullen, J AU - Leonard, W J AU - Franchini, G AD - National Cancer Institute, Basic Research Laboratory, Bethesda, MD 20892, USA. Y1 - 2001/08/01/ PY - 2001 DA - 2001 Aug 01 SP - 823 EP - 829 VL - 98 IS - 3 SN - 0006-4971, 0006-4971 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-2 KW - Milk Proteins KW - Oncogene Proteins, Viral KW - Receptors, Interleukin-2 KW - STAT5 Transcription Factor KW - Trans-Activators KW - Transcription Factors KW - Viral Regulatory and Accessory Proteins KW - p12I protein, Human T-lymphotropic virus 1 KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Interleukin-2 -- metabolism KW - HTLV-I Infections -- metabolism KW - Humans KW - Signal Transduction -- drug effects KW - Cell Division -- drug effects KW - Cell Culture Techniques KW - Transcriptional Activation -- drug effects KW - HTLV-I Infections -- pathology KW - Drug Synergism KW - Protein Binding KW - Trans-Activators -- metabolism KW - Interleukin-2 -- pharmacology KW - T-Lymphocytes -- cytology KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - T-Lymphocytes -- drug effects KW - Trans-Activators -- drug effects KW - T-Lymphocytes -- virology KW - Oncogene Proteins, Viral -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71029529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=HTLV-1+p12%28I%29+protein+enhances+STAT5+activation+and+decreases+the+interleukin-2+requirement+for+proliferation+of+primary+human+peripheral+blood+mononuclear+cells.&rft.au=Nicot%2C+C%3BMulloy%2C+J+C%3BFerrari%2C+M+G%3BJohnson%2C+J+M%3BFu%2C+K%3BFukumoto%2C+R%3BTrovato%2C+R%3BFullen%2C+J%3BLeonard%2C+W+J%3BFranchini%2C+G&rft.aulast=Nicot&rft.aufirst=C&rft.date=2001-08-01&rft.volume=98&rft.issue=3&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of type 1 astrocytes on neuronal complexity: a fractal analysis. AN - 71028430; 11465997 AB - Embryonic, ventral spinal cord neurons were grown on poly(d-lysine) (PDL) or on a monolayer of type 1 astrocytes. At various times from 6 h to 2 weeks postplating, cells were fluorescently labeled and fixed with 4% paraformaldehyde. The cell surface immunoreaction allowed visualization of neurons in their entirety, namely, cell bodies and various membranous extensions that included lamellipodia, growth cones, axons, and dendrites. Outlines were drawn for individual neurons and their fractal dimension (D) was calculated. Neurons on poly(d-lysine) reached a peak D at 3 days in vitro, 1 day later than neurons on astrocytes (2 days in vitro). The maximum D was greater for cells on poly(d-lysine) when compared with neurons on astrocytes. In a second experiment the maximum D was similar for neurons on both surfaces but neurons on PDL maintained a higher D for a much longer period than neurons on astrocytes. An examination of fluorescent images revealed that neurons on poly(d-lysine) exhibited lamellipodia and large growth cones for several days and these structures were likely responsible for the high D seen in these cells. These structures were rarely observed in neurons plated on astrocytes. Interestingly, D on both surfaces decreased to a similar value at between 1 and 2 weeks in vitro. The trend for D in these cultures, an initial increase to a peak value followed by a decrease to a stable value, is discussed in light of the chemical nature of the two surfaces and synapse formation and stabilization. Copyright 2001 Academic Press. JF - Methods (San Diego, Calif.) AU - Schaffner, A E AU - Ghesquiere, A AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, Rockville, Maryland 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 323 EP - 329 VL - 24 IS - 4 SN - 1046-2023, 1046-2023 KW - Tetanus Toxin KW - 0 KW - Polylysine KW - 25104-18-1 KW - Index Medicus KW - Rats KW - Microscopy, Fluorescence KW - Animals KW - Polylysine -- pharmacology KW - Cells, Cultured KW - Spinal Cord -- embryology KW - Time Factors KW - Tetanus Toxin -- pharmacology KW - Models, Theoretical KW - Fractals KW - Neurons -- metabolism KW - Neurons -- physiology KW - Astrocytes -- physiology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71028430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+%28San+Diego%2C+Calif.%29&rft.atitle=The+effect+of+type+1+astrocytes+on+neuronal+complexity%3A+a+fractal+analysis.&rft.au=Schaffner%2C+A+E%3BGhesquiere%2C+A&rft.aulast=Schaffner&rft.aufirst=A&rft.date=2001-08-01&rft.volume=24&rft.issue=4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Methods+%28San+Diego%2C+Calif.%29&rft.issn=10462023&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GABA(B) receptors mediate motility signals for migrating embryonic cortical cells. AN - 71021146; 11459764 AB - During development, postmitotic neurons migrate from germinal regions into the cortical plate (cp), where lamination occurs. In rats, GABA is transiently expressed in the cp, near target destinations for migrating neurons. In vitro GABA stimulates neuronal motility, suggesting cp cells release GABA, which acts as a chemoattractant during corticogenesis. Pharmacological studies indicate GABA stimulates migration via GABA(B)-receptor (GABA(B)-R) activation. Using immunohistochemistry, RT-PCR and Western blotting, we examined embryonic cortical cell expression of GABA(B)-Rs in vivo. At E17, GABA(B)-R1(+) cells were identified in the ventricular zone (vz) and cp. RT-PCR and Western blotting demonstrated the presence of GABA(B)-R1a and GABA(B)-R1b mRNA and proteins. Using immuno- cytochemistry, GABA(B)-R expression was examined in vz and cp cell dissociates before and after migration to GABA in an in vitro chemotaxis assay. GABA-induced migration resulted in an increase of GABA(B)-R(+) cells in the migrated population. While 70% of migrated cells were immunopositive. We used a microchemotaxis assay to analyze cp cell release of diffusible chemotropic factor(s). In vitro, cp dissociates induced vz cell migration in a cell density-dependent manner that was blocked by micromolar saclofen (a GABA(B)-R antagonist). HPLC demonstrated cp cells release micromolar levels of GABA and taurine in several hours. Micromolar levels of both molecules stimulated cell migration that was blocked by micromolar saclofen. Thus, migratory cortical cells express GABA(B)-Rs, cp cells release GABA and taurine, and both molecules stimulate cortical cell movement. Together these findings suggest GABA and/or taurine act as chemoattractants for neurons during rat cortical histogenesis via mechanisms involving GABA(B)-Rs. JF - Cerebral cortex (New York, N.Y. : 1991) AU - Behar, T N AU - Smith, S V AU - Kennedy, R T AU - McKenzie, J M AU - Maric, I AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 744 EP - 753 VL - 11 IS - 8 SN - 1047-3211, 1047-3211 KW - Amino Acids KW - 0 KW - Antimetabolites KW - Chemotactic Factors KW - Receptors, GABA-B KW - Taurine KW - 1EQV5MLY3D KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Animals KW - Taurine -- metabolism KW - Amino Acids -- analysis KW - Cell Separation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Chromatography, High Pressure Liquid KW - Pregnancy KW - Rats KW - Signal Transduction -- physiology KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Amino Acids -- isolation & purification KW - Signal Transduction -- drug effects KW - gamma-Aminobutyric Acid -- metabolism KW - Immunohistochemistry KW - Chemotactic Factors -- pharmacology KW - Female KW - Cerebral Cortex -- cytology KW - Receptors, GABA-B -- physiology KW - Cerebral Cortex -- embryology KW - Cell Movement -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71021146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cerebral+cortex+%28New+York%2C+N.Y.+%3A+1991%29&rft.atitle=GABA%28B%29+receptors+mediate+motility+signals+for+migrating+embryonic+cortical+cells.&rft.au=Behar%2C+T+N%3BSmith%2C+S+V%3BKennedy%2C+R+T%3BMcKenzie%2C+J+M%3BMaric%2C+I%3BBarker%2C+J+L&rft.aulast=Behar&rft.aufirst=T&rft.date=2001-08-01&rft.volume=11&rft.issue=8&rft.spage=744&rft.isbn=&rft.btitle=&rft.title=Cerebral+cortex+%28New+York%2C+N.Y.+%3A+1991%29&rft.issn=10473211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Illicit drug use in one's social network and in one's neighborhood predicts individual heroin and cocaine use. AN - 71019178; 11454498 AB - The nature of competing social environmental factors' influence on substance abuse is unclear. A longitudinal study was undertaken to determine the relative power of social network and neighborhood characteristics to predict continuing illicit drug use. Three hundred forty-two inner-city adults with a history of injection drug use were followed for 1 year; their heroin and cocaine use were assessed semiannually. Multiple logistic regression models were fit to determine the degree to which social network and neighborhood characteristics, assessed at baseline, predicted continuing heroin and/or cocaine use throughout the study period. Two hundred thirty-six (69%) participants reported continuing heroin and/or cocaine use. Drug use by members of the social network was a stronger predictor of participants' continuing drug use (OR = 4.31, 95% CI 2.51 to 7.40) than was a high level of drug-related arrests in the participant's neighborhood (OR = 2.41, 95% CI 1.24 to 4.71), after adjusting for drug treatment and demographic variables. Both seemed to have independent effects on study participants' drug use. These findings reiterate the importance of breaking ties with drug-using associates, even for those who reside in high-risk environments. Further work is needed to develop interventions that increase drug users' success in altering social network composition or also treat drug-using network members. JF - Annals of epidemiology AU - Schroeder, J R AU - Latkin, C A AU - Hoover, D R AU - Curry, A D AU - Knowlton, A R AU - Celentano, D D AD - Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 389 EP - 394 VL - 11 IS - 6 SN - 1047-2797, 1047-2797 KW - Index Medicus KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Social Support KW - Maryland -- epidemiology KW - Longitudinal Studies KW - Urban Population KW - Male KW - Female KW - Heroin Dependence -- epidemiology KW - Cocaine-Related Disorders -- epidemiology KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71019178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+epidemiology&rft.atitle=Illicit+drug+use+in+one%27s+social+network+and+in+one%27s+neighborhood+predicts+individual+heroin+and+cocaine+use.&rft.au=Schroeder%2C+J+R%3BLatkin%2C+C+A%3BHoover%2C+D+R%3BCurry%2C+A+D%3BKnowlton%2C+A+R%3BCelentano%2C+D+D&rft.aulast=Schroeder&rft.aufirst=J&rft.date=2001-08-01&rft.volume=11&rft.issue=6&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection of nigral neurons by GDNF-engineered marrow cell transplantation. AN - 71017556; 11463477 AB - Marrow stromal cells, which have many characteristics of stem cells, populate various non-hematopoietic tissues including the brain. In the present study, the cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease. Following cross-sex intravenous bone marrow transplantation with male donor cells that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow (Control-BMT), female recipient mice were subjected to systemic MPTP injections. Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive nigral neurons and striatal terminal density were observed in the GDNF-BMT mice compared with the Control-BMT group. In addition, following the expected initial behavioral hyperactivity in both groups, a significant difference in motor activity was detected between the two groups. GDNF immunoreactive male donor marrow derived cells were detected in the brains of GDNF-BMT mice but not in controls. These data indicate that marrow derived cells that seed the brain can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain. JF - Neuroscience research AU - Park, K W AU - Eglitis, M A AU - Mouradian, M M AD - Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 315 EP - 323 VL - 40 IS - 4 SN - 0168-0102, 0168-0102 KW - DNA, Complementary KW - 0 KW - Gdnf protein, mouse KW - Glial Cell Line-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neuroprotective Agents KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Motor Activity -- genetics KW - Animals KW - DNA, Complementary -- genetics KW - Tyrosine 3-Monooxygenase -- biosynthesis KW - Mice KW - Cells, Cultured -- cytology KW - Cells, Cultured -- transplantation KW - Transfection -- methods KW - Recovery of Function -- genetics KW - Bone Marrow Cells -- metabolism KW - Cells, Cultured -- metabolism KW - Genetic Vectors KW - Neuroprotective Agents -- metabolism KW - Mice, Inbred C57BL KW - Dopamine -- biosynthesis KW - Behavior, Animal -- physiology KW - Bone Marrow Cells -- cytology KW - Immunohistochemistry KW - Male KW - Female KW - Bone Marrow Transplantation -- methods KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Substantia Nigra -- drug effects KW - Nerve Tissue Proteins -- biosynthesis KW - Nerve Tissue Proteins -- genetics KW - Neurons -- pathology KW - Substantia Nigra -- pathology KW - Parkinsonian Disorders -- therapy KW - Genetic Therapy -- methods KW - Substantia Nigra -- surgery KW - Parkinsonian Disorders -- genetics KW - Parkinsonian Disorders -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71017556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+research&rft.atitle=Protection+of+nigral+neurons+by+GDNF-engineered+marrow+cell+transplantation.&rft.au=Park%2C+K+W%3BEglitis%2C+M+A%3BMouradian%2C+M+M&rft.aulast=Park&rft.aufirst=K&rft.date=2001-08-01&rft.volume=40&rft.issue=4&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Neuroscience+research&rft.issn=01680102&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strand breaks in whole plasmid dna produced by the decay of (125)I in a triplex-forming oligonucleotide. AN - 70996890; 11448236 AB - DNA strand breaks produced by the decay of (125)I positioned against a specific site in plasmid DNA via a triplex-forming oligonucleotide were studied both in the immediate vicinity of the site of the decay with a single nucleotide resolution and in the whole plasmid by measuring the percentages of supercoiled, open-circular and linear forms. The localized breaks are distributed within 10 bp in each direction from the decay site with maxima in both strands just opposite the (125)I-dC residue in the triplex-forming oligonucleotide. The distributions of breaks in the two DNA strands are almost symmetrical, in agreement with the geometry of the pyrimidine motif triplex. We found that about 25% of the double-strand breaks were located outside the 90-bp fragment containing the triplex-forming oligonucleotide binding sequence. The ratio of single- to double-strand breaks in the whole plasmid was 11 for bound triplex-forming oligonucleotide compared to 26 when the triplex-forming oligonucleotide was free in solution. The number of double-strand breaks per decay of (125)I was 0.46 for bound triplex-forming oligonucleotide and 0.17 for free triplex-forming oligonucleotide. Comparing the data on the localized damage and those for the whole plasmid, we concluded that, in addition to DNA breaks that are confined to a helical turn around the (125)I atom, the decay can produce breaks hundreds of base pairs away in the plasmid molecule. This linear plasmid molecule containing radiation-induced damage at a specific DNA site should be useful in studies of the molecular mechanisms of DNA repair. JF - Radiation research AU - Panyutin, I V AU - Luu, A N AU - Panyutin, I G AU - Neumann, R D AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda Maryland 20854, USA. Irina@nmdpet.cc.nih.gov. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 158 EP - 166 VL - 156 IS - 2 SN - 0033-7587, 0033-7587 KW - Iodine Radioisotopes KW - 0 KW - Oligodeoxyribonucleotides KW - Index Medicus KW - Space life sciences KW - Base Sequence KW - DNA Repair KW - Humans KW - In Vitro Techniques KW - Molecular Sequence Data KW - Genes, MDR KW - Plasmids -- genetics KW - DNA Damage KW - Oligodeoxyribonucleotides -- chemistry KW - Iodine Radioisotopes -- adverse effects KW - Oligodeoxyribonucleotides -- chemical synthesis KW - Plasmids -- radiation effects KW - Plasmids -- chemistry KW - Oligodeoxyribonucleotides -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70996890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Strand+breaks+in+whole+plasmid+dna+produced+by+the+decay+of+%28125%29I+in+a+triplex-forming+oligonucleotide.&rft.au=Panyutin%2C+I+V%3BLuu%2C+A+N%3BPanyutin%2C+I+G%3BNeumann%2C+R+D&rft.aulast=Panyutin&rft.aufirst=I&rft.date=2001-08-01&rft.volume=156&rft.issue=2&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of perillic acid, a putative isoprenylation inhibitor, on the cultured rat lens. AN - 70995927; 11446774 AB - Previous studies have demonstrated that agents affecting the cholesterol synthetic pathway can have cataractogenic effects. We have suggested that opacification of cultured lenses resulting from exposure to the cholesterol-lowering agent lovastatin is caused by inhibition of isoprenylation of small GTPases. To test that hypothesis we have investigated the effects of perillic acid, an agent reported to inhibit isoprenylation, on rat lenses in organ culture. Perillic acid caused dose and time dependent opacification of cultured lenses. While the opacities appeared grossly similar to those produced by lovastatin, they differed dramatically when analysed histologically. It also produced marked morphological changes to lens epithelial cells in culture. Analysis of small GTPases in the perillic acid treated cells failed to detect any accumulation in the water soluble fraction as would be expected if isoprenylation was inhibited. Further, studies on the isoprenylation of radiolabelled isoprenoids into proteins in cultured lenses showed no significant decrease following perillic acid exposure. It was concluded that perillic acid causes cataract in this system by a mechanism different from lovastatin and that inhibition of isoprenylation is unlikely to be a primary factor in the perillic acid cataract. Copyright 2001 Academic Press. JF - Experimental eye research AU - Cheng, Q F AU - Rao, P V AU - Zigler, J S AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, 6 Center Drive, MSC 2735, Bethesda, MD 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 239 EP - 245 VL - 73 IS - 2 SN - 0014-4835, 0014-4835 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Cyclohexenes KW - Diterpenes KW - Monoterpenes KW - Terpenes KW - Farnesol KW - 4602-84-0 KW - perillic acid KW - 7694-45-3 KW - Lovastatin KW - 9LHU78OQFD KW - geranylgeraniol KW - AIA02AJA3A KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Protein Prenylation -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - GTP Phosphohydrolases -- analysis KW - Lovastatin -- pharmacology KW - Farnesol -- metabolism KW - Organ Culture Techniques KW - Male KW - Female KW - Diterpenes -- metabolism KW - Cataract -- pathology KW - Lens, Crystalline -- metabolism KW - Lens, Crystalline -- drug effects KW - Cataract -- chemically induced KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Terpenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70995927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+eye+research&rft.atitle=Effect+of+perillic+acid%2C+a+putative+isoprenylation+inhibitor%2C+on+the+cultured+rat+lens.&rft.au=Cheng%2C+Q+F%3BRao%2C+P+V%3BZigler%2C+J+S&rft.aulast=Cheng&rft.aufirst=Q&rft.date=2001-08-01&rft.volume=73&rft.issue=2&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Experimental+eye+research&rft.issn=00144835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thalidomide neuropathy in patients treated for metastatic prostate cancer. AN - 70993026; 11439380 AB - We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection. Copyright 2001 John Wiley & Sons, Inc. JF - Muscle & nerve AU - Molloy, F M AU - Floeter, M K AU - Syed, N A AU - Sandbrink, F AU - Culcea, E AU - Steinberg, S M AU - Dahut, W AU - Pluda, J AU - Kruger, E A AU - Reed, E AU - Figg, W D AD - EMG Section, National Institute of Neurological Disorders and Stroke (NINDS), 10 Center Drive, MSC 1404, Bethesda, Maryland 20892-1404, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 1050 EP - 1057 VL - 24 IS - 8 SN - 0148-639X, 0148-639X KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - Age Factors KW - Sural Nerve -- drug effects KW - Brachial Plexus -- physiopathology KW - Dose-Response Relationship, Drug KW - Neural Conduction -- drug effects KW - Humans KW - Brachial Plexus -- drug effects KW - Electromyography KW - Aged KW - Action Potentials -- drug effects KW - Sural Nerve -- physiopathology KW - Prospective Studies KW - Aged, 80 and over KW - Risk Factors KW - Electrodiagnosis KW - Cohort Studies KW - Neoplasm Metastasis KW - Neurons, Afferent -- drug effects KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Thalidomide -- adverse effects KW - Prostatic Neoplasms -- drug therapy KW - Peripheral Nervous System Diseases -- chemically induced KW - Peripheral Nervous System Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70993026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Muscle+%26+nerve&rft.atitle=Thalidomide+neuropathy+in+patients+treated+for+metastatic+prostate+cancer.&rft.au=Molloy%2C+F+M%3BFloeter%2C+M+K%3BSyed%2C+N+A%3BSandbrink%2C+F%3BCulcea%2C+E%3BSteinberg%2C+S+M%3BDahut%2C+W%3BPluda%2C+J%3BKruger%2C+E+A%3BReed%2C+E%3BFigg%2C+W+D&rft.aulast=Molloy&rft.aufirst=F&rft.date=2001-08-01&rft.volume=24&rft.issue=8&rft.spage=1050&rft.isbn=&rft.btitle=&rft.title=Muscle+%26+nerve&rft.issn=0148639X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Invasive candidiasis stimulates hepatocyte and monocyte production of active transforming growth factor beta. AN - 70989845; 11447193 AB - Candida albicans is an opportunistic fungal pathogen and a major cause of morbidity and mortality in patients with compromised immune function. The cytokine response to tissue invasion by C. albicans can influence the differentiation and function of lymphocytes and other mononuclear cells that are critical components of the host response. While the production of transforming growth factor beta (TGF-beta) has been documented in mice infected with C. albicans and is known to suppress phagocyte function, the cellular source and role of this cytokine in the pathogenesis of systemic candidiasis are not well understood. We have investigated the source of production of TGF-beta by immunohistochemical studies in tissue samples from patients with an uncommon complication of lymphoreticular malignancy, chronic disseminated candidiasis (CDC), and from a neutropenic-rabbit model of CDC. Liver biopsy specimens from patients with documented CDC demonstrated intense staining for extracellular matrix-associated TGF-beta1 within inflammatory granulomas, as well as staining for TGF-beta1 and TGF-beta3 within adjacent hepatocytes. These results correlate with the immunolocalization of TGF-beta observed in livers of infected neutropenic rabbits, using a neutralizing antibody that recognizes the mature TGF-beta protein. Human peripheral blood monocytes incubated with C. albicans in vitro release large amounts of biologically active TGF-beta1. The data demonstrate that local production of active TGF-betas by hepatocytes and by infected mononuclear cells is a component of the response to C. albicans infection that most probably contributes to disease progression in the immunocompromised host. JF - Infection and immunity AU - Letterio, J J AU - Lehrnbecher, T AU - Pollack, G AU - Walsh, T J AU - Chanock, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 5115 EP - 5120 VL - 69 IS - 8 SN - 0019-9567, 0019-9567 KW - TGFB1 protein, human KW - 0 KW - TGFB2 protein, human KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Transforming Growth Factor beta2 KW - Transforming Growth Factor beta3 KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Humans KW - Rabbits KW - Transforming Growth Factor beta -- biosynthesis KW - Liver -- cytology KW - Hepatocytes -- microbiology KW - Monocytes -- cytology KW - Liver -- immunology KW - Monocytes -- immunology KW - Candidiasis -- immunology KW - Hepatocytes -- cytology KW - Transforming Growth Factor beta -- immunology KW - Hepatocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70989845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Invasive+candidiasis+stimulates+hepatocyte+and+monocyte+production+of+active+transforming+growth+factor+beta.&rft.au=Letterio%2C+J+J%3BLehrnbecher%2C+T%3BPollack%2C+G%3BWalsh%2C+T+J%3BChanock%2C+S+J&rft.aulast=Letterio&rft.aufirst=J&rft.date=2001-08-01&rft.volume=69&rft.issue=8&rft.spage=5115&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-07-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1991 Sep 1;174(3):539-45 [1908509] Clin Exp Immunol. 1999 Mar;115(3):491-7 [10193423] Development. 1991 Sep;113(1):183-91 [1764993] J Immunol. 1992 Jun 15;148(12):3912-9 [1534826] Science. 1992 Jul 24;257(5069):545-8 [1636092] Nature. 1992 Oct 22;359(6397):693-9 [1436033] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 [8421714] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3442-6 [7682701] Eur J Immunol. 1993 May;23(5):1034-8 [8477799] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4577-81 [8506302] J Exp Med. 1993 Aug 1;178(2):605-13 [7688028] Ann N Y Acad Sci. 1993 Jun 23;685:713-39 [8363277] Trends Cell Biol. 1999 Jul;9(7):274-9 [10370243] Antimicrob Agents Chemother. 1999 Oct;43(10):2463-7 [10508025] Eur J Immunol. 1993 Sep;23(9):2306-10 [8370407] J Exp Med. 1993 Dec 1;178(6):2207-11 [8245792] Eur J Immunol. 1994 Apr;24(4):793-8 [7908633] Eur J Immunol. 1994 Apr;24(4):909-15 [7908634] J Exp Med. 1994 May 1;179(5):1695-9 [8163946] J Infect Dis. 1994 Jun;169(6):1325-31 [8195611] Eur J Immunol. 1995 Jun;25(6):1559-65 [7614983] Cell. 1995 Jul 28;82(2):287-96 [7628017] J Immunol. 1995 Aug 1;155(3):1349-60 [7636200] J Immunol. 1995 Aug 1;155(3):1450-9 [7636210] Trends Microbiol. 1995 Jun;3(6):237-40 [7648032] Immunol Res. 1995;14(2):148-62 [8530878] Infect Immun. 1999 Dec;67(12):6461-72 [10569764] Curr Opin Hematol. 2000 Jan;7(1):9-15 [10608498] Genes Dev. 2000 Jan 15;14(2):187-97 [10652273] Immunity. 2000 Feb;12(2):171-81 [10714683] N Engl J Med. 2000 May 4;342(18):1350-8 [10793168] Infect Dis Clin North Am. 2000 Sep;14(3):721-39 [10987117] J Immunol. 2000 Nov 1;165(9):4773-7 [11045997] Cell Immunol. 1984 May;85(2):384-95 [6232003] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] J Cell Physiol. 1989 Jan;138(1):79-86 [2910889] J Cell Biol. 1989 Feb;108(2):653-60 [2465297] J Infect Dis. 1990 Apr;161(4):755-60 [2138654] J Immunol. 1990 May 1;144(9):3444-8 [2139455] Growth Factors. 1990;3(1):45-52 [2383401] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3193-8 [8622912] Cancer. 1995 Dec 1;76(11):2357-62 [8635043] Int J Obes Relat Metab Disord. 1996 Mar;20 Suppl 3:S4-8 [8680476] Cytokine. 1996 Jan;8(1):42-8 [8742065] Res Immunol. 1995 Sep-Oct;146(7-8):532-8 [8839158] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3926-31 [9108081] Chem Immunol. 1997;68:70-85 [9329217] Chem Immunol. 1997;68:110-35 [9329219] J Exp Med. 1998 Feb 2;187(3):307-17 [9449711] Annu Rev Immunol. 1998;16:137-61 [9597127] J Infect Dis. 1998 Aug;178(2):589-92 [9697751] J Immunol. 1998 Nov 1;161(9):4709-18 [9794401] Int J Clin Lab Res. 1998;28(3):148-61 [9801925] J Infect Dis. 1998 Dec;178(6):1734-42 [9815227] EMBO J. 1999 Mar 1;18(5):1280-91 [10064594] Nature. 1999 Feb 25;397(6721):710-3 [10067896] Mol Cell Biol. 1999 Apr;19(4):2495-504 [10082515] J Exp Med. 1991 Nov 1;174(5):1209-20 [1940799] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad proteins and hepatocyte growth factor control parallel regulatory pathways that converge on beta1-integrin to promote normal liver development. AN - 70979162; 11438667 AB - Smads serve as intracellular mediators of transforming growth factor beta (TGF-beta) signaling. After phosphorylation by activated type I TGF-beta receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-beta target genes. Mice lacking one copy each of Smad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-beta signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the beta1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the beta1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in the Smad2(+/-); Smad3(+/-) livers. JF - Molecular and cellular biology AU - Weinstein, M AU - Monga, S P AU - Liu, Y AU - Brodie, S G AU - Tang, Y AU - Li, C AU - Mishra, L AU - Deng, C X AD - Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20878, USA. Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 5122 EP - 5131 VL - 21 IS - 15 SN - 0270-7306, 0270-7306 KW - Antigens, CD29 KW - 0 KW - Cadherins KW - DNA-Binding Proteins KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Index Medicus KW - Active Transport, Cell Nucleus KW - Animals KW - Cadherins -- metabolism KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mutagenesis KW - Phenotype KW - Blotting, Western KW - In Situ Hybridization KW - Phosphorylation KW - Cells, Cultured KW - Heterozygote KW - Transforming Growth Factor beta -- metabolism KW - Time Factors KW - Mutation KW - Immunohistochemistry KW - Signal Transduction KW - Cell Adhesion KW - Cell Division KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - Antigens, CD29 -- metabolism KW - Hepatocyte Growth Factor -- genetics KW - Hepatocyte Growth Factor -- metabolism KW - DNA-Binding Proteins -- genetics KW - Liver -- metabolism KW - Liver -- embryology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70979162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Smad+proteins+and+hepatocyte+growth+factor+control+parallel+regulatory+pathways+that+converge+on+beta1-integrin+to+promote+normal+liver+development.&rft.au=Weinstein%2C+M%3BMonga%2C+S+P%3BLiu%2C+Y%3BBrodie%2C+S+G%3BTang%2C+Y%3BLi%2C+C%3BMishra%2C+L%3BDeng%2C+C+X&rft.aulast=Weinstein&rft.aufirst=M&rft.date=2001-08-01&rft.volume=21&rft.issue=15&rft.spage=5122&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Cell Biol. 1999 Sep;1(5):260-6 [10559937] Trends Cell Biol. 1998 Oct;8(10):404-10 [9789329] Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):5-13 [10708948] EMBO J. 2000 Apr 17;19(8):1745-54 [10775259] J Biol Chem. 2000 Nov 24;275(47):36818-22 [11016919] J Cell Biol. 1990 Oct;111(4):1645-50 [2211831] Curr Opin Genet Dev. 1998 Oct;8(5):526-31 [9794819] Oncogene. 1999 Jan 14;18(2):353-64 [9927192] Nat Med. 1999 Feb;5(2):226-30 [9930873] EMBO J. 1999 Mar 1;18(5):1280-91 [10064594] Mol Cell Biol. 1999 Apr;19(4):2495-504 [10082515] Am J Physiol. 1999 Apr;276(4 Pt 1):G1059-68 [10198351] Am J Surg. 1999 Mar;177(3):209-15 [10219856] Science. 1999 Jun 18;284(5422):1998-2003 [10373120] Nature. 1999 Aug 12;400(6745):687-93 [10458166] Nature. 1992 Oct 22;359(6397):693-9 [1436033] Nature. 1995 Feb 23;373(6516):699-702 [7854452] Genes Dev. 1995 Aug 1;9(15):1896-908 [7544313] Nat Genet. 1995 Dec;11(4):409-14 [7493021] Nature. 1996 Mar 14;380(6570):171-5 [8600394] Genes Dev. 1996 Jul 1;10(13):1670-82 [8682297] Nature. 1996 Sep 12;383(6596):168-72 [8774881] Exp Cell Res. 1996 Nov 25;229(1):1-6 [8940242] Br J Cancer. 1997;75(1):47-53 [9000597] Nat Genet. 1997 Feb;15(2):207-11 [9020852] Cancer Lett. 1996 Dec 3;109(1-2):91-9 [9020907] J Cell Biol. 1997 Jun 30;137(7):1663-81 [9199179] Development. 1997 Jul;124(13):2659-70 [9217007] J Cell Sci. 1998 Feb;111 ( Pt 3):347-57 [9427683] Cell. 1998 Mar 20;92(6):797-808 [9529255] Genes Dev. 1998 Jun 1;12(11):1587-92 [9620846] Nature. 1998 Jun 25;393(6687):786-90 [9655392] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9378-83 [9689088] Cell. 1998 Sep 18;94(6):703-14 [9753318] Hepatology. 1998 Oct;28(4):1095-104 [9755248] Annu Rev Biochem. 1998;67:753-91 [9759503] Oncogene. 1998 Sep 17;17(11 Reviews):1395-413 [9779987] Nat Cell Biol. 1999 Dec;1(8):472-8 [10587642] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender Differences in Personality Traits across Cultures: Robust and Surprising Findings AN - 60428600; 200217602 AB - Secondary analyses of Revised NEO Personality Inventory data from 26 cultures (N = 23,031) suggest that gender differences are small relative to individual variation within genders; differences are replicated across cultures for both college-age & adult samples, & differences are broadly consistent with gender stereotypes: Women reported themselves to be higher in Neuroticism, Agreeableness, Warmth, & Openness to Feelings, whereas men were higher in Assertiveness & Openness to Ideas. Contrary to predictions from evolutionary theory, the magnitude of gender differences varied across cultures. Contrary to predictions from the social role model, gender differences were most pronounced in European & American cultures in which traditional sex roles are minimized. Possible explanations for this surprising finding are discussed, including the attribution of masculine & feminine behaviors to roles rather than traits in traditional cultures. 3 Tables, 61 References. [Copyright 2001 The American Psychological Association.] JF - Journal of Personality and Social Psychology AU - Costa, Paul T, Jr AU - Terracciano, Antonio AU - McCrae, Robert R AD - Laboratory Personality & Cognition, Gerontology Resesarch Center, National Instit Aging, National Instits Health, Baltimore, MD e-mail:paulc@lpc.grc.nia.nih.gov Y1 - 2001/08// PY - 2001 DA - August 2001 SP - 322 EP - 331 VL - 81 IS - 2 SN - 0022-3514, 0022-3514 KW - Personality Traits KW - Self Evaluation KW - Individual Differences KW - Sex Role Orientations KW - Sex Differences KW - Evolutionary Theories KW - Crosscultural Differences KW - Sex Stereotypes KW - article KW - 2983: feminist/gender studies; sociology of gender & gender relations KW - 0312: social psychology; personality & social roles (individual traits, social identity, adjustment, conformism, & deviance) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60428600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Personality+and+Social+Psychology&rft.atitle=Gender+Differences+in+Personality+Traits+across+Cultures%3A+Robust+and+Surprising+Findings&rft.au=Costa%2C+Paul+T%2C+Jr%3BTerracciano%2C+Antonio%3BMcCrae%2C+Robert+R&rft.aulast=Costa&rft.aufirst=Paul&rft.date=2001-08-01&rft.volume=81&rft.issue=2&rft.spage=322&rft.isbn=&rft.btitle=&rft.title=Journal+of+Personality+and+Social+Psychology&rft.issn=00223514&rft_id=info:doi/10.1037%2F%2F0022-3514.81.2.322 LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JPSPB2 N1 - SubjectsTermNotLitGenreText - Sex Differences; Personality Traits; Crosscultural Differences; Individual Differences; Sex Stereotypes; Self Evaluation; Evolutionary Theories; Sex Role Orientations DO - http://dx.doi.org/10.1037//0022-3514.81.2.322 ER - TY - JOUR T1 - Osmotically Responsive Genes: The Mammalian Osmotic Response Element (ORE) AN - 19830349; 5668824 AB - Evolutionarily, adaptation to hyperosmotic stress through accumulation of osmotically active organic solutes (organic osmolytes) is a highly conserved mechanism. Hyperosmotic accumulation of organic osmolytes is transcriptionally regulated: e.g. , betaine in bacteria (e.g. , Escherichia coli), glycerol in yeast (e.g. , Saccharomyces cerevisiae), betaine in plants (e.g. , Spinacea oleracea L.) and sorbitol, betaine, and inositol in cells of the mammalian renal medulla. Renal medullary cells, among mammalian cells, are uniquely exposed to hyperosmotic stress; in these cells, hyperosmotic stress results in accumulation of sorbitol as one of the predominant osmolytes. Sorbitol accumulates due to a rise in the synthesis rate of aldose reductase (AR), which catalyzes the conversion of glucose to sorbitol. Hyperosmotic stress increases transcription of the AR gene which leads to a rise in AR mRNA levels. In cloning and characterizing the rabbit AR gene, the first evidence of a eukaryotic osmotic response element (ORE) was found. Since then, several mammalian OREs (also called TonE) have been discovered. Sequence containing an ORE was identified for the canine Na+- and Cl--coupled betaine transporter gene as well as the Na+/myo-inositol cotransporter gene. Because it is possible to find homology between the OREs of the AR genes and those of the betaine and inositol genes, a consensus for the mammalian ORE was derived by functional assessment. Most recent studies have resulted in the discovery of other cis-elements that potentiate the ORE response and a trans-activating factor that binds to the ORE. JF - American Zoologist AU - Ferraris, J D AU - GarcIa-Perez, A AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart Lung Blood Institute, National Institutes of Health, 10 Center Dr-MSC 1603, Bethesda, Maryland 20892-1603, jdf@helix.nih.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 734 EP - 742 PB - The Society for Integrative and Comparative Biology VL - 41 IS - 4 SN - 0003-1569, 0003-1569 KW - Genetics Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Adaptations KW - Regulatory sequences KW - Inositol KW - Glucose KW - Transcription KW - Stress KW - Sorbitol KW - Betaine KW - Saccharomyces cerevisiae KW - Solutes KW - Glycerol KW - Ores KW - Mammalian cells KW - Homology KW - Escherichia coli KW - Aldehyde reductase KW - Kidney KW - Spinacia oleracea KW - Evolution KW - J 02410:Animal Diseases KW - K 03310:Genetics & Taxonomy KW - G 07700:Molecular Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19830349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Zoologist&rft.atitle=Osmotically+Responsive+Genes%3A+The+Mammalian+Osmotic+Response+Element+%28ORE%29&rft.au=Ferraris%2C+J+D%3BGarcIa-Perez%2C+A&rft.aulast=Ferraris&rft.aufirst=J&rft.date=2001-08-01&rft.volume=41&rft.issue=4&rft.spage=734&rft.isbn=&rft.btitle=&rft.title=American+Zoologist&rft.issn=00031569&rft_id=info:doi/10.1043%2F0003-1569%282001%29041%280734%3AORGTMO%292.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-1569&volume=41&page=734 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Adaptations; Regulatory sequences; Inositol; Glucose; Stress; Transcription; Sorbitol; Betaine; Solutes; Glycerol; Homology; Mammalian cells; Ores; Kidney; Aldehyde reductase; Evolution; Escherichia coli; Spinacia oleracea; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1043/0003-1569(2001)041(0734:ORGTMO)2.0.CO;2 ER - TY - JOUR T1 - Mortality after Cerebral Angiography with or without Radioactive Thorotrast: An International Cohort of 3,143 Two-Year Survivors AN - 19618777; 8693218 AB - Travis, L. B., Land, C. E., Andersson, M., Nyberg, U., Goldman, M. B., Knudson Gaul, L., Berger, E., Storm, H. H., Hall, P., Auvinen, A., Janower, M. L., Holm, L-E., Monson, R. R., Schottenfeld D. and Boice, J. D., Jr. Mortality after Cerebral Angiography with or without Radioactive Thorotrast: An International Cohort of 3,143 Two-Year Survivors. Radiat. Res. 156, 136-150 (2001). There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P 20 ml Thorotrast and approached 50%. JF - Radiation Research AU - Travis, Lois B AU - Land, Charles E AU - Andersson, Michael AU - Nyberg, Ullakarin AU - Goldman, Marlene B AU - Knudson Gaul, Linda AU - Berger, Eric AU - Storm, Hans H AU - Hall, Per AU - Auvinen, Anssi AU - Janower, Murray L AU - Holm, Lars-Erik AU - Monson, Richard R AU - Schottenfeld, David AU - Boice, John D, Jr AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892, travisl@epndce.nci.nih.gov. Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 136 EP - 150 PB - Allen Press, Inc., 810 East Tenth St. VL - 156 IS - 2 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Risk assessment KW - Mortality KW - Liver diseases KW - Mathematical models KW - Complications KW - Liver cancer KW - Tumors KW - Cancer KW - Blood KW - Angiography KW - Radiation KW - Contrast media KW - Radioisotopes KW - Hematological diseases KW - Benign KW - X 24390:Radioactive Materials KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19618777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+Research&rft.atitle=Mortality+after+Cerebral+Angiography+with+or+without+Radioactive+Thorotrast%3A+An+International+Cohort+of+3%2C143+Two-Year+Survivors&rft.au=Travis%2C+Lois+B%3BLand%2C+Charles+E%3BAndersson%2C+Michael%3BNyberg%2C+Ullakarin%3BGoldman%2C+Marlene+B%3BKnudson+Gaul%2C+Linda%3BBerger%2C+Eric%3BStorm%2C+Hans+H%3BHall%2C+Per%3BAuvinen%2C+Anssi%3BJanower%2C+Murray+L%3BHolm%2C+Lars-Erik%3BMonson%2C+Richard+R%3BSchottenfeld%2C+David%3BBoice%2C+John+D%2C+Jr&rft.aulast=Travis&rft.aufirst=Lois&rft.date=2001-08-01&rft.volume=156&rft.issue=2&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1667%2F0033-7587%282001%291562.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Risk assessment; Mortality; Mathematical models; Liver diseases; Complications; Liver cancer; Tumors; Cancer; Blood; Angiography; Radiation; Radioisotopes; Contrast media; Hematological diseases; Benign DO - http://dx.doi.org/10.1667/0033-7587(2001)156[0136:MACAWO]2.0.CO;2 ER - TY - JOUR T1 - Adoptive Transfer of Cloned Melanoma-Reactive T Lymphocytes for the Treatment of Patients with Metastatic Melanoma AN - 18414175; 5395145 AB - This report describes a phase I study of the adoptive transfer of cloned melanoma antigen-specific T lymphocytes for therapy of patients with advanced melanoma. Clones were derived from peripheral blood lymphocytes or tumor-infiltrating lymphocytes of patients who had received prior immunization with the melanoma-associated antigen, gp100. In response to its cognate antigen, each clone used for treatment secreted large amounts of interferon- gamma and granulocyte-macrophage colony-stimulating factor, lesser amounts of interleukin (IL)-2 and tumor necrosis factor- alpha , and little or no IL-4 and IL-10. Clones also demonstrated recognition of human leukocyte antigen-matched melanomas using cytokine secretion and lysis assays. Twelve patients received 2 cycles of cells alone; 11 patients received additional cycles of cells and were randomized between two schedules of IL-2 (125,000 IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg intravenously every 8 h for 4 days). A total of 51 cycles of cells were administered, with an average of 1 x 10 super(10) cells per cycle. Peripheral blood samples were analyzed for persistence of transferred cells by T-cell receptor-specific polymerase chain reaction. Transferred cells reached a maximum level at 1 h after transfer but rapidly declined to undetectable levels by 2 weeks. One minor response and one mixed response were observed (both in the high-dose IL-2 arm). This report demonstrates the safety and feasibility of cloned T-cell transfer as a therapy for patients with cancer. The lack of clinical effectiveness of this protocol suggests that transfer of different or additional cell types or that modulation of the recipient host environment is required for successful therapy. JF - Journal of Immunotherapy AU - Dudley, ME AU - Wunderlich, J AU - Nishimura, MI AU - Yu, D AU - Yang, J C AU - Topalian, S L AU - Schwartzentruber, D J AU - Hwu, P AU - Marincola, F M AU - Sherry, R AU - Leitman, S F AU - Rosenberg, SA AD - Surgery Branch, National Cancer Institute, Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 363 EP - 373 VL - 24 IS - 4 SN - 1067-5582, 1067-5582 KW - glycoprotein gp100 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06818:Cancer immunotherapy KW - F 06756:Function KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18414175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy&rft.atitle=Adoptive+Transfer+of+Cloned+Melanoma-Reactive+T+Lymphocytes+for+the+Treatment+of+Patients+with+Metastatic+Melanoma&rft.au=Dudley%2C+ME%3BWunderlich%2C+J%3BNishimura%2C+MI%3BYu%2C+D%3BYang%2C+J+C%3BTopalian%2C+S+L%3BSchwartzentruber%2C+D+J%3BHwu%2C+P%3BMarincola%2C+F+M%3BSherry%2C+R%3BLeitman%2C+S+F%3BRosenberg%2C+SA&rft.aulast=Dudley&rft.aufirst=ME&rft.date=2001-08-01&rft.volume=24&rft.issue=4&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Adenovirus-Mediated MUC1 Gene Transduction into Human Blood-Derived Dendritic Cells AN - 18413199; 5395143 AB - MUC1 protein is widely expressed on various human cancer cells and has a specific highly glycosylated core structure with multiple tandem repeats, which may include an immunogenic peptide sequence. The potency of MUC1 protein to induce human histocompatibility leukocyte antigen-class I-restricted cytotoxic T-lymphocyte (CTL) induction remains to be fully clarified in human beings. In the current study, we made MUC1-expressing human dendritic cells (DCs) using recombinant adenovirus vector. Adenovirus vector plasmid containing human MUC1 cDNA, pAdHM4-MUC1 was constructed using in vitro ligation with a shuttle vector, pHMCMV5. Adenovirus vector expressing MUC1 was generated by the transfection of Pac I-digested recombinant vector plasmid into 293 cells. Human blood DCs were obtained from 7-day culture of monocytes with recombinant human (rh) granulocyte-macrophage (GM) colony-stimulating factor (CSF) and (rh)interleukin (IL)-4. Then, 1 x 10 super(6) DCs were incubated with viral supernatant at a multiplicity of infection of 200 for 24 h in the presence of rhGM-CSF and rhIL-4. Flow cytometric analysis showed that 30% to 40% of the transduced DCs expressed MUC1 protein; by contrast, nontransduced or transduced DCs with mock virus expressed only small amounts of MUC1 protein. Adenovirus-mediated MUC1 gene transduction into DCs had no significant effect on DC surface marker expressions or functions such as mixed leukocyte reaction. Furthermore, MUC1-specific CD8 super(+) CTLs could be induced from healthy donor blood lymphocytes using MUC1-expressing DCs as stimulators. These results suggested that MUC1 gene-transduced DCs are a functional and potent tool for triggering a CTL response against MUC1 super(+) cancer cells. JF - Journal of Immunotherapy AU - Maruyama, K AU - Akiyama, Y AU - Nara-Ashizawa, N AU - Hojo, T AU - Cheng, J-Y AU - Mizuguchi, H AU - Hayakawa, T AU - Yamaguchi, K AD - Growth Factor Division, National Cancer Center Research Institute, Division of Biological Chemistry and Biologicals, National Institutes of Health Sciences, Tokyo, Japan Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 345 EP - 353 VL - 24 IS - 4 SN - 1067-5582, 1067-5582 KW - MUC-1 antigen KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33181:Gene therapy vectors KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18413199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy&rft.atitle=Adenovirus-Mediated+MUC1+Gene+Transduction+into+Human+Blood-Derived+Dendritic+Cells&rft.au=Maruyama%2C+K%3BAkiyama%2C+Y%3BNara-Ashizawa%2C+N%3BHojo%2C+T%3BCheng%2C+J-Y%3BMizuguchi%2C+H%3BHayakawa%2C+T%3BYamaguchi%2C+K&rft.aulast=Maruyama&rft.aufirst=K&rft.date=2001-08-01&rft.volume=24&rft.issue=4&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - How do thermophilic proteins deal with heat? AN - 18221577; 5280250 AB - Recent years have witnessed an explosion of sequence and structural information for proteins from hyperthermophilic and thermophilic organisms. Complete genome sequences are available for many hyperthermophilic archaeons. Here, we review some recent studies on protein thermostability along with work from our laboratory. A large number of sequence and structural factors are thought to contribute toward higher intrinsic thermal stability of proteins from these organisms. The most consistent are surface loop deletion, increased occurrence of hydrophobic residues with branched side chains and an increased proportion of charged residues at the expense of uncharged polar residues. The energetic contribution of electrostatic interactions such as salt bridges and their networks toward protein stability can be stabilizing or destabilizing. For hyperthermophilic proteins, the contribution is mostly stabilizing. Macroscopically, improvement in electrostatic interactions and strengthening of hydrophobic cores by branched apolar residues increase the enthalpy change between the folded and unfolded states of a thermophilic protein. At the same time, surface loop deletion contributes to decreased conformational entropy and decreased heat capacity change between the folded and unfolded states of the protein. JF - Cellular and Molecular Life Sciences AU - Kumar, S AU - Nussinov, R AD - Intramural Research Support Program-SAIC, National Cancer Institute-Frederick, Frederick Cancer Research and Development Center, Bldg 469, Rm 151, Frederick, Maryland 21702, USA, ruthn@ncifcrf.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 1216 EP - 1233 VL - 58 IS - 9 SN - 1420-682X, 1420-682X KW - Microbiology Abstracts B: Bacteriology KW - Protein folding KW - Heat tolerance KW - Electrostatic properties KW - Hydrophobicity KW - Thermal stability KW - Thermophilic microorganisms KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18221577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+Molecular+Life+Sciences&rft.atitle=How+do+thermophilic+proteins+deal+with+heat%3F&rft.au=Kumar%2C+S%3BNussinov%2C+R&rft.aulast=Kumar&rft.aufirst=S&rft.date=2001-08-01&rft.volume=58&rft.issue=9&rft.spage=1216&rft.isbn=&rft.btitle=&rft.title=Cellular+and+Molecular+Life+Sciences&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermophilic microorganisms; Thermal stability; Heat tolerance; Hydrophobicity; Electrostatic properties; Protein folding ER - TY - JOUR T1 - Effect of Benzo-Ring Hydroxyl Groups on Site-Specific Mutagenesis by Tetrahydrobenzo[a]pyrene Adducts at N super(6) of Deoxyadenosine AN - 18212075; 5280146 AB - We have previously investigated the mutations induced on replication in Escherichia coli of the M13mp7L2 genome containing each of the eight possible adducts derived from the four optically active 7,8-diol 9,10-epoxide metabolites of benzo[a]pyrene (B[a]P) by alkylation of a specific deoxyadenosine (dAdo) residue at N super(6). Observed mutational frequencies depended in part on the relative spatial orientations of the three hydroxyl groups in these adducts. To determine how the presence or absence of these hydroxyl groups affects mutational response, we have synthesized 16-mer oligonucleotides with the same sequence as one of those previously studied with the diol epoxide adducts, but containing B[a]P-dAdo adducts in which two or all three of the adduct hydroxyl groups were replaced by hydrogen. Transfection of the adducted M13 constructs into SOS-induced Escherichia coli consistently gave fewer infective centers than the control construct, with viabilities ranging from 8.4 to 44.9% relative to control. In general, decreasing the number of adduct hydroxyls decreased the total frequency of substitution mutations induced. For all but one of the present adducts, the total mutational frequency was lower than that for any of the previously reported diol epoxide adducts in the same sequence. Remarkably, this (9S,10R)-adduct with cis orientation of the dAdo residue and the 9-OH group gave the highest mutational frequency of all the B[a]P adducts studied in this sequence, including the diol epoxide adducts. With the present adducts, A arrow right T transversions predominated, with smaller numbers of A arrow right G transitions and even fewer A arrow right C transversions. JF - Chemical Research in Toxicology AU - Ramos, LA AU - Sayer, J M AU - Yagi, H AU - Shah, J H AU - Dipple, A AU - Jerina, D M AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 1082 EP - 1089 VL - 14 IS - 8 SN - 0893-228X, 0893-228X KW - tetrahydrobenzo(a)pyrene KW - Toxicology Abstracts KW - Alkylating agents KW - DNA adducts KW - Polycyclic aromatic hydrocarbons KW - Mutagenicity KW - Deoxyguanosine KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18212075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Effect+of+Benzo-Ring+Hydroxyl+Groups+on+Site-Specific+Mutagenesis+by+Tetrahydrobenzo%5Ba%5Dpyrene+Adducts+at+N+super%286%29+of+Deoxyadenosine&rft.au=Ramos%2C+LA%3BSayer%2C+J+M%3BYagi%2C+H%3BShah%2C+J+H%3BDipple%2C+A%3BJerina%2C+D+M&rft.aulast=Ramos&rft.aufirst=LA&rft.date=2001-08-01&rft.volume=14&rft.issue=8&rft.spage=1082&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Mutagenicity; DNA adducts; Polycyclic aromatic hydrocarbons; Alkylating agents; Deoxyguanosine ER - TY - JOUR T1 - A prospective study on intake of animal products and risk of prostate cancer AN - 18182219; 5180902 AB - Objective: Association between animal products and prostate cancer have been observed in numerous observational studies, but it is not clear whether the high fat content of these foods or some other component accounts for these associations. We examine these associations among 51,529 men who contributed detailed dietary data. Methods: Participants of the Health Professionals Follow-Up Study completed a semiquantitative food-frequency questionnaire in 1986, and subsequently in 1990 and 1994. Other data on potential risk factors were collected at baseline and in subsequent questionnaires during follow-up. Between 1986 and 1996, 1897 total cases of prostate cancer (excluding stage A sub(1)) and 249 metastatic cancers were identified. We used pooled logistic regression for analyses of diet and prostate cancer. Results: Intakes of total meat, red meat, and dairy products were not associated with risk of total or advanced prostate cancer. An elevated risk for metastatic prostate cancer was observed with intake of red meat (relative risk (RR) = 1.6 for top vs. bottom quintile comparison, 95% confidence interval (CI) = 1.0-2.5); this association was slightly attenuated after controlling for saturated and alpha -linolenic fatty acids (RR = 1.5, 95% CI = 0.88-2.5). Processed meats, bacon and beef, pork or lamb as a main dish each contributed to an elevated risk of metastatic prostate cancer. Dairy product intake increased risk of metastatic prostate cancer (RR = 1.4, 95% CI = 0.91-2.2 for top vs. bottom quintile comparison), but no association remained after controlling for calcium and other fatty acids. A high intake in both red meat and dairy product was associated with a statistically significant two-fold elevation in risk of metastatic prostate cancer, compared to low intake of both products; however, most of the excess risk could be explained by known nutritional components of these foods. Conclusions: Intakes of red meat and dairy products appear to be related to increased risk of metastatic prostate cancer. While known nutrients, such as calcium and fatty acids, may explain most of the dairy association observed, it appears that a portion of the risk of metastatic prostate cancer associated with red meat intake remains unexplained. JF - Cancer Causes & Control AU - Michaud, D S AU - Augustsson, K AU - Rimm, E B AU - Stampfer, MJ AU - Willett, W C AU - Giovannucci, E AD - National Cancer Institute, 6120 Executive Blvd, EPS Rm 7026, Rockville, MD 20852, USA, michaudd@mail.nih.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 557 EP - 567 VL - 12 IS - 6 SN - 0957-5243, 0957-5243 KW - fats KW - prostate KW - Risk Abstracts; Health & Safety Science Abstracts KW - Diets KW - Cancer KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18182219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=A+prospective+study+on+intake+of+animal+products+and+risk+of+prostate+cancer&rft.au=Michaud%2C+D+S%3BAugustsson%2C+K%3BRimm%2C+E+B%3BStampfer%2C+MJ%3BWillett%2C+W+C%3BGiovannucci%2C+E&rft.aulast=Michaud&rft.aufirst=D&rft.date=2001-08-01&rft.volume=12&rft.issue=6&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Diets; Cancer ER - TY - JOUR T1 - Using HSV-Thymidine Kinase for Safety in an Allogeneic Salivary Graft Cell Line AN - 18152014; 5175536 AB - Extreme salivary hypofunction is a result of tissue damage caused by irradiation therapy for cancer in the head and neck region. Unfortunately, there is no currently satisfactory treatment for this condition that affects up to 40,000 people in the United States every year. As a novel approach to managing this problem, we are attempting to develop an orally implantable, fluid-secreting device (an artificial salivary gland). We are using the well-studied HSG salivary cell line as a potential allogeneic graft cell for this device. One drawback of using a cell line is the potential for malignant transformation. If such an untoward response occurred, the device could be removed. However, in the event that any HSG cells escaped, we wished to provide additional patient protection. Accordingly, we have engineered HSG cells with a hybrid adeno-retroviral vector, AdLTR.CMV-tk, to express the herpes simplex virus thymidine kinase (HSV-tk) suicide gene as a novel safety factor. Cells were grown on plastic plates or on poly-L-lactic acid disks and then transduced with different multiplicities of infection (MOIs) of the hybrid vector. Thereafter, various concentrations of ganciclovir (GCV) were added, and cell viability was tested. Transduced HSG cells expressed HSV-tk and were sensitive to GCV treatment. Maximal effects were seen at a MOI of 10 with 50 mu M of GCV, achieving 95% cell killing on the poly-L-lactic acid substrate. These results suggest that engineering the expression of a suicide gene in an allogeneic graft cell may provide additional safety for use in an artificial salivary gland device. JF - Tissue Engineering AU - Aframian, D J AU - Zheng, Changyu AU - Goldsmith, C M AU - Nikolovski, J AU - Cukierman, E AU - Yamada, K M AU - Mooney, D J AU - Birkedal-Hansen, H AU - Baum, B J AD - GTTB, NIDCR, NIH, Bldg. 10, Rm 1N113, MSC-1190, Bethesda, MD 20892, USA, bbaum@dir.nidcr.nih.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 405 EP - 413 VL - 7 IS - 4 SN - 1076-3279, 1076-3279 KW - HSV KW - ganciclovir KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Transformation KW - Malignancy KW - Retrovirus KW - Gene therapy KW - Gene transfer KW - Thymidine kinase KW - Salivary gland KW - Herpes simplex virus KW - Cancer KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18152014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tissue+Engineering&rft.atitle=Using+HSV-Thymidine+Kinase+for+Safety+in+an+Allogeneic+Salivary+Graft+Cell+Line&rft.au=Aframian%2C+D+J%3BZheng%2C+Changyu%3BGoldsmith%2C+C+M%3BNikolovski%2C+J%3BCukierman%2C+E%3BYamada%2C+K+M%3BMooney%2C+D+J%3BBirkedal-Hansen%2C+H%3BBaum%2C+B+J&rft.aulast=Aframian&rft.aufirst=D&rft.date=2001-08-01&rft.volume=7&rft.issue=4&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Herpes simplex virus; Cancer; Salivary gland; Transformation; Malignancy; Expression vectors; Thymidine kinase; Gene transfer; Gene therapy; Retrovirus ER - TY - JOUR T1 - The Immature Mouse Is a Suitable Model for Detection of Estrogenicity in the Uterotropic Bioassay AN - 18147148; 5274799 AB - The traditional rodent uterotropic response assay has been incorporated into the U.S. Environmental Protection Agency's screening and testing program for environmental endocrine-disrupting chemicals (EDCs). While much effort continues to focus on determining protocol variables, few studies compare uterotropic responses in rats, a species commonly used in toxicologic testing, with other rodent species. In this study, we compared uterine responses in immature outbred CD-1 mice and Sprague-Dawley rats. After three daily subcutaneous injections with 17 beta -estradiol (0.1-500 mu g/kg/day), immature mice and rats demonstrated a similar dose-response increase in absolute uterine wet weight and uterine weight:body weight ratio. Further, morphologic and biochemical parameters of estrogenicity, including uterine epithelial cell height and number, gland number, and induction of estrogen-responsive proteins lactoferrin and complement C3, mirror wet weight increases. We conclude that mice are as well suited as rats for the uterotropic bioassay. Because of the advantages of using mice, including lower costs, less space required, and smaller amounts of compound needed for tests, mice should be given appropriate consideration in testing paradigms for EDCs JF - Environmental Health Perspectives AU - Padilla-Banks, E AU - Jefferson, W N AU - Newbold, R R AD - NIEHS, MD E4-02, Research Triangle Park, NC 27709, USA, newbold1@niehs.nih.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 821 EP - 826 VL - 109 IS - 8 SN - 0091-6765, 0091-6765 KW - uterotropic response assay KW - mice KW - rats KW - endocrine system KW - Toxicology Abstracts KW - Uterus KW - Bioassays KW - Estrus cycle KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18147148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=The+Immature+Mouse+Is+a+Suitable+Model+for+Detection+of+Estrogenicity+in+the+Uterotropic+Bioassay&rft.au=Padilla-Banks%2C+E%3BJefferson%2C+W+N%3BNewbold%2C+R+R&rft.aulast=Padilla-Banks&rft.aufirst=E&rft.date=2001-08-01&rft.volume=109&rft.issue=8&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioassays; Estrus cycle; Uterus ER - TY - JOUR T1 - Agricultural use of organophosphate pesticides and the risk of non-Hodgkin's lymphoma among male farmers (United States) AN - 18096930; 5180900 AB - Objective: Data from three population-based case-control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkin's lymphoma (NHL) among white male farmers. Methods: The data set included 748 cases of non-Hodgkin's lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression. Results: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures. Conclusions: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted. JF - Cancer Causes & Control AU - Waddell, B L AU - Zahm, SH AU - Baris, D AU - Weisenburger, D D AU - Holmes, F AU - Burmeister, L F AU - Cantor, K P AU - Blair, A AD - National Cancer Institute, EPS Room 8118, Bethesda, MD 20892, USA Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 509 EP - 517 VL - 12 IS - 6 SN - 0957-5243, 0957-5243 KW - man KW - males KW - USA, Iowa KW - USA, Kansas KW - USA, Minnesota KW - USA, Nebraska KW - farming KW - lymphoma KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - Risk assessment KW - Farms KW - Organophosphates KW - Lymphoma KW - Occupational exposure KW - Pesticides (organophosphorus) KW - Agrochemicals KW - Pesticides KW - R2 23080:Industrial and labor KW - H 5000:Pesticides KW - X 24132:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18096930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Agricultural+use+of+organophosphate+pesticides+and+the+risk+of+non-Hodgkin%27s+lymphoma+among+male+farmers+%28United+States%29&rft.au=Waddell%2C+B+L%3BZahm%2C+SH%3BBaris%2C+D%3BWeisenburger%2C+D+D%3BHolmes%2C+F%3BBurmeister%2C+L+F%3BCantor%2C+K+P%3BBlair%2C+A&rft.aulast=Waddell&rft.aufirst=B&rft.date=2001-08-01&rft.volume=12&rft.issue=6&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticides; Organophosphates; Occupational exposure; Agrochemicals; Farms; Pesticides (organophosphorus); Risk assessment; Lymphoma ER - TY - JOUR T1 - Occupation and the risk of laryngeal cancer in Turkey AN - 18093207; 5183938 AB - A hospital-based case-referent study was conducted in Turkey to provide further information on occupational risk factors and laryngeal cancer. Among 7631 cancer cases seen at an oncology treatment center between 1979 and 1984, 958 laryngeal cancer cases were identified among men. Occupational history, tobacco and alcohol use, and demographic data were obtained from patients with a standardized questionnaire. Special 7-digit standard occupational and industrial codes were created to classify the job and industrial titles of the subjects. After exclusions, 940 laryngeal cancer cases and 1519 referents were available for study. Age-, smoking- and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Excess laryngeal cancer occurred among guards (OR 1.5, 95% CI 1.1-2.1), production supervisors (OR 1.8, 95% CI 1.1-3.1), textile workers (OR 1.9, 95% CI 1.2-3.3), drivers (OR 1.7, 95% CI 1.1-2.4), construction workers (OR 1.7, 95% CI 1.2-2.6), and workers in grain mills (OR 3.1, 95% CI: 1.3-7.6), trade unions (OR 3.6, 95% CI: 1.1-11.7) and local government services (OR 4.7, 95% CI 1.7-12.5). Supraglottic cancer was excessive among the textile workers, construction workers, and local government laborers, all with potential dust exposure. The risks of the general managers, electricians, and workers from industries such as pharmaceutical production, industrial machinery production, electric utilities, and retail services were lower than expected. The risk of laryngeal cancer was associated with several occupations, and supraglottic larynx cancer appears to be more common among workers in dusty occupations and industries. JF - Scandinavian Journal of Work, Environment & Health AU - Elci, O C AU - Dosemeci, M AU - Blair, A AD - Occupational Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, EPS 8111, MSC 7240, Rockville, MD 20852-7240, USA, elcio@mail.nih.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 233 EP - 239 VL - 27 IS - 4 SN - 0355-3140, 0355-3140 KW - Turkey KW - larynx KW - Risk Abstracts; Health & Safety Science Abstracts KW - Cancer KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18093207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Occupation+and+the+risk+of+laryngeal+cancer+in+Turkey&rft.au=Elci%2C+O+C%3BDosemeci%2C+M%3BBlair%2C+A&rft.aulast=Elci&rft.aufirst=O&rft.date=2001-08-01&rft.volume=27&rft.issue=4&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Cancer ER - TY - JOUR T1 - Benzene and lymphohematopoietic malignancies in humans AN - 18083367; 5166610 AB - Background: Quantitative evaluations of benzene-associated risk for cancer have relied primarily on findings from a cohort study of highly exposed U.S. rubber workers. An epidemiologic investigation in China (NCI/CAPM study) extended quantitative evaluations of cancer risk to a broader range of benzene exposures, particularly at lower levels. Methods: We review the evidence implicating benzene in the etiology of hematopoietic disorders, clarify methodologic aspects of the NCI/CAPM study, and examine the study in the context of the broader literature on health effects associated with occupational benzene exposure. Results: Quantitative relationships for cancer risk from China and the U.S. show a relatively smooth increase in risk for acute myeloid leukemia and related conditions over a broad dose range of benzene exposure (below 200 ppm-years mostly from the China study and above 200 ppm-years mostly from the U.S. study). Conclusions: Risks of acute myeloid leukemia and other malignant and nonmalignant hematopoietic disorders associated with benzene exposure in China are consistent with other information about benzene exposure, hematotoxicity, and cancer risk, extending evidence for hematopoietic cancer risks to levels substantially lower than had previously been established. JF - American Journal of Industrial Medicine AU - Hayes, R B AU - Songnian, Y AU - Dosemeci, M AU - Linet, M AD - Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, Maryland 20892, USA, hayesr@mail.nih.gov Y1 - 2001/08// PY - 2001 DA - Aug 2001 SP - 117 EP - 126 VL - 40 IS - 2 SN - 0271-3586, 0271-3586 KW - man KW - acute myeloid leukemia KW - hematological diseases KW - leukemogenesis KW - Toxicology Abstracts; Health & Safety Science Abstracts; Risk Abstracts KW - Risk assessment KW - Acute myeloid leukemia KW - Leukemogenesis KW - benzene KW - Benzene KW - Hematological diseases KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18083367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Benzene+and+lymphohematopoietic+malignancies+in+humans&rft.au=Hayes%2C+R+B%3BSongnian%2C+Y%3BDosemeci%2C+M%3BLinet%2C+M&rft.aulast=Hayes&rft.aufirst=R&rft.date=2001-08-01&rft.volume=40&rft.issue=2&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Risk assessment; benzene; Benzene; Hematological diseases; Leukemogenesis; Acute myeloid leukemia ER - TY - JOUR T1 - Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia AN - 17905223; 5164948 AB - Calcitonin precursor (CTpr) levels are both markers and mediators of inflammation. The duration of their elevation after intravenous endotoxin challenge and the effects of anti-inflammatory therapies were studied in 52 subjects. CTpr levels maximized at 24 h in all subjects. At 7 days (n = 4), after levels of acute-phase cytokines and C-reactive protein had normalized, CTpr levels remained 2-4-fold above baseline levels. The elimination half-life of CTpr levels ranged from 26.9 to 45.7 h. At 24 h, endotoxin and ibuprofen (compared with endotoxin alone) increased CTpr levels approximately 2-fold (P = .03), whereas soluble tumor necrosis factor receptor blunted the increase in CTpr levels by 2-3-fold (P = .0015). However, soluble interleukin-1 receptor failed to alter the increase in CTpr levels. Thus, the fact that anti-inflammatory agents may alter CTpr levels resulting from a single stimulus must be considered when CTpr is used as a clinical marker. Of importance, this study reveals that anti-inflammatory agents may modulate the CTpr level, which is a potential toxic mediator of inflammation. JF - Journal of Infectious Diseases AU - Preas, HL II AU - Nylen, E S AU - Snider, R H AU - Becker, K L AU - White, J C AU - Agosti, J M AU - Suffredini, A F AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2001/08/01/ PY - 2001 DA - 2001 Aug 01 SP - 373 EP - 376 VL - 184 IS - 3 SN - 0022-1899, 0022-1899 KW - man KW - Calcitonin precursor KW - ibuprofen KW - tumor necrosis factor receptors KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Serum levels KW - Endotoxins KW - Calcitonin KW - Tumor necrosis factor KW - Interleukin 1 KW - Endotoxemia KW - Antiinflammatory agents KW - Inflammation KW - J 02855:Human Bacteriology: Others KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Effects+of+anti-inflammatory+agents+on+serum+levels+of+calcitonin+precursors+during+human+experimental+endotoxemia&rft.au=Preas%2C+HL+II%3BNylen%2C+E+S%3BSnider%2C+R+H%3BBecker%2C+K+L%3BWhite%2C+J+C%3BAgosti%2C+J+M%3BSuffredini%2C+A+F&rft.aulast=Preas&rft.aufirst=HL&rft.date=2001-08-01&rft.volume=184&rft.issue=3&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antiinflammatory agents; Inflammation; Endotoxins; Endotoxemia; Calcitonin; Serum levels; Interleukin 1; Tumor necrosis factor ER - TY - JOUR T1 - Conditional epidermal expression of TGFbeta 1 blocks neonatal lethality but causes a reversible hyperplasia and alopecia. AN - 71049975; 11481479 AB - To study the role of transforming growth factor type beta1 (TGFbeta1) in epidermal growth control and disease, we have generated a conditional expression system by using the bovine keratin 5 promoter to drive expression of the tetracycline-regulated transactivators tTA and rTA, and a constitutively active mutant of TGFbeta1 linked to the tetO target sequence for the transactivator. This model allows for induction or suppression of exogenous TGFbeta1 with oral doxycycline. Maximal expression of TGFbeta1 during gestation caused embryonic lethality, whereas partial suppression allowed full-term development with neonatal lethality characterized by runting, epidermal hypoproliferation, and blocked hair follicle growth. With complete suppression, phenotypically normal double transgenic (DT) mice were born. Acute induction of TGFbeta1 in the epidermis of adult mice inhibited basal and follicular keratinocyte proliferation and reentry of telogen hair follicles into anagen. However, chronic expression of TGFbeta1 in adult DTs caused severe alopecia characterized by epidermal and follicular hyperproliferation, apoptosis, as well as dermal fibrosis and inflammation. Readministration of doxycycline to tTA DT mice caused hair regrowth within 14 days. The mRNA and protein for Smad7, an inhibitor of TGFbeta signaling, were up-regulated in the epidermis and hair follicles of alopecic skin and rapidly induced in rTA mice in parallel with the TGFbeta1 transgene, suggesting that the hyperproliferative phenotype may result in part from development of a sustained negative feedback loop. Thus, this conditional expression system provides an important model for understanding the role of TGFbeta1 during development, in normal skin biology, and in disease. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Liu, X AU - Alexander, V AU - Vijayachandra, K AU - Bhogte, E AU - Diamond, I AU - Glick, A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001/07/31/ PY - 2001 DA - 2001 Jul 31 SP - 9139 EP - 9144 VL - 98 IS - 16 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Smad7 Protein KW - Smad7 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Doxycycline KW - N12000U13O KW - Index Medicus KW - Animals KW - Base Sequence KW - Apoptosis -- genetics KW - Trans-Activators -- biosynthesis KW - Doxycycline -- pharmacology KW - DNA-Binding Proteins -- biosynthesis KW - Mice KW - Keratinocytes -- metabolism KW - Cell Division -- genetics KW - Animals, Newborn KW - Hyperplasia -- genetics KW - Alopecia -- genetics KW - Hyperplasia -- prevention & control KW - Transforming Growth Factor beta -- genetics KW - Genes, Lethal KW - Alopecia -- prevention & control KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71049975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Conditional+epidermal+expression+of+TGFbeta+1+blocks+neonatal+lethality+but+causes+a+reversible+hyperplasia+and+alopecia.&rft.au=Liu%2C+X%3BAlexander%2C+V%3BVijayachandra%2C+K%3BBhogte%2C+E%3BDiamond%2C+I%3BGlick%2C+A&rft.aulast=Liu&rft.aufirst=X&rft.date=2001-07-31&rft.volume=98&rft.issue=16&rft.spage=9139&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-08-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Cell Biol. 1999 Sep;1(5):260-6 [10559937] J Cell Biol. 1996 Oct;135(1):227-39 [8858176] FASEB J. 2000 Apr;14(5):752-60 [10744631] Curr Biol. 2000 May 4;10(9):535-8 [10801443] Wound Repair Regen. 2000 Mar-Apr;8(2):128-37 [10810039] J Invest Dermatol. 2000 Nov;115(5):788-94 [11069615] Oncogene. 2001 Jan 25;20(4):471-83 [11313978] Oncogene. 2001 Feb 15;20(7):879-84 [11314022] Nature. 1988 Jan 28;331(6154):363-5 [3422343] EMBO J. 1992 Apr;11(4):1599-605 [1314170] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547-51 [1319065] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5237-41 [7685120] Skin Pharmacol. 1993;6(2):125-34 [8352950] Differentiation. 1994 Jan;55(2):127-36 [8143930] J Invest Dermatol. 1997 Oct;109(4):518-26 [9326384] Nature. 1997 Oct 9;389(6651):631-5 [9335507] Am J Pathol. 1997 Dec;151(6):1601-17 [9403711] Oncogene. 1998 Jul 9;17(1):25-34 [9671311] Annu Rev Biochem. 1998;67:753-91 [9759503] Nature. 1999 Feb 25;397(6721):710-3 [10067896] Cancer Res. 1999 Jun 15;59(12):2861-8 [10383147] Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8483-8 [10411901] Ann Plast Surg. 1999 Aug;43(2):179-84 [10454326] J Dermatol Sci. 1999 Sep;21(1):13-22 [10468187] EMBO J. 1999 Oct 1;18(19):5205-15 [10508154] Anal Biochem. 1994 Feb 1;216(2):276-84 [8179182] J Biol Chem. 1994 Aug 12;269(32):20489-96 [7519609] Genes Dev. 1994 Oct 15;8(20):2429-40 [7958907] Differentiation. 1994 Nov;58(1):53-64 [7532601] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2572-6 [7708687] Genes Dev. 1995 Apr 15;9(8):945-55 [7774812] Teratog Carcinog Mutagen. 1995;15(1):11-21 [7604388] Methods Enzymol. 1995;254:3-20 [8531694] Cell Growth Differ. 1996 May;7(5):679-87 [8732677] Cell. 1996 Aug 23;86(4):531-42 [8752208] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10933-8 [8855286] Genes Dev. 2000 Jan 15;14(2):187-97 [10652273] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the native quaternary structure of vanilloid receptor 1. AN - 71054928; 11358970 AB - Vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that can be activated by capsaicin and other vanilloids as well as by protons and heat. In the present study, we have analyzed the oligomeric state of VR1. Co-immunoprecipitation of differently tagged VR1 molecules indicated that VR1 can form oligomers. Using two different heterologous VR1 expression systems as well as endogenous VR1 expressed in dorsal root ganglion cells, we analyzed oligomer formation using perfluoro-octanoic acid polyacrylamide gel electrophoresis. Results were confirmed both with chemical cross-linking agents as well as through endogenous cross-linking mediated by transglutaminase. Our results clearly show that VR1 forms multimers in each of the expression systems with a homotetramer as a predominant form. The oligomeric structure of VR1 may contribute to the complexity of VR1 pharmacology. Finally, differences in glycosylation between the systems were observed, indicating the need for caution in the use of the heterologous expression systems for analysis of VR1 properties. JF - The Journal of biological chemistry AU - Kedei, N AU - Szabo, T AU - Lile, J D AU - Treanor, J J AU - Olah, Z AU - Iadarola, M J AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/07/27/ PY - 2001 DA - 2001 Jul 27 SP - 28613 EP - 28619 VL - 276 IS - 30 SN - 0021-9258, 0021-9258 KW - Caprylates KW - 0 KW - Cross-Linking Reagents KW - Fluorocarbons KW - Ligands KW - Luminescent Proteins KW - Protons KW - Receptors, Drug KW - Recombinant Fusion Proteins KW - TRPV Cation Channels KW - TRPV1 receptor KW - Green Fluorescent Proteins KW - 147336-22-9 KW - perfluorooctanoic acid KW - 947VD76D3L KW - Transglutaminases KW - EC 2.3.2.13 KW - Index Medicus KW - Fluorocarbons -- chemistry KW - Animals KW - Plasmids -- metabolism KW - COS Cells KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Cross-Linking Reagents -- pharmacology KW - Dimerization KW - Luminescent Proteins -- metabolism KW - Precipitin Tests KW - Protein Structure, Quaternary KW - Recombinant Fusion Proteins -- metabolism KW - Blotting, Western KW - Caprylates -- chemistry KW - Transglutaminases -- metabolism KW - Transfection KW - CHO Cells KW - Cricetinae KW - Receptors, Drug -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71054928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Analysis+of+the+native+quaternary+structure+of+vanilloid+receptor+1.&rft.au=Kedei%2C+N%3BSzabo%2C+T%3BLile%2C+J+D%3BTreanor%2C+J+J%3BOlah%2C+Z%3BIadarola%2C+M+J%3BBlumberg%2C+P+M&rft.aulast=Kedei&rft.aufirst=N&rft.date=2001-07-27&rft.volume=276&rft.issue=30&rft.spage=28613&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-07-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Protective role for c-Jun in the cellular response to DNA damage. AN - 71023324; 11352915 AB - c-Jun, a member of the activation protein 1 (AP-1) family of transcription factors, has been implicated in the regulation of many important biological processes including cell cycle progression, transformation, differentiation, and apoptosis. Accordingly, its expression and function are upregulated in response to diverse stimuli including mitogens and a wide range of stresses. Transcriptional activation of the c-Jun protein is dependent on its phosphorylation at Ser-63 and Ser-73, a process mediated by c-Jun N-terminal kinase. Active c-Jun is required for AP-1 transactivation and c-Jun-mediated transformation, but its role during stress remains unclear as both pro-apoptotic and pro-survival effects of c-Jun have been observed. Here we investigated the importance of c-Jun N-terminal phosphorylation in influencing the sensitivity of human T98G glioblastoma cells to a variety of cytotoxic agents. Stable expression of a nonphosphorylatable dominant negative protein c-Jun(S63A,S73A) markedly inhibited the activation of AP-1-driven transcription and greatly increased the cytotoxic effects of DNA-damaging agents associated with enhanced apoptosis. However, the same cells expressing the mutant Jun protein did not differ from parental cells in their sensitivity to several non-DNA-damaging cytotoxic agents. Our results suggest that activated c-Jun has a selective role in protecting human tumor cells from apoptosis induced by DNA damage. JF - The Journal of biological chemistry AU - Potapova, O AU - Basu, S AU - Mercola, D AU - Holbrook, N J AD - Cell Stress and Aging Section, Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 2001/07/27/ PY - 2001 DA - 2001 Jul 27 SP - 28546 EP - 28553 VL - 276 IS - 30 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Mutagens KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Serine KW - 452VLY9402 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Apoptosis KW - Transcription Factor AP-1 -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Transcription, Genetic KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Transcriptional Activation KW - Serine -- chemistry KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Cisplatin -- pharmacology KW - Flow Cytometry KW - Time Factors KW - Antineoplastic Agents -- pharmacology KW - Stress, Physiological KW - Proto-Oncogene Proteins c-jun -- physiology KW - DNA Damage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71023324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Protective+role+for+c-Jun+in+the+cellular+response+to+DNA+damage.&rft.au=Potapova%2C+O%3BBasu%2C+S%3BMercola%2C+D%3BHolbrook%2C+N+J&rft.aulast=Potapova&rft.aufirst=O&rft.date=2001-07-27&rft.volume=276&rft.issue=30&rft.spage=28546&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surviving starvation AN - 17911494; 5152333 AB - Cells engage in a delicate tightrope act: They must balance energy-efficient growth with the ability to adapt rapidly to sudden changes in their environment. For example, in an environment rich in amino acids, cells do not expend energy making enzymes required for amino acid synthesis. However, if the environment becomes depleted of amino acids (nutritional downshift), cells will be caught lacking both the enzymes required to make amino acids and the amino acids required to make these enzymes. To solve this dilemma, cells in nutrient-poor environments must use their own proteins as sources of amino acids. Once amino acid biosynthetic enzymes start to accumulate, the cell is able to produce its own amino acids, and a new growth phase begins. On page 705 of this issue, Kuroda et al. describe the molecular components that enable cells to adapt to an environmental downshift, when a period of feast abruptly ends and leaner times roll around. JF - Science (Washington) AU - Gottesman, S AU - Maurizi, M R AD - Laboratory of Mol. Biol. and Lab. Cell Biol., Natl. Cancer Inst., Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2001/07/27/ PY - 2001 DA - 2001 Jul 27 SP - 614 EP - 615 PB - American Association for the Advancement of Science VL - 293 IS - 5530 SN - 0036-8075, 0036-8075 KW - bacteria KW - Microbiology Abstracts B: Bacteriology KW - Starvation KW - Amino acids KW - Environmental effects KW - Enzymes KW - Proteins KW - Nutrition KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17911494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Surviving+starvation&rft.au=Gottesman%2C+S%3BMaurizi%2C+M+R&rft.aulast=Gottesman&rft.aufirst=S&rft.date=2001-07-27&rft.volume=293&rft.issue=5530&rft.spage=614&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Proteins; Nutrition; Enzymes; Amino acids; Environmental effects; Starvation ER - TY - JOUR T1 - Interaction of Escherichia coli MutS and MutL at a DNA Mismatch AN - 17896477; 5146308 AB - MutS and MutL are both required to activate downstream events in DNA mismatch repair. We examined the rate of dissociation of MutS from a mismatch using linear heteroduplex DNAs or heteroduplexes blocked at one or both ends by four-way DNA junctions in the presence and absence of MutL. In the presence of ATP, dissociation of MutS from linear heteroduplexes or heteroduplexes blocked at only one end occurs within 15 s. When both duplex ends are blocked, MutS remains associated with the DNA in complexes with half-lives of 30 min. DNase I footprinting of MutS complexes is consistent with migration of MutS throughout the DNA duplex region. When MutL is present, it associates with MutS and prevents ATP-dependent migration away from the mismatch in a manner that is dependent on the length of the heteroduplex. The rate and extent of mismatch-provoked cleavage at hemimethylated GATC sites by MutH in the presence of MutS, MutL, and ATP are the same whether the mismatch and GATC sites are in cis or in trans. These results suggest that a MutS-MutL complex in the vicinity of a mismatch is involved in activating MutH. JF - Journal of Biological Chemistry AU - Schofield, MJ AU - Nayak, S AU - Scott, TH AU - Du, C AU - Hsieh, P AD - Genetics and Biochemistry Branch, NIDDKD, National Institutes of Health, Bethesda, Maryland 20892, USA, hsieh@ncifcrf.gov Y1 - 2001/07/27/ PY - 2001 DA - 2001 Jul 27 SP - 28291 EP - 28299 VL - 276 IS - 30 SN - 0021-9258, 0021-9258 KW - MutH protein KW - MutL protein KW - MutS protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - DNA repair KW - Mechanisms KW - J 02725:DNA KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17896477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Interaction+of+Escherichia+coli+MutS+and+MutL+at+a+DNA+Mismatch&rft.au=Schofield%2C+MJ%3BNayak%2C+S%3BScott%2C+TH%3BDu%2C+C%3BHsieh%2C+P&rft.aulast=Schofield&rft.aufirst=MJ&rft.date=2001-07-27&rft.volume=276&rft.issue=30&rft.spage=28291&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Mechanisms; DNA repair ER - TY - JOUR T1 - Mealybug b-proteobacterial endosymbionts contain g-proteobacterial symbionts AN - 864950243; 13694681 AB - Some insects have cultivated intimate relationships with mutualistic bacteria since their early evolutionary history. Most ancient 'primary' endosymbionts live within the cytoplasm of large, polyploid host cells of a specialized organ (bacteriome). Within their large, ovoid bacteriomes, mealybugs (Pseudococcidae) package the intracellular endosymbionts into 'mucus-filled' spheres, which surround the host cell nucleus and occupy most of the cytoplasm. The genesis of symbiotic spheres has not been determined, and they are structurally unlike eukaryotic cell vesicles. Recent molecular phylogenetic and fluorescent in situ hybridization (FISH) studies suggested that two unrelated bacterial species may share individual host cells, and that bacteria within spheres comprise these two species. Here we show that mealybug host cells do indeed harbour both b- and g-subdivision Proteobacteria, but they are not co-inhabitants of the spheres. Rather, we show that the symbiotic spheres themselves are b-proteobacterial cells. Thus, g-Proteobacteria live symbiotically inside b-Proteobacteria. This is the first report, to our knowledge, of an intracellular symbiosis involving two species of bacteria. JF - Nature AU - von Dohlen, Carol D AU - Kohler, Shawn AU - Alsop, Skylar T AU - McManus, William R AD - Present address: LDN, NICHD, National Institutes of Health, MSC 4480, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. Y1 - 2001/07/26/ PY - 2001 DA - 2001 Jul 26 SP - 433 EP - 436 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 412 IS - 6845 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts B: Bacteriology; Entomology Abstracts KW - Phylogeny KW - Symbiosis KW - Symbionts KW - Polyploidy KW - Endosymbionts KW - Pseudococcidae KW - Proteobacteria KW - Cytoplasm KW - Vesicles KW - Nuclei KW - Evolution KW - Fluorescence in situ hybridization KW - Z 05300:General KW - J 02430:Symbiosis, Antibiosis & Phages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864950243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Mealybug+b-proteobacterial+endosymbionts+contain+g-proteobacterial+symbionts&rft.au=von+Dohlen%2C+Carol+D%3BKohler%2C+Shawn%3BAlsop%2C+Skylar+T%3BMcManus%2C+William+R&rft.aulast=von+Dohlen&rft.aufirst=Carol&rft.date=2001-07-26&rft.volume=412&rft.issue=6845&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35086563 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Phylogeny; Polyploidy; Symbionts; Symbiosis; Endosymbionts; Cytoplasm; Vesicles; Nuclei; Evolution; Fluorescence in situ hybridization; Pseudococcidae; Proteobacteria DO - http://dx.doi.org/10.1038/35086563 ER - TY - JOUR T1 - Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. AN - 71005942; 11474661 AB - Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells. RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses. Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months (range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic-uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels. BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues. JF - The New England journal of medicine AU - Kreitman, R J AU - Wilson, W H AU - Bergeron, K AU - Raggio, M AU - Stetler-Stevenson, M AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA. kreitmar@mail.nih.gov Y1 - 2001/07/26/ PY - 2001 DA - 2001 Jul 26 SP - 241 EP - 247 VL - 345 IS - 4 SN - 0028-4793, 0028-4793 KW - Antibodies KW - 0 KW - Antineoplastic Agents KW - Enterotoxins KW - Exotoxins KW - Immunotoxins KW - RFB4(dsFv)-PE38 recombinant immunotoxin KW - Cladribine KW - 47M74X9YT5 KW - Abridged Index Medicus KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Cladribine -- therapeutic use KW - Aged KW - Drug Resistance KW - Pseudomonas KW - Recurrence KW - Hemolytic-Uremic Syndrome -- chemically induced KW - Adult KW - Remission Induction -- methods KW - Middle Aged KW - Female KW - Male KW - Exotoxins -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Immunotoxins -- adverse effects KW - Leukemia, Hairy Cell -- drug therapy KW - Exotoxins -- adverse effects KW - Immunotoxins -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71005942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Efficacy+of+the+anti-CD22+recombinant+immunotoxin+BL22+in+chemotherapy-resistant+hairy-cell+leukemia.&rft.au=Kreitman%2C+R+J%3BWilson%2C+W+H%3BBergeron%2C+K%3BRaggio%2C+M%3BStetler-Stevenson%2C+M%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2001-07-26&rft.volume=345&rft.issue=4&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Macrocyclization in the design of a conformationally constrained Grb2 SH2 domain inhibitor. AN - 71022999; 11459654 AB - Grubbs' olefin metathesis reaction was utilized to prepare a macrocyclic variant of a linear Grb2 SH2 domain antagonist in an attempt to induce a beta-bend conformation known to be required for high affinity binding. In extracellular Grb2 SH2 domain binding assays, the macrocyclic analogue exhibited an approximate 100-fold enhancement in binding potency relative to its linear counterpart. The macrocycle was not as effective in whole cell binding assays as would be expected based on its extracellular binding potency. JF - Bioorganic & medicinal chemistry letters AU - Gao, Y AU - Voigt, J AU - Wu, J X AU - Yang, D AU - Burke, T R AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI at Frederick, National Institutes of Health, MD 21702, Frederick, USA. Y1 - 2001/07/23/ PY - 2001 DA - 2001 Jul 23 SP - 1889 EP - 1892 VL - 11 IS - 14 SN - 0960-894X, 0960-894X KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Peptides KW - Proteins KW - Receptors, Drug KW - Tyrosine KW - 42HK56048U KW - Index Medicus KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Models, Molecular KW - Humans KW - Cell Division -- drug effects KW - Cyclization KW - Drug Design KW - Structure-Activity Relationship KW - Protein Binding -- physiology KW - Signal Transduction -- physiology KW - Breast Neoplasms -- pathology KW - Enzyme-Linked Immunosorbent Assay KW - Inhibitory Concentration 50 KW - Molecular Conformation KW - Receptors, Drug -- metabolism KW - src Homology Domains -- physiology KW - Proteins -- antagonists & inhibitors KW - Tyrosine -- pharmacology KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Receptors, Drug -- chemistry KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Proteins -- metabolism KW - src Homology Domains -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71022999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Macrocyclization+in+the+design+of+a+conformationally+constrained+Grb2+SH2+domain+inhibitor.&rft.au=Gao%2C+Y%3BVoigt%2C+J%3BWu%2C+J+X%3BYang%2C+D%3BBurke%2C+T+R&rft.aulast=Gao&rft.aufirst=Y&rft.date=2001-07-23&rft.volume=11&rft.issue=14&rft.spage=1889&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Linkage of Eco RI Dissociation from its Specific DNA Recognition Site to Water Activity, Salt Concentration, and pH: Separating their Roles in Specific and Non-specific Binding AN - 17921992; 5145486 AB - We have measured the dependencies of both the dissociation rate of specifically bound EcoRI endonuclease and the ratio of non-specific and specific association constants on water activity, salt concentration, and pH in order to distinguish the contributions of these solution components to specific and non-specific binding. For proteins such as EcoRI that locate their specific recognition site efficiently by diffusing along non-specific DNA, the specific site dissociation rate can be separated into two steps: an equilibrium between non-specific and specific binding of the enzyme to DNA, and the dissociation of non-specifically bound protein. We demonstrated previously that the osmotic dependence of the dissociation rate is dominated by the equilibrium between specific and non-specific binding that is independent of the osmolyte nature. The remaining osmotic sensitivity linked to the dissociation of non-specifically bound protein depends significantly on the particular osmolyte used, indicating a change in solute-accessible surface area. In contrast, the dissociation of non-specifically bound enzyme accounts for almost all the pH and salt-dependencies. We observed virtually no pH-dependence of the equilibrium between specific and non-specific binding measured by the competition assay. The observed weak salt-sensitivity of the ratio of specific and non-specific association constants is consistent with an osmotic, rather than electrostatic, action. The seeming lack of a dependence on viscosity suggests the rate-limiting step in dissociation of non-specifically bound protein is a discrete conformational change rather than a general diffusion of the protein away from the DNA. JF - Journal of Molecular Biology AU - Sidorova, N Y AU - Rau, D C AD - Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA Y1 - 2001/07/20/ PY - 2001 DA - 2001 Jul 20 SP - 801 EP - 816 PB - Academic Press VL - 310 IS - 4 SN - 0022-2836, 0022-2836 KW - conformation KW - dissociation KW - deoxyribonuclease EcoRI KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Salts KW - Escherichia coli KW - pH effects KW - Water KW - J 02725:DNA KW - N 14712:DNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17921992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Linkage+of+Eco+RI+Dissociation+from+its+Specific+DNA+Recognition+Site+to+Water+Activity%2C+Salt+Concentration%2C+and+pH%3A+Separating+their+Roles+in+Specific+and+Non-specific+Binding&rft.au=Sidorova%2C+N+Y%3BRau%2C+D+C&rft.aulast=Sidorova&rft.aufirst=N&rft.date=2001-07-20&rft.volume=310&rft.issue=4&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2001.4781 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Salts; pH effects; Water DO - http://dx.doi.org/10.1006/jmbi.2001.4781 ER - TY - JOUR T1 - Crystal Structure of the Dimeric C-terminal Domain of TonB Reveals a Novel Fold AN - 17893162; 5142079 AB - The TonB-dependent complex of Gram-negative bacteria couples the inner membrane proton motive force to the active transport of iron super(.)siderophore and vitamin B sub(12) across the outer membrane. The structural basis of that process has not been described so far in full detail. The crystal structure of the C-terminal domain of TonB from Escherichia coli has now been solved by multiwavelength anomalous diffraction and refined at 1.55-Aa resolution, providing the first evidence that this region of TonB (residues 164-239) dimerizes. Moreover, the structure shows a novel architecture that has no structural homologs among any known proteins. The dimer of the C-terminal domain of TonB is cylinder-shaped with a length of 65 Aa and a diameter of 25 Aa. Each monomer contains three beta strands and a single alpha helix. The two monomers are intertwined with each other, and all six beta -strands of the dimer make a large antiparallel beta -sheet. We propose a plausible model of binding of TonB to FhuA and FepA, two TonB-dependent outer-membrane receptors. JF - Journal of Biological Chemistry AU - Chang, C AU - Mooser, A AU - Plueckthun, A AU - Wlodawer, A AD - Macromolecular Crystallography Laboratory, NCI, National Institutes of Health, Frederick, Maryland 21702, USA, plueckthun@biocfebs.unizh.ch Y1 - 2001/07/20/ PY - 2001 DA - 2001 Jul 20 SP - 27535 EP - 27540 VL - 276 IS - 29 SN - 0021-9258, 0021-9258 KW - TonB protein KW - Microbiology Abstracts B: Bacteriology KW - Dimers KW - Protein folding KW - Secondary structure KW - Outer membranes KW - Crystal structure KW - Escherichia coli KW - X-ray diffraction KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17893162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Crystal+Structure+of+the+Dimeric+C-terminal+Domain+of+TonB+Reveals+a+Novel+Fold&rft.au=Chang%2C+C%3BMooser%2C+A%3BPlueckthun%2C+A%3BWlodawer%2C+A&rft.aulast=Chang&rft.aufirst=C&rft.date=2001-07-20&rft.volume=276&rft.issue=29&rft.spage=27535&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Protein folding; Crystal structure; X-ray diffraction; Dimers; Outer membranes; Secondary structure ER - TY - JOUR T1 - Somatic mosaicism in Wiskott--Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism. AN - 71034200; 11447283 AB - Somatic mosaicism caused by in vivo reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. In most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott--Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wada, T AU - Schurman, S H AU - Otsu, M AU - Garabedian, E K AU - Ochs, H D AU - Nelson, D L AU - Candotti, F AD - Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/07/17/ PY - 2001 DA - 2001 Jul 17 SP - 8697 EP - 8702 VL - 98 IS - 15 SN - 0027-8424, 0027-8424 KW - Antigens, CD3 KW - 0 KW - Complementarity Determining Regions KW - Proteins KW - Receptors, Antigen, T-Cell, alpha-beta KW - WAS protein, human KW - Wiskott-Aldrich Syndrome Protein KW - Index Medicus KW - Pedigree KW - Protein Biosynthesis KW - T-Lymphocytes -- metabolism KW - T-Lymphocytes -- cytology KW - Antigens, CD3 -- biosynthesis KW - Humans KW - Complementarity Determining Regions -- genetics KW - Adult KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics KW - Mutagenesis, Insertional KW - Male KW - Female KW - Mosaicism KW - Wiskott-Aldrich Syndrome -- genetics KW - Proteins -- genetics KW - Wiskott-Aldrich Syndrome -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71034200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Somatic+mosaicism+in+Wiskott--Aldrich+syndrome+suggests+in+vivo+reversion+by+a+DNA+slippage+mechanism.&rft.au=Wada%2C+T%3BSchurman%2C+S+H%3BOtsu%2C+M%3BGarabedian%2C+E+K%3BOchs%2C+H+D%3BNelson%2C+D+L%3BCandotti%2C+F&rft.aulast=Wada&rft.aufirst=T&rft.date=2001-07-17&rft.volume=98&rft.issue=15&rft.spage=8697&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 1996 Jul;13(3):290-5 [8673127] J Clin Invest. 1996 Jun 1;97(11):2627-34 [8647957] Cell. 1997 Feb 21;88(4):543-51 [9038345] Pediatr Res. 1997 Apr;41(4 Pt 1):535-40 [9098856] Blood. 1997 Jul 1;90(1):70-5 [9207440] Eur J Hum Genet. 1997 May-Jun;5(3):137-48 [9272737] Springer Semin Immunopathol. 1998;19(4):435-58 [9618767] Blood. 1999 May 1;93(9):3008-16 [10216097] J Clin Invest. 1999 May 15;103(10):1371-7 [10330419] Annu Rev Immunol. 1999;17:905-29 [10358777] Nat Genet. 1999 Aug;22(4):379-83 [10431244] Gene Ther. 1999 Jun;6(6):1170-4 [10455421] J Exp Med. 1999 Nov 1;190(9):1329-42 [10544204] Blood. 1999 Dec 1;94(11):3872-82 [10572103] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):274-8 [10618408] Blood. 2000 Feb 15;95(4):1283-92 [10666201] J Immunol. 2000 Jul 15;165(2):1119-22 [10878391] Cell Mol Life Sci. 2000 Jun;57(6):914-31 [10950307] Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2532-7 [11226273] J Immunol. 2001 Apr 15;166(8):5245-9 [11290809] Cell. 1980 Oct;21(3):653-68 [6985477] Mol Biol Evol. 1987 May;4(3):203-21 [3328815] Blood. 1988 Nov;72(5):1735-9 [3263154] Genomics. 1989 Jan;4(1):60-7 [2563352] J Immunol. 1993 Oct 15;151(8):4383-90 [8409409] Immunodeficiency. 1993;4(1-4):271-6 [8167717] Cell. 1994 Aug 26;78(4):635-44 [8069912] J Clin Invest. 1994 Oct;94(4):1657-61 [7929843] J Pediatr. 1994 Dec;125(6 Pt 1):876-85 [7996359] Blood. 1995 May 1;85(9):2471-7 [7537115] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4706-10 [7753869] Blood. 1995 Nov 15;86(10):3797-804 [7579347] N Engl J Med. 1996 Nov 21;335(21):1563-7 [8900089] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. AN - 71020472; 11447287 AB - An emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. However, this topic has not been investigated on a genome scale with strains recovered from patients with well-defined clinical conditions. Staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. A DNA microarray representing >90% of the S. aureus genome was used to characterize genomic diversity, evolutionary relationships, and virulence gene distribution among 36 strains of divergent clonal lineages, including methicillin-resistant strains and organisms causing toxic shock syndrome. Genetic variation in S. aureus is very extensive, with approximately 22% of the genome comprised of dispensable genetic material. Eighteen large regions of difference were identified, and 10 of these regions have genes that encode putative virulence factors or proteins mediating antibiotic resistance. We find that lateral gene transfer has played a fundamental role in the evolution of S. aureus. The mec gene has been horizontally transferred into distinct S. aureus chromosomal backgrounds at least five times, demonstrating that methicillin-resistant strains have evolved multiple independent times, rather than from a single ancestral strain. This finding resolves a long-standing controversy in S. aureus research. The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a change in the host environment, rather than rapid geographic dissemination of a new hypervirulent strain. DNA microarray analysis of large samples of clinically characterized strains provides broad insights into evolution, pathogenesis, and disease emergence. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Fitzgerald, J R AU - Sturdevant, D E AU - Mackie, S M AU - Gill, S R AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Y1 - 2001/07/17/ PY - 2001 DA - 2001 Jul 17 SP - 8821 EP - 8826 VL - 98 IS - 15 SN - 0027-8424, 0027-8424 KW - Index Medicus KW - Staphylococcal Infections -- epidemiology KW - Genetic Variation KW - Animals KW - Cattle KW - Electrophoresis KW - Blotting, Southern -- methods KW - Staphylococcal Infections -- veterinary KW - Sheep KW - Humans KW - Polymerase Chain Reaction -- methods KW - Chromosomes, Bacterial KW - Staphylococcal Infections -- microbiology KW - Shock, Septic -- veterinary KW - Methicillin Resistance -- genetics KW - Shock, Septic -- microbiology KW - Genome, Bacterial KW - Staphylococcus aureus -- genetics KW - Staphylococcus aureus -- pathogenicity KW - Disease Outbreaks KW - Shock, Septic -- epidemiology KW - Staphylococcus aureus -- classification KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71020472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Evolutionary+genomics+of+Staphylococcus+aureus%3A+insights+into+the+origin+of+methicillin-resistant+strains+and+the+toxic+shock+syndrome+epidemic.&rft.au=Fitzgerald%2C+J+R%3BSturdevant%2C+D+E%3BMackie%2C+S+M%3BGill%2C+S+R%3BMusser%2C+J+M&rft.aulast=Fitzgerald&rft.aufirst=J&rft.date=2001-07-17&rft.volume=98&rft.issue=15&rft.spage=8821&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Microbiol. 2000 Mar;38(3):1008-15 [10698988] Science. 1999 May 28;284(5419):1520-3 [10348738] J Bacteriol. 2001 Jan;183(1):63-70 [11114901] EMBO J. 2000 Dec 15;19(24):6637-43 [11118198] Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14668-73 [11121067] J Immunol. 2001 Jan 1;166(1):669-77 [11123352] Infect Immun. 1979 Sep;25(3):902-11 [259057] Proc Natl Acad Sci U S A. 1990 Jan;87(1):225-9 [1967495] J Clin Microbiol. 1992 Aug;30(8):2058-63 [1500513] Science. 1993 Jan 8;259(5092):227-30 [8093647] J Clin Microbiol. 1995 Feb;33(2):376-80 [7714195] J Bacteriol. 1996 Mar;178(5):1274-82 [8631702] Microbiology. 1997 Jul;143 ( Pt 7):2395-405 [9245821] Epidemiol Infect. 1997 Oct;119(2):261-9 [9363026] Antimicrob Agents Chemother. 1999 Jun;43(6):1449-58 [10348769] Infect Immun. 2000 Aug;68(8):4407-15 [10899837] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations of p14ARF, p53, and p73 genes involved in the E2F-1-mediated apoptotic pathways in non-small cell lung carcinoma. AN - 71024529; 11454718 AB - Overexpression of E2F-1 induces apoptosis by both a p14ARF-p53- and a p73-mediated pathway. p14ARF is the alternate tumor suppressor product of the INK4a/ARF locus that is inactivated frequently in lung carcinogenesis. Because p14ARF stabilizes p53, it has been proposed that the loss of p14ARF is functionally equivalent to a p53 mutation. We have tested this hypothesis by examining the genomic status of the unique exon 1beta of p14ARF in 53 human cell lines and 86 primary non-small cell lung carcinomas and correlated this with previously characterized alterations of p53. Homozygous deletions of p14ARF were detected in 12 of 53 (23%) cell lines and 16 of 86 (19%) primary tumors. A single cell line, but no primary tumors, harbored an intragenic mutation. The deletion of p14ARF was inversely correlated with the loss of p53 in the majority of cell lines (P = 0.02), but this relationship was not maintained among primary tumors (P = 0.5). E2F-1 can also induce p73 via a p53-independent apoptotic pathway. Although we did not observe inactivation of p73 by either mutation or DNA methylation, haploinsufficiency of p73 correlated positively with either p14ARF or p53 mutation or both (P = 0.01) in primary non-small cell lung carcinomas. These data are consistent with the current model of p14ARF and p53 interaction as a complex network rather than a simple linear pathway and indicate a possible role for an E2F-1-mediated failsafe, p53-independent, apoptotic pathway involving p73 in human lung carcinogenesis. JF - Cancer research AU - Nicholson, S A AU - Okby, N T AU - Khan, M A AU - Welsh, J A AU - McMenamin, M G AU - Travis, W D AU - Jett, J R AU - Tazelaar, H D AU - Trastek, V AU - Pairolero, P C AU - Corn, P G AU - Herman, J G AU - Liotta, L A AU - Caporaso, N E AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2001/07/15/ PY - 2001 DA - 2001 Jul 15 SP - 5636 EP - 5643 VL - 61 IS - 14 SN - 0008-5472, 0008-5472 KW - Carrier Proteins KW - 0 KW - Cell Cycle Proteins KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - E2F1 Transcription Factor KW - E2F1 protein, human KW - Nuclear Proteins KW - Proteins KW - Retinoblastoma-Binding Protein 1 KW - Transcription Factors KW - Tumor Protein p73 KW - Tumor Suppressor Protein p14ARF KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - p73 protein, human KW - Index Medicus KW - Nuclear Proteins -- genetics KW - Genes, Tumor Suppressor KW - DNA Mutational Analysis KW - Humans KW - DNA-Binding Proteins -- genetics KW - Gene Deletion KW - DNA, Neoplasm -- chemistry KW - Base Sequence KW - Loss of Heterozygosity KW - Tumor Cells, Cultured KW - DNA, Neoplasm -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Mutation KW - Signal Transduction KW - Male KW - Female KW - Transcription Factors -- physiology KW - Apoptosis KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Lung Neoplasms -- genetics KW - Proteins -- genetics KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71024529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Alterations+of+p14ARF%2C+p53%2C+and+p73+genes+involved+in+the+E2F-1-mediated+apoptotic+pathways+in+non-small+cell+lung+carcinoma.&rft.au=Nicholson%2C+S+A%3BOkby%2C+N+T%3BKhan%2C+M+A%3BWelsh%2C+J+A%3BMcMenamin%2C+M+G%3BTravis%2C+W+D%3BJett%2C+J+R%3BTazelaar%2C+H+D%3BTrastek%2C+V%3BPairolero%2C+P+C%3BCorn%2C+P+G%3BHerman%2C+J+G%3BLiotta%2C+L+A%3BCaporaso%2C+N+E%3BHarris%2C+C+C&rft.aulast=Nicholson&rft.aufirst=S&rft.date=2001-07-15&rft.volume=61&rft.issue=14&rft.spage=5636&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse. AN - 70984327; 11435319 AB - Erythropoietin and its receptor are required for definitive erythropoiesis and maturation of erythroid progenitor cells. Mice lacking the erythropoietin receptor exhibit severe anemia and die at about embryonic day 13.5. This phenotype can be rescued by the human erythropoietin receptor transgene. Animals expressing only the human erythropoietin receptor survived through adulthood with normal hematologic parameters and appeared to respond appropriately to induced anemic stress. In addition to restoration of erythropoiesis during development, the cardiac defect associated with embryos lacking the erythropoietin receptor was corrected and the increased apoptosis in fetal liver, heart, and brain in the erythropoietin receptor null phenotype was markedly reduced. These studies indicate that no species barrier exists between mouse and human erythropoietin receptor and that the human erythropoietin receptor transgene is able to provide specific expression in hematopoietic and other selected tissues to rescue erythropoiesis and other organ defects observed in the erythropoietin receptor null mouse. JF - Blood AU - Yu, X AU - Lin, C S AU - Costantini, F AU - Noguchi, C T AD - Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD 20892-1822, USA. Y1 - 2001/07/15/ PY - 2001 DA - 2001 Jul 15 SP - 475 EP - 477 VL - 98 IS - 2 SN - 0006-4971, 0006-4971 KW - RNA, Messenger KW - 0 KW - Receptors, Erythropoietin KW - Erythropoietin KW - 11096-26-7 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Apoptosis KW - Spleen -- metabolism KW - Hematopoietic Stem Cells -- chemistry KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Anemia -- chemically induced KW - RNA, Messenger -- analysis KW - Gene Expression KW - Bone Marrow -- metabolism KW - Mice KW - Mice, Transgenic KW - Hematopoietic Stem Cells -- metabolism KW - Erythropoietin -- physiology KW - Mice, Knockout KW - In Situ Nick-End Labeling KW - Anemia -- genetics KW - Crosses, Genetic KW - Bone Marrow Cells -- cytology KW - Colony-Forming Units Assay KW - Male KW - Female KW - Anemia -- therapy KW - Receptors, Erythropoietin -- genetics KW - Erythropoiesis -- genetics KW - Receptors, Erythropoietin -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70984327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=The+human+erythropoietin+receptor+gene+rescues+erythropoiesis+and+developmental+defects+in+the+erythropoietin+receptor+null+mouse.&rft.au=Yu%2C+X%3BLin%2C+C+S%3BCostantini%2C+F%3BNoguchi%2C+C+T&rft.aulast=Yu&rft.aufirst=X&rft.date=2001-07-15&rft.volume=98&rft.issue=2&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 2002 May 15;99(10):3873-4; author reply 3874-5 [12014371] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lyn is required for normal stem cell factor-induced proliferation and chemotaxis of primary hematopoietic cells. AN - 70977692; 11435302 AB - Stem cell factor (SCF) binds to c-Kit and is an important mediator of survival, growth, and function of hematopoietic progenitor cells and mast cells. Lyn and other Src family members are activated by SCF and associate with phosphorylated tyrosine residues in the c-Kit juxtamembrane region. However, studies using c-Kit mutants incapable of directly recruiting Src family members suggest this kinase family plays a minimal role in c-Kit stimulus-response coupling mechanisms. The objective of this study was to specifically target Lyn and subsequently address its role in SCF-mediated responses of primary hematopoietic progenitor cells and mast cells. To this end, a dominant-inhibitory Lyn mutant and Lyn-deficient mice were used. Transfection of normal murine mast cells with kinase-inactive Lyn impaired SCF-induced growth. Further, SCF-induced proliferation and chemotaxis of Lyn-deficient mast cells were less than for wild-type mast cells. SCF-induced growth of progenitor cells lacking Lyn was also reduced compared with that of wild-type progenitor cells. Impairment of SCF-mediated responses of Lyn-deficient mast cells and progenitor cells did not result from reductions in surface expression of c-Kit. These studies demonstrate that Lyn is required for normal SCF-mediated responses of primary progenitors and for a differentiated lineage. JF - Blood AU - O'Laughlin-Bunner, B AU - Radosevic, N AU - Taylor, M L AU - Shivakrupa AU - DeBerry, C AU - Metcalfe, D D AU - Zhou, M AU - Lowell, C AU - Linnekin, D AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute-Frederick, MD 21702, USA. Y1 - 2001/07/15/ PY - 2001 DA - 2001 Jul 15 SP - 343 EP - 350 VL - 98 IS - 2 SN - 0006-4971, 0006-4971 KW - Stem Cell Factor KW - 0 KW - lyn protein-tyrosine kinase KW - EC 2.7.10.2 KW - src-Family Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Gene Expression KW - Mice KW - Mast Cells -- cytology KW - Mice, Knockout KW - Bone Marrow Cells -- metabolism KW - Transfection KW - Cells, Cultured KW - Mast Cells -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Bone Marrow Cells -- cytology KW - Mutation KW - src-Family Kinases -- genetics KW - src-Family Kinases -- deficiency KW - Stem Cell Factor -- pharmacology KW - Hematopoietic Stem Cells -- cytology KW - Cell Division -- drug effects KW - Chemotaxis -- drug effects KW - src-Family Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70977692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Lyn+is+required+for+normal+stem+cell+factor-induced+proliferation+and+chemotaxis+of+primary+hematopoietic+cells.&rft.au=O%27Laughlin-Bunner%2C+B%3BRadosevic%2C+N%3BTaylor%2C+M+L%3BShivakrupa%3BDeBerry%2C+C%3BMetcalfe%2C+D+D%3BZhou%2C+M%3BLowell%2C+C%3BLinnekin%2C+D&rft.aulast=O%27Laughlin-Bunner&rft.aufirst=B&rft.date=2001-07-15&rft.volume=98&rft.issue=2&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiretroviral therapy effects on genetic and morphologic end points in lymphocytes and sperm of men with human immunodeficiency virus infection. AN - 70948137; 11424008 AB - Many human immunodeficiency virus (HIV)-infected persons receive prolonged treatment with DNA-reactive antiretroviral drugs. A prospective study was conducted of 26 HIV-infected men who provided samples before treatment and at multiple times after beginning treatment, to investigate effects of antiretrovirals on lymphocyte and sperm chromosomes and semen quality. Several antiretroviral regimens, all including a nucleoside component, were used. Lymphocyte metaphase analysis and sperm fluorescence in situ hybridization were used for cytogenetic studies. Semen analyses included conventional parameters (volume, concentration, viability, motility, and morphology). No significant effects on cytogenetic parameters, semen volume, or sperm concentration were detected. However, there were significant improvements in sperm motility for men with study entry CD4 cell counts >200 cells/mm(3), sperm morphology for men with entry CD4 cell counts < or =200 cells/mm(3), and the percentage of viable sperm in both groups. These findings suggest that nucleoside-containing antiretrovirals administered via recommended protocols do not induce chromosomal changes in lymphocytes or sperm but may produce improvements in semen quality. JF - The Journal of infectious diseases AU - Robbins, W A AU - Witt, K L AU - Haseman, J K AU - Dunson, D B AU - Troiani, L AU - Cohen, M S AU - Hamilton, C D AU - Perreault, S D AU - Libbus, B AU - Beyler, S A AU - Raburn, D J AU - Tedder, S T AU - Shelby, M D AU - Bishop, J B AD - National Institute of Environmental Health Sciences, Laboratory of Toxicology, Research Triangle Park, North Carolina, USA. wrobbins@sonnet.ucla.edu Y1 - 2001/07/15/ PY - 2001 DA - 2001 Jul 15 SP - 127 EP - 135 VL - 184 IS - 2 SN - 0022-1899, 0022-1899 KW - Anti-HIV Agents KW - 0 KW - Reverse Transcriptase Inhibitors KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Aneuploidy KW - Humans KW - Adult KW - In Situ Hybridization, Fluorescence KW - Middle Aged KW - Longitudinal Studies KW - CD4 Lymphocyte Count KW - Male KW - Diploidy KW - Anti-HIV Agents -- adverse effects KW - Lymphocytes -- metabolism KW - Chromosomes -- drug effects KW - Chromosome Breakage KW - Lymphocytes -- pathology KW - Reverse Transcriptase Inhibitors -- adverse effects KW - Anti-HIV Agents -- therapeutic use KW - Metaphase -- drug effects KW - Spermatozoa -- drug effects KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70948137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Antiretroviral+therapy+effects+on+genetic+and+morphologic+end+points+in+lymphocytes+and+sperm+of+men+with+human+immunodeficiency+virus+infection.&rft.au=Robbins%2C+W+A%3BWitt%2C+K+L%3BHaseman%2C+J+K%3BDunson%2C+D+B%3BTroiani%2C+L%3BCohen%2C+M+S%3BHamilton%2C+C+D%3BPerreault%2C+S+D%3BLibbus%2C+B%3BBeyler%2C+S+A%3BRaburn%2C+D+J%3BTedder%2C+S+T%3BShelby%2C+M+D%3BBishop%2C+J+B&rft.aulast=Robbins&rft.aufirst=W&rft.date=2001-07-15&rft.volume=184&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathogenicity and Convalescent Excretion of Campylobacter in Rural Egyptian Children AN - 18591336; 5461409 AB - Campylobacter infection in developing countries has not received much public health attention because of the observation that infections are not associated with disease beyond the first 6 months of life. A cohort of 397 Egyptian children aged less than 3 years, who were observed twice weekly during 1995-1998, experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child-year. A total of 13% of the Campylobacter diarrheal episodes were characterized by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9 in infants aged less than 6 months, 1.5 in those 6-12 months, and 0.4 and 0.2 in the second and third years of life, respectively. Convalescent excretion of Campylobacter after a diarrheal episode might be enhancing transmission and contributing to this high incidence. Observed risk factors for Campylobacter diarrhea were poor hygienic conditions and the presence of animals in the house. Regardless of the child's age, a first infection by Campylobacter was associated with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however, subsequent infections were associated with diarrhea only in children aged less than 6 months. This observation that natural infection did not confer protection during the first 6 months of life poses a challenge to vaccine development. JF - American Journal of Epidemiology AU - Rao, M R AU - Naficy, AB AU - Savarino, S J AU - Abu-Elyazeed, R AU - Wierzba, T F AU - Peruski, L F AU - Abdel-Messih, I AU - Frenck, R AU - Clemens, J D AD - Epidemiology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2001/07/15/ PY - 2001 DA - 2001 Jul 15 SP - 166 EP - 173 VL - 154 IS - 2 SN - 0002-9262, 0002-9262 KW - Microbiology Abstracts B: Bacteriology KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18591336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Pathogenicity+and+Convalescent+Excretion+of+Campylobacter+in+Rural+Egyptian+Children&rft.au=Rao%2C+M+R%3BNaficy%2C+AB%3BSavarino%2C+S+J%3BAbu-Elyazeed%2C+R%3BWierzba%2C+T+F%3BPeruski%2C+L+F%3BAbdel-Messih%2C+I%3BFrenck%2C+R%3BClemens%2C+J+D&rft.aulast=Rao&rft.aufirst=M&rft.date=2001-07-15&rft.volume=154&rft.issue=2&rft.spage=166&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Parental Occupational Exposures to Chemicals and Incidence of Neuroblastoma in Offspring AN - 18488130; 5461406 AB - To evaluate the effects of parental occupational chemical exposures on incidence of neuroblastoma in offspring, the authors conducted a multicenter case-control study, using detailed exposure information that allowed examination of specific chemicals. Cases were 538 children aged 19 years who were newly diagnosed with confirmed neuroblastoma in 1992-1994 and were registered at any of 139 participating hospitals in the United States and Canada. One age-matched control for each of 504 cases was selected through random digit dialing. Self-reported exposures were reviewed by an industrial hygienist, and improbable exposures were reclassified. Effect estimates were calculated using unconditional logistic regression, adjusting for child's age and maternal demographic factors. Maternal exposures to most chemicals were not associated with neuroblastoma. Paternal exposures to hydrocarbons such as diesel fuel (odds ratio (OR) = 1.5; 95% confidence interval (CI): 0.8, 2.6), lacquer thinner (OR = 3.5; 95% CI: 1.6, 7.8), and turpentine (OR = 10.4; 95% CI: 2.4, 44.8) were associated with an increased incidence of neuroblastoma, as were exposures to wood dust (OR = 1.5; 95% CI: 0.8, 2.8) and solders (OR = 2.6; 95% CI: 0.9, 7.1). The detailed exposure information available in this study has provided additional clues about the role of parental occupation as a risk factor for neuroblastoma. JF - American Journal of Epidemiology AU - De Roos, AJ AU - Olshan, A F AU - Teschke, K AU - Poole, C AU - Savitz, DA AU - Blatt, J AU - Bondy, M L AU - Pollock, B H AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA Y1 - 2001/07/15/ PY - 2001 DA - 2001 Jul 15 SP - 106 EP - 114 VL - 154 IS - 2 SN - 0002-9262, 0002-9262 KW - neuroblastoma KW - offspring KW - turpentine KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - X 24151:Acute exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18488130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Parental+Occupational+Exposures+to+Chemicals+and+Incidence+of+Neuroblastoma+in+Offspring&rft.au=De+Roos%2C+AJ%3BOlshan%2C+A+F%3BTeschke%2C+K%3BPoole%2C+C%3BSavitz%2C+DA%3BBlatt%2C+J%3BBondy%2C+M+L%3BPollock%2C+B+H&rft.aulast=De+Roos&rft.aufirst=AJ&rft.date=2001-07-15&rft.volume=154&rft.issue=2&rft.spage=106&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth. AN - 71016976; 11463412 AB - DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) is highly effective against most malaria-transmitting mosquitoes and is being widely used in malaria-endemic areas. The metabolite, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has been linked to preterm birth in small studies, but these findings are inconclusive. Our aim was to investigate the association between DDE exposure and preterm birth. Our study was based on the US Collaborative Perinatal Project (CPP). From this study we selected a subset of more than 44000 eligible children born between 1959 and 1966 and measured the DDE concentration in their mothers' serum samples stored during pregnancy. Complete data were available for 2380 children, of whom 361 were born preterm and 221 were small-for-gestational age. The median maternal DDE concentration was 25 mg/L (range 3-178)-several fold higher than current US concentrations. The adjusted odds ratios (OR) of preterm birth increased steadily with increasing concentrations of serum DDE (ORs=1, 1.5, 1.6, 2.5, 3.1; trend p<0.0001). Adjusted odds of small-for-gestational-age also increased, but less consistently (ORs=1, 1.9, 1.7, 1.6, 2.6; trend p=0.04). After excluding preterm births, the association of DDE with small-for-gestational-age remained. The findings strongly suggest that DDT use increases preterm births, which is a major contributor to infant mortality. If this association is causal, it should be included in any assessment of the costs and benefits of vector control with DDT. JF - Lancet (London, England) AU - Longnecker, M P AU - Klebanoff, M A AU - Zhou, H AU - Brock, J W AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, PO Box 12233 MD A3-05, NC 27709, USA. longnecker@niehs.nih.gov Y1 - 2001/07/14/ PY - 2001 DA - 2001 Jul 14 SP - 110 EP - 114 VL - 358 IS - 9276 SN - 0140-6736, 0140-6736 KW - Insecticides KW - 0 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - DDT KW - CIW5S16655 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Gestational Age KW - Infant, Newborn KW - Infant Mortality KW - Pregnancy KW - Population Surveillance KW - Logistic Models KW - Risk Factors KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Obstetric Labor, Premature -- epidemiology KW - Insecticides -- adverse effects KW - DDT -- metabolism KW - Environmental Exposure -- analysis KW - Dichlorodiphenyl Dichloroethylene -- adverse effects KW - Environmental Exposure -- adverse effects KW - Obstetric Labor, Premature -- chemically induced KW - Infant, Small for Gestational Age KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71016976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Association+between+maternal+serum+concentration+of+the+DDT+metabolite+DDE+and+preterm+and+small-for-gestational-age+babies+at+birth.&rft.au=Longnecker%2C+M+P%3BKlebanoff%2C+M+A%3BZhou%2C+H%3BBrock%2C+J+W&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2001-07-14&rft.volume=358&rft.issue=9276&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 2001 Nov 17;358(9294):1732 [11728584] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroadaptation: Incubation of cocaine craving after withdrawal AN - 17923256; 5145077 AB - Relapse to cocaine addiction is frequently associated with subjective reports of craving, a poorly understood state that precedes and accompanies cocaine-seeking behaviours. It has been suggested that over the first few weeks of withdrawal from cocaine, human addicts become sensitized to drug-associated environmental cues that act as external stimuli for craving, although the evidence for this is inconsistent. Here we provide behavioural evidence from laboratory animals suggesting that the onset of craving is delayed and that craving does not decay, but rather increases progressively, over a two-month withdrawal period. We modelled cocaine-craving behaviour by using rats trained to press a lever to receive an intravenous injection of cocaine and then testing them under conditions in which lever-pressing could continue but the cocaine reward was no longer given. In this model, lever-pressing could continue but the cocaine reward was no longer given. In this model, lever-pressing drops to almost zero ("extinguishes") but can be temporarily reinstated by giving the animal an unearned "priming" injection of the drug, by administering some forms of stress, ore by presenting drug-associated cues - factors that the known to provoke drug craving in human addicts. JF - Nature AU - Grimm, J W AU - Hope, B T AU - Wise, R A AU - Shaham, Y AD - Behavioral Neuroscience Branch, Intramural Research Program, National Inst. on Drug Abuse, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, yshaham@intra.nida.nih.gov Y1 - 2001/07/12/ PY - 2001 DA - 2001 Jul 12 SP - 141 EP - 142 PB - Macmillan Publishers Ltd. VL - 412 IS - 6843 SN - 0028-0836, 0028-0836 KW - Neuroadaptation KW - drug craving KW - rats KW - Animal Behavior Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - Reinforcement KW - Cocaine KW - Drug addiction KW - Intravenous administration KW - Extinction KW - Withdrawal KW - Reinstatement KW - Drug dependence KW - Reviews KW - X 24180:Social poisons & drug abuse KW - Y 25817:Mammals (excluding primates) KW - N3 11139:Toxicological and psychoactive drug correlates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17923256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Neuroadaptation%3A+Incubation+of+cocaine+craving+after+withdrawal&rft.au=Grimm%2C+J+W%3BHope%2C+B+T%3BWise%2C+R+A%3BShaham%2C+Y&rft.aulast=Grimm&rft.aufirst=J&rft.date=2001-07-12&rft.volume=412&rft.issue=6843&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Drug addiction; Cocaine; Withdrawal; Extinction; Reinstatement; Drug dependence; Intravenous administration; Reinforcement ER - TY - JOUR T1 - Cell toxicity caused by products of the p(L) operon of bacteriophage lambda. AN - 71037299; 11470529 AB - Induction of a lambda prophage causes the death of the host cell even in the absence of phage replication and lytic functions due to expression of functions from the lambda p(L) operon. We genetically modified the lambda prophage to determine which lambda p(L) operon functions were involved in cell killing. Viability assays and flow cytometry were used to monitor cell death and filamentation. The kil gene was shown to cause cell death and filamentation as described previously. Another killing activity was mapped within the p(L) operon to the gam gene. Inspection of the DNA sequence showed that there are two possible translation start points for both kil and gam. In both cases, the shorter of the two possible products could cause cell killing. The shorter products were also sufficient for the known filamentation and recombination activities of the respective Kil and Gam functions. The expression level of the p(L) operon is down-regulated by Cro repressor. In the absence of Cro, higher p(L) expression levels allow either Kil or Gam to be lethal or growth inhibitory, whereas at lowered expression in Cro-repressed conditions, only Kil is lethal. The filamentation function of Kil and recombination activity of Gam are unaffected at Cro-repressed levels of expression. JF - Gene AU - Sergueev, K AU - Yu, D AU - Austin, S AU - Court, D AD - National Cancer Institute at Frederick, Gene Regulation and Chromosome Biology Laboratory, Frederick, MD 21702-1201, USA. Y1 - 2001/07/11/ PY - 2001 DA - 2001 Jul 11 SP - 227 EP - 235 VL - 272 IS - 1-2 SN - 0378-1119, 0378-1119 KW - Bacterial Proteins KW - 0 KW - Codon, Initiator KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Repressor Proteins KW - Transcription Factors KW - Viral Proteins KW - Viral Regulatory and Accessory Proteins KW - cIII protein, Bacteriophage lambda KW - gam protein, Coliphage KW - kil protein, E coli KW - phage repressor proteins KW - Index Medicus KW - Defective Viruses -- genetics KW - Bacterial Proteins -- genetics KW - Codon, Initiator -- genetics KW - Recombination, Genetic KW - Point Mutation KW - Gene Expression KW - Cell Division -- drug effects KW - Transcription Factors -- genetics KW - Repressor Proteins -- genetics KW - Gene Deletion KW - Viral Proteins -- genetics KW - Bacteriophage lambda -- genetics KW - Operon KW - Escherichia coli -- genetics KW - Escherichia coli -- virology KW - Escherichia coli -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71037299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Cell+toxicity+caused+by+products+of+the+p%28L%29+operon+of+bacteriophage+lambda.&rft.au=Sergueev%2C+K%3BYu%2C+D%3BAustin%2C+S%3BCourt%2C+D&rft.aulast=Sergueev&rft.aufirst=K&rft.date=2001-07-11&rft.volume=272&rft.issue=1-2&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bruton's tyrosine kinase is essential for hydrogen peroxide-induced calcium signaling. AN - 70970300; 11434777 AB - Using Btk-deficient DT40 cells and the transfectants expressing wild-type Btk or Btk mutants in either kinase (Arg(525) to Gln), Src homology 2 (SH2, Arg(307) to Ala), or pleckstrin homology (PH, Arg(28) to Cys) domains, we investigated the roles and structure-function relationships of Btk in hydrogen peroxide-induced calcium mobilization. Our genetic evidence showed that Btk deficiency resulted in a significant reduction in hydrogen peroxide-induced calcium response. This impaired calcium signaling is correlated with the complete elimination of IP3 production and the significantly reduced tyrosine phosphorylation of PLCgamma2 in Btk-deficient DT40 cells. All of these defects were fully restored by the expression of wild-type Btk in Btk-deficient DT40 cells. The data from the point mutation study revealed that a defect at any one of the three functional domains would prevent a full recovery of Btk-mediated hydrogen peroxide-induced intracellular calcium mobilization. However, mutation at either the SH2 or PH domain did not affect the hydrogen peroxide-induced activation of Btk. Mutation at the SH2 domain abrogates both IP3 generation and calcium release, while the mutant with the nonfunctional PH domain can partially activate PLCgamma2 and catalyze IP3 production but fails to produce significant calcium mobilization. Thus, these observations suggest that Btk-dependent tyrosine phosphorylation of PLCgamma2 is required but not sufficient for hydrogen peroxide-induced calcium mobilization. Furthermore, hydrogen peroxide stimulates a Syk-, but not Btk-, dependent tyrosine phosphorylation of B cell linker protein BLNK. The overall results, together with those reported earlier [Qin et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 7118], are consistent with the notion that functional SH2 and PH domains are required for Btk to form a complex with PLCgamma2 through BLNK in order to position the Btk, PLCgamma2, and phosphatidylinositol 4,5-bisphosphate in close proximity for efficient activation of PLCgamma2 and to maximize its catalytic efficiency for IP3 production. JF - Biochemistry AU - Qin, S AU - Chock, P B AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 50, Room 2134, Bethesda, Maryland 20892-8012, USA. Y1 - 2001/07/10/ PY - 2001 DA - 2001 Jul 10 SP - 8085 EP - 8091 VL - 40 IS - 27 SN - 0006-2960, 0006-2960 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - B cell linker protein KW - Blood Proteins KW - Carrier Proteins KW - Enzyme Precursors KW - Intracellular Signaling Peptides and Proteins KW - Isoenzymes KW - Phosphoproteins KW - platelet protein P47 KW - Tyrosine KW - 42HK56048U KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Agammaglobulinaemia tyrosine kinase KW - EC 2.7.10.1 KW - Protein-Tyrosine Kinases KW - SYK protein, human KW - EC 2.7.10.2 KW - Syk Kinase KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Enzyme Precursors -- metabolism KW - Humans KW - B-Lymphocytes -- metabolism KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism KW - Agammaglobulinemia -- genetics KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - B-Lymphocytes -- drug effects KW - src Homology Domains -- genetics KW - Phosphorylation KW - Enzyme Activation -- drug effects KW - Tyrosine -- metabolism KW - B-Lymphocytes -- enzymology KW - Phosphoproteins -- metabolism KW - Agammaglobulinemia -- enzymology KW - Type C Phospholipases -- antagonists & inhibitors KW - Phosphoproteins -- genetics KW - Carrier Proteins -- metabolism KW - Inositol 1,4,5-Trisphosphate -- biosynthesis KW - Intracellular Fluid -- metabolism KW - Blood Proteins -- genetics KW - Enzyme Activation -- genetics KW - Isoenzymes -- antagonists & inhibitors KW - Chickens KW - Transfection KW - Catalytic Domain -- genetics KW - Intracellular Fluid -- enzymology KW - Cell Line KW - Protein-Tyrosine Kinases -- genetics KW - Calcium Signaling -- drug effects KW - Hydrogen Peroxide -- pharmacology KW - Calcium Signaling -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - Protein-Tyrosine Kinases -- deficiency KW - Protein-Tyrosine Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70970300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Bruton%27s+tyrosine+kinase+is+essential+for+hydrogen+peroxide-induced+calcium+signaling.&rft.au=Qin%2C+S%3BChock%2C+P+B&rft.aulast=Qin&rft.aufirst=S&rft.date=2001-07-10&rft.volume=40&rft.issue=27&rft.spage=8085&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter. AN - 71023930; 11448988 AB - We have examined the relationship between transcription and chromatin structure using a tandem array of the mouse mammary tumor virus (MMTV) promoter driving a ras reporter. The array was visualized as a distinctive fluorescent structure in live cells stably transformed with a green fluorescent protein (GFP)-tagged glucocorticoid receptor (GR), which localizes to the repeated MMTV elements after steroid hormone treatment. Also found at the array by immunofluorescence were two different steroid receptor coactivators (SRC1 and CBP) with acetyltransferase activity, a chromatin remodeler (BRG1), and two transcription factors (NFI and AP-2). Within 3 h after hormone addition, arrays visualized by GFP-GR or DNA fluorescent in situ hybridization (FISH) decondensed to varying degrees, in the most pronounced cases from a approximately 0.5-microm spot to form a fiber 1-10 microm long. Arrays later recondensed by 3-8 h of hormone treatment. The degree of decondensation was proportional to the amount of transcript produced by the array as detected by RNA FISH. Decondensation was blocked by two different drugs that inhibit polymerase II, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) and alpha-amanitin. These observations demonstrate a role for polymerase in producing and maintaining decondensed chromatin. They also support fiber-packing models of higher order structure and suggest that transcription from a natural promoter may occur at much higher DNA-packing densities than reported previously. JF - The Journal of cell biology AU - Müller, W G AU - Walker, D AU - Hager, G L AU - McNally, J G AD - Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, 41 Library Dr., Bethesda, MD 20892, USA. Y1 - 2001/07/09/ PY - 2001 DA - 2001 Jul 09 SP - 33 EP - 48 VL - 154 IS - 1 SN - 0021-9525, 0021-9525 KW - Amanitins KW - 0 KW - Carrier Proteins KW - Chromatin KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Luminescent Proteins KW - NFI Transcription Factors KW - NFI-A2 protein, rat KW - Nuclear Proteins KW - Receptors, Glucocorticoid KW - Recombinant Fusion Proteins KW - Transcription Factor AP-2 KW - Transcription Factors KW - citrate-binding transport protein KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Dichlororibofuranosylbenzimidazole KW - 53-85-0 KW - DNA KW - 9007-49-2 KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - Ncoa1 protein, mouse KW - Nuclear Receptor Coactivator 1 KW - Smarca4 protein, mouse KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - In Situ Hybridization, Fluorescence KW - Receptors, Glucocorticoid -- metabolism KW - Mammary Tumor Virus, Mouse -- genetics KW - Microscopy, Fluorescence KW - Recombinant Fusion Proteins -- metabolism KW - Nuclear Proteins -- metabolism KW - Time Factors KW - DNA-Binding Proteins -- metabolism KW - Carrier Proteins -- metabolism KW - DNA -- metabolism KW - Dichlororibofuranosylbenzimidazole -- pharmacology KW - Luminescent Proteins -- metabolism KW - Mice KW - Genes, ras -- genetics KW - Transfection KW - Amanitins -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Promoter Regions, Genetic KW - Chromatin -- metabolism KW - Chromatin -- chemistry KW - Transcription, Genetic KW - Chromatin -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71023930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Large-scale+chromatin+decondensation+and+recondensation+regulated+by+transcription+from+a+natural+promoter.&rft.au=M%C3%BCller%2C+W+G%3BWalker%2C+D%3BHager%2C+G+L%3BMcNally%2C+J+G&rft.aulast=M%C3%BCller&rft.aufirst=W&rft.date=2001-07-09&rft.volume=154&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Cell Res. 1971 Dec;69(2):462-5 [4950441] J Biol Chem. 1994 Dec 16;269(50):31983-90 [7989375] Science. 1976 Sep 3;193(4256):848-56 [948749] J Mol Biol. 1978 Sep 5;124(1):223-41 [712832] Cell. 1979 Aug;17(4):835-48 [290410] Cell. 1980 Apr;19(4):973-80 [6155217] Eur J Cell Biol. 1981 Jun;24(2):298-308 [7285946] Eur J Cell Biol. 1982 Feb;26(2):325-32 [7067711] J Biol Chem. 1982 Jul 10;257(13):7730-6 [6282852] Chromosoma. 1982;87(1):33-48 [6186441] Science. 1983 Apr 29;220(4596):498-500 [6836293] Mol Cell Biol. 1983 Nov;3(11):2045-57 [6318079] J Cell Biol. 1984 Apr;98(4):1296-303 [6715406] EMBO J. 1987 May;6(5):1355-60 [3038519] J Biol Chem. 1995 Aug 11;270(32):19114-9 [7642577] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13634-7 [10570124] Methods. 1999 Nov;19(3):386-93 [10579933] J Mol Endocrinol. 1999 Dec;23(3):255-75 [10601972] Science. 2000 Feb 18;287(5456):1262-5 [10678832] Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59 [10839822] Nature. 2000 Sep 28;407(6803):471-5 [11028991] Nat Cell Biol. 2000 Dec;2(12):871-8 [11146650] Chromosoma. 1968;24(4):418-37 [5708273] Exp Cell Res. 1971 Jan;64(1):237-9 [5541974] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4845-50 [8643491] J Cell Biol. 1996 Dec;135(6 Pt 2):1685-700 [8991083] J Cell Biol. 1998 Mar 9;140(5):975-89 [9490713] Cell. 1998 May 1;93(3):321-4 [9590165] Nature. 1998 May 7;393(6680):88-91 [9590696] Annu Rev Biochem. 1998;67:545-79 [9759497] J Biol Chem. 1999 Mar 12;274(11):7072-81 [10066764] Chromosoma. 1999 Apr;108(1):1-9 [10199951] J Cell Biol. 1999 Jun 28;145(7):1341-54 [10385516] J Biol Chem. 1999 Oct 1;274(40):28590-7 [10497225] J Steroid Biochem Mol Biol. 1999 Jul-Aug;70(1-3):15-25 [10528999] Nature. 1961 Apr 22;190:372-3 [13764598] Proc Natl Acad Sci U S A. 1962 Apr 15;48:562-70 [13896377] Proc Natl Acad Sci U S A. 1963 Apr;49:544-51 [13957141] Science. 1963 May 31;140(3570):976-8 [13975649] Chromosoma. 1964 Apr 1;15:71-122 [14171171] EMBO J. 1987 Aug;6(8):2321-8 [2822386] Nucleic Acids Res. 1988 Jan 25;16(2):609-28 [2829133] Nature. 1988 Oct 6;335(6190):563-4 [3047590] J Biol Chem. 1989 Feb 5;264(4):2250-7 [2914905] Cell. 1989 Feb 24;56(4):631-9 [2917368] Cell. 1990 Apr 6;61(1):1-3 [2180581] Proc Natl Acad Sci U S A. 1990 May;87(10):3977-81 [2160080] Science. 1992 Mar 20;255(5051):1573-6 [1347958] Mol Cell Biol. 1992 May;12(5):2078-90 [1569941] EMBO J. 1992 Sep;11(9):3457-68 [1505524] Mol Cell Biol. 1992 Nov;12(11):4906-18 [1328867] Mol Endocrinol. 1994 May;8(5):568-76 [8058066] Cell. 1975 Jan;4(1):1-9 [1090375] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. AN - 70915909; 11406822 AB - Knowing the rate of addition of new granule cells to the adult dentate gyrus is critical to understanding the function of adult neurogenesis. Despite the large number of studies of neurogenesis in the adult dentate gyrus, basic questions about the magnitude of this phenomenon have never been addressed. The S-phase marker bromodeoxyuridine (BrdU) has been extensively used in recent studies of adult neurogenesis, but it has been carefully tested only in the embryonic brain. Here, we show that a high dose of BrdU (300 mg/kg) is a specific, quantitative, and nontoxic marker of dividing cells in the adult rat dentate gyrus, whereas lower doses label only a fraction of the S-phase cells. By using this high dose of BrdU along with a second S-phase marker, [(3)H]thymidine, we found that young adult rats have 9,400 dividing cells proliferating with a cell cycle time of 25 hours, which would generate 9,000 new cells each day, or more than 250,000 per month. Within 5-12 days of BrdU injection, a substantial pool of immature granule neurons, 50% of all BrdU-labeled cells in the dentate gyrus, could be identified with neuron-specific antibodies TuJ1 and TUC-4. This number of new granule neurons generated each month is 6% of the total size of the granule cell population and 30-60% of the size of the afferent and efferent populations (West et al. [1991] Anat Rec 231:482-497; Mulders et al. [1997] J Comp Neurol 385:83-94). The large number of the adult-generated granule cells supports the idea that these new neurons play an important role in hippocampal function. Copyright 2001 Wiley-Liss, Inc. JF - The Journal of comparative neurology AU - Cameron, H A AU - McKay, R D AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 USA. cameronh@ninds.nih.gov Y1 - 2001/07/09/ PY - 2001 DA - 2001 Jul 09 SP - 406 EP - 417 VL - 435 IS - 4 SN - 0021-9967, 0021-9967 KW - Antimetabolites KW - 0 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Rats KW - Animals KW - Cell Survival -- drug effects KW - Tissue Fixation KW - Male KW - Cell Cycle -- drug effects KW - Dentate Gyrus -- growth & development KW - Dentate Gyrus -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70915909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+comparative+neurology&rft.atitle=Adult+neurogenesis+produces+a+large+pool+of+new+granule+cells+in+the+dentate+gyrus.&rft.au=Cameron%2C+H+A%3BMcKay%2C+R+D&rft.aulast=Cameron&rft.aufirst=H&rft.date=2001-07-09&rft.volume=435&rft.issue=4&rft.spage=406&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+comparative+neurology&rft.issn=00219967&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The last exon of SNAP-23 regulates granule exocytosis from mast cells. AN - 70974734; 11350976 AB - SNAP-25 and its ubiquitous homolog SNAP-23 are members of the SNARE family of proteins that regulate membrane fusion during exocytosis. Although SNAP-23 has been shown to participate in a variety of intracellular transport processes, the structural domains of SNAP-23 that are required for its interaction with other SNAREs have not been determined. By employing deletion mutagenesis we found that deletion of the amino-terminal 18 amino acids of SNAP-23 (encoded in the first exon) dramatically inhibited binding of SNAP-23 to both the target SNARE syntaxin and the vesicle SNARE vesicle-associated membrane protein(VAMP). By contrast, deletion of the carboxyl-terminal 23 amino acids (encoded in the last exon) of SNAP-23 does not affect SNAP-23 binding to syntaxin but profoundly inhibits its binding to VAMP. To determine the functional relevance of the modular structure of SNAP-23, we overexpressed SNAP-23 in cells possessing the capacity to undergo regulated exocytosis. Expression of human SNAP-23 in a rat mast cell line significantly enhanced exocytosis, and this effect was not observed in transfectants expressing the carboxyl-terminal VAMP-binding mutant of SNAP-23. Despite considerable amino acid identity, we found that human SNAP-23 bound to SNAREs more efficiently than did rat SNAP-23. These data demonstrate that the introduction of a "better" SNARE binder into secretory cells augments exocytosis and defines the carboxyl terminus of SNAP-23 as an essential regulator of exocytosis in mast cells. JF - The Journal of biological chemistry AU - Vaidyanathan, V V AU - Puri, N AU - Roche, P A AD - Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/07/06/ PY - 2001 DA - 2001 Jul 06 SP - 25101 EP - 25106 VL - 276 IS - 27 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Membrane Proteins KW - Qa-SNARE Proteins KW - Qb-SNARE Proteins KW - Qc-SNARE Proteins KW - R-SNARE Proteins KW - SNAP23 protein, human KW - SNARE Proteins KW - Vesicular Transport Proteins KW - Index Medicus KW - Animals KW - Peptide Mapping KW - HeLa Cells KW - Humans KW - Membrane Proteins -- metabolism KW - Rabbits KW - Protein Binding KW - Binding Sites KW - Rats KW - Transfection KW - Exons KW - Carrier Proteins -- genetics KW - Exocytosis KW - Mast Cells -- physiology KW - Cytoplasmic Granules -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70974734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+last+exon+of+SNAP-23+regulates+granule+exocytosis+from+mast+cells.&rft.au=Vaidyanathan%2C+V+V%3BPuri%2C+N%3BRoche%2C+P+A&rft.aulast=Vaidyanathan&rft.aufirst=V&rft.date=2001-07-06&rft.volume=276&rft.issue=27&rft.spage=25101&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photoaffinity labeling of mouse fibroblast enzymes by a base excision repair intermediate. Evidence for the role of poly(ADP-ribose) polymerase-1 in DNA repair. AN - 70965495; 11340072 AB - To examine the interaction of mammalian base excision repair (BER) enzymes with DNA intermediates formed during BER, we used a novel photoaffinity labeling probe and mouse embryonic fibroblast cellular extracts. The probe was formed in situ, using an end-labeled oligonucleotide containing a synthetic abasic site; this site was incised by apurinic/apyrimidinic endonuclease creating a nick with 3'-hydroxyl and 5'-reduced sugar phosphate groups at the margins, and then a dNMP carrying a photoreactive adduct was added to the 3'-hydroxyl group. With near-UV light (312 nm) exposure of the extract/probe mixture, six proteins were strongly labeled. Four of these include poly(ADP-ribose) polymerase-1 (PARP-1) and the BER participants flap endonuclease-1, DNA polymerase beta, and apurinic/apyrimidinic endonuclease. The amount of the probe cross-linked to PARP-1 was greater than that cross-linked to the other proteins. The specificity of PARP-1 labeling was examined using various competitor oligonucleotides and DNA probes with alternate structures. PARP-1 labeling was stronger with a DNA representing a BER intermediate than with a nick in double-stranded DNA. These results indicate that proteins interacting preferentially with a photoreactive BER intermediate can be selected from the crude cellular extract. JF - The Journal of biological chemistry AU - Lavrik, O I AU - Prasad, R AU - Sobol, R W AU - Horton, J K AU - Ackerman, E J AU - Wilson, S H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/07/06/ PY - 2001 DA - 2001 Jul 06 SP - 25541 EP - 25548 VL - 276 IS - 27 SN - 0021-9258, 0021-9258 KW - Deoxycytosine Nucleotides KW - 0 KW - Isoenzymes KW - Photoaffinity Labels KW - 2'-deoxycytidine 5'-triphosphate KW - 2056-98-6 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Deoxycytosine Nucleotides -- metabolism KW - In Situ Nick-End Labeling KW - Animals KW - Base Sequence KW - Humans KW - Binding, Competitive KW - Spectrophotometry, Ultraviolet KW - Molecular Sequence Data KW - Mice KW - Nucleic Acid Conformation KW - Cell Line KW - Methyl Methanesulfonate -- pharmacology KW - Photoaffinity Labels -- metabolism KW - Fibroblasts -- enzymology KW - DNA Repair KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70965495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Photoaffinity+labeling+of+mouse+fibroblast+enzymes+by+a+base+excision+repair+intermediate.+Evidence+for+the+role+of+poly%28ADP-ribose%29+polymerase-1+in+DNA+repair.&rft.au=Lavrik%2C+O+I%3BPrasad%2C+R%3BSobol%2C+R+W%3BHorton%2C+J+K%3BAckerman%2C+E+J%3BWilson%2C+S+H&rft.aulast=Lavrik&rft.aufirst=O&rft.date=2001-07-06&rft.volume=276&rft.issue=27&rft.spage=25541&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impairment in motor learning of somatostatin null mutant mice. AN - 70964312; 11430867 AB - Somatostatin was first identified as a hypothalamic factor which inhibits the release of growth hormone from the anterior pituitary (somatotropin release inhibitory factor, SRIF). Both SRIF and its receptors were subsequently found widely distributed within and outside the nervous system, in the adult as well as in the developing organism. Reflecting this wide distribution, somatostatin has been implicated regulating a diverse array of biological processes. These include body growth, homeostasis, sensory perception, autonomous functions, rate of intestinal absorption, behavior, including cognition and memory, and developmental processes. We produced null mutant mice lacking somatostatin through targeted mutagenesis. The mutant mice are healthy, fertile, and superficially indistinguishable from their heterozygous and wildtype littermates. A 'first round' phenotype screen revealed that mice lacking somatostatin have elevated plasma growth hormone levels, despite normal body size, and have elevated basal plasma corticosterone levels. In order to uncover subtle and unexpected differences, we carried out a systematic behavioral phenotype screen which identified a significant impairment in motor learning revealed when increased demands were made on motor coordination. Motor coordination and motor learning require an intact cerebellum. While somatostatin is virtually absent from the adult cerebellum, the ligand and its receptor(s) are transiently expressed at high levels in the developing cerebellum. This result suggests the functional significance of transient expression of SRIF and its receptors in the development of the cerebellum. JF - Brain research AU - Zeyda, T AU - Diehl, N AU - Paylor, R AU - Brennan, M B AU - Hochgeschwender, U AD - Unit on Molecular Genetics, Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/07/06/ PY - 2001 DA - 2001 Jul 06 SP - 107 EP - 114 VL - 906 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Somatostatin KW - 51110-01-1 KW - Index Medicus KW - Animals KW - Movement Disorders -- metabolism KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Movement Disorders -- physiopathology KW - Hypothalamo-Hypophyseal System -- metabolism KW - Movement Disorders -- genetics KW - Mice KW - Psychomotor Performance -- physiology KW - Mice, Knockout KW - Somatostatin -- deficiency KW - Mice, Neurologic Mutants -- genetics KW - Somatostatin -- genetics KW - Neurons -- metabolism KW - Mice, Neurologic Mutants -- physiology KW - Learning -- physiology KW - Motor Activity -- physiology KW - Mice, Neurologic Mutants -- metabolism KW - Cerebellum -- physiopathology KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70964312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Impairment+in+motor+learning+of+somatostatin+null+mutant+mice.&rft.au=Zeyda%2C+T%3BDiehl%2C+N%3BPaylor%2C+R%3BBrennan%2C+M+B%3BHochgeschwender%2C+U&rft.aulast=Zeyda&rft.aufirst=T&rft.date=2001-07-06&rft.volume=906&rft.issue=1-2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cause-specific mortality associated with HIV and HTLV-II infections among injecting drug users in the USA. AN - 70962602; 11426075 AB - Human T-lymphotropic virus type II (HTLV-II) is widespread among injecting drug users (IDU) and may contribute to the risk of leukemia/lymphoma, neurodegenerative disease, and perhaps pneumonia, especially with HIV co-infection. In 1987--1991, 6570 IDU were tested for HIV and HTLV-II antibodies. In 1998, they were matched to the National Death Index. Numbers of observed deaths of each cause were compared by standardized mortality ratios with the numbers expected, using sex-, race-, age-, and year-specific rates in the general population. Relative risk (RR) associated with each virus, compared to uninfected drug users, was estimated by Poisson modeling. There were 1351 deaths, including 683 (15%) of 4604 participants who enrolled seronegative for both viruses; 328 (47%) of 701 who had HIV but not HTLV-II infection; 220 (21%) of 1033 who had HTLV-II but not HIV infection; and 120 (52%) of 232 who were infected by both viruses. Compared to the general population, mortality for participants with neither virus was increased 4.3-fold [95% confidence interval (CI), 4.0--4.7] and was significantly elevated for virtually every cause of death. With HIV, mortality from medical causes, but not external causes, was increased 3.7-fold (95% CI, 3.3--4.2), particularly with AIDS and related conditions. With HTLV-II, all-cause mortality was reduced (RR, 0.8; 95% CI, 0.7--0.9), with no statistically significant reduction or elevation for any specific cause. A non-significant excess of tuberculosis deaths (RR, 4.6; 95% CI, 0.8--25.2) was noted with HTLV-II, but there was no excess mortality from leukemia/lymphoma, other malignancies, or neurodegenerative disease. Without HIV or HTLV-II, IDU had profoundly increased mortality from medical and external causes. HIV was specifically associated with death due to AIDS and related conditions. HTLV-II infection was not significantly associated with mortality from any cause, suggesting that it is not a significant human pathogen, even when present with HIV infection. JF - AIDS (London, England) AU - Goedert, J J AU - Fung, M W AU - Felton, S AU - Battjes, R J AU - Engels, E A AD - Viral Epidemiology Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA. Y1 - 2001/07/06/ PY - 2001 DA - 2001 Jul 06 SP - 1295 EP - 1302 VL - 15 IS - 10 SN - 0269-9370, 0269-9370 KW - Index Medicus KW - AIDS/HIV KW - HIV Seroprevalence KW - Risk Factors KW - Humans KW - Cohort Studies KW - United States -- epidemiology KW - HIV Infections -- mortality KW - HTLV-II Infections -- mortality KW - HIV Infections -- epidemiology KW - Cause of Death KW - Substance Abuse, Intravenous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70962602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Cause-specific+mortality+associated+with+HIV+and+HTLV-II+infections+among+injecting+drug+users+in+the+USA.&rft.au=Goedert%2C+J+J%3BFung%2C+M+W%3BFelton%2C+S%3BBattjes%2C+R+J%3BEngels%2C+E+A&rft.aulast=Goedert&rft.aufirst=J&rft.date=2001-07-06&rft.volume=15&rft.issue=10&rft.spage=1295&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Finite element model of antibody penetration in a prevascular tumor nodule embedded in normal tissue AN - 17902163; 5175210 AB - We have developed a pharmacokinetic model for monoclonal antibodies (mAb) to aid in investigating protocols for targeting small primary tumors or sites of metastatic disease. The model describes the uptake of systemically-administered antibody by a prevascular spherical tumor nodule embedded in normal tissue. The model incorporates plasma kinetics, transcapillary transport, interstitial diffusion, binding reactions, and lymphatic clearance. Antigen internalization can easily be incorporated. Simulations obtained from a three-dimensional finite element analysis are used to assess errors in predictions from earlier models in which the influence of the normal tissue was collapsed into a boundary condition at the tumor surface. The model employing a Dirichlet boundary condition substantially overpredicted the mean total tumor mAb concentration at all times. Although the model with a concentration-dependent flux (composite) boundary condition underpredicted mAb concentration, the discrepancy with finite element results is only notable at early times. Sensitivity analyses were performed on mAb dose and on the coefficients for mAb diffusion in the tissue regions, since reported antibody diffusivity values have varied over 30-fold. The results of the study suggest that mAb diffusivity and mAb binding site density in tumors should have major influences on optimizing doses and scheduling of mAb administration in tumor targeting protocols. JF - Journal of Controlled Release AU - Banerjee, R K AU - Van Osdol, WW AU - Bungay, P M AU - Sung, C AU - Dedrick, R L AD - NIH/DBEPS, Building 13/3N17 MSC 5766, Bethesda, MD 20892-5766, USA, bungayp@mail.nih.gov Y1 - 2001/07/06/ PY - 2001 DA - 2001 Jul 06 SP - 193 EP - 202 VL - 74 IS - 1-3 SN - 0168-3659, 0168-3659 KW - penetration KW - pharmacokinetic KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Metastases KW - Monoclonal antibodies KW - Immunotherapy KW - Tumors KW - Controlled release KW - Vascular system KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17902163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Controlled+Release&rft.atitle=Finite+element+model+of+antibody+penetration+in+a+prevascular+tumor+nodule+embedded+in+normal+tissue&rft.au=Banerjee%2C+R+K%3BVan+Osdol%2C+WW%3BBungay%2C+P+M%3BSung%2C+C%3BDedrick%2C+R+L&rft.aulast=Banerjee&rft.aufirst=R&rft.date=2001-07-06&rft.volume=74&rft.issue=1-3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Journal+of+Controlled+Release&rft.issn=01683659&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumors; Vascular system; Monoclonal antibodies; Metastases; Immunotherapy; Controlled release ER - TY - JOUR T1 - Effect of Retroviral Endostatin Gene Transfer on Subcutaneous and Intraperitoneal Growth of Murine Tumors AN - 18175247; 5176660 AB - Inhibiting tumor angiogenesis is a promising new strategy for treating cancer. Difficulties with the stability, manufacture, and long-term administration of recombinant antiangiogenic proteins have prompted investigators to use gene therapy to generate these proteins in vivo. We investigated whether transfer of the gene encoding the angiogenesis inhibitor endostatin into the murine liver cell line NMuLi could inhibit tumor growth in vivo. NMuLi cells were transduced with retroviral vectors containing the murine endostatin gene. The presence and function of endostatin in transduced cell supernatants were confirmed by competitive enzyme immunoassay and endothelial cell proliferation assays. Nude mice were given a subcutaneous or intraperitoneal injection with NMuLi cells, control transduced cells (NEF-null), or endostatin-transduced clones (NEF-Endol to 4) and were monitored for tumor growth. All statistical tests were two-sided. Supernatants from the clone secreting the lowest amount of endostatin (NEF-Endo4, 28 ng/mL) inhibited endothelial cell proliferation by 6% (95% confidence interval [CI] = 0% to 12%), and those from the clone secreting the highest amount (NEF-Endo1, 223 ng/mL) inhibited endothelial cell proliferation by 20% (95% CI = 13% to 27%). Increased levels of endostatin were detected in tumor lysates, but not serum, of mice given a subcutaneous injection of NEF-Endo1 cells. After 63 days, mice given a subcutaneous injection of parental NMuLi or NEF-null cells had tumor volumes of 2400 mm super(3) (95% CI = 1478 mm super(3) to 3300 mm super(3)) and 2700 mm super(3) (95% CI = 2241 mm super(3) to 3144 mm super(3)), respectively, compared with mean tumor volumes of less than 30 mm super(3) in mice given an injection of NEF-Endo clones, a statistically significant difference (P<.001). After 123 days, all 16 mice given an intraperitoneal injection of parental NMuLi or NEF-null cells had died, compared with only three (9%) of 32 mice given an injection of NEF-Endo clones. Retroviral endostatin gene transfer leads to secretion of functional endostatin that is sufficiently active to inhibit tumor growth. Further studies of retroviral endostatin gene transfer for the treatment of cancer are warranted. JF - Journal of the National Cancer Institute AU - Feldman, AL AU - Alexander, H R AU - Hewitt, S M AU - Lorang, D AU - Thiruvathukal, CE AU - Turner, E M AU - Libutti, S K AD - National Institutes of Health, Bldg. 10, Rm. 3C428, Bethesda, MD 20892, USA, Steven_Libutti@nih.gov Y1 - 2001/07/04/ PY - 2001 DA - 2001 Jul 04 SP - 1014 EP - 1020 VL - 93 IS - 13 SN - 0027-8874, 0027-8874 KW - mice KW - endostatin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Retrovirus KW - Gene therapy KW - Gene transfer KW - Tumors KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18175247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Effect+of+Retroviral+Endostatin+Gene+Transfer+on+Subcutaneous+and+Intraperitoneal+Growth+of+Murine+Tumors&rft.au=Feldman%2C+AL%3BAlexander%2C+H+R%3BHewitt%2C+S+M%3BLorang%2C+D%3BThiruvathukal%2C+CE%3BTurner%2C+E+M%3BLibutti%2C+S+K&rft.aulast=Feldman&rft.aufirst=AL&rft.date=2001-07-04&rft.volume=93&rft.issue=13&rft.spage=1014&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumors; Cancer; Expression vectors; Gene transfer; Retrovirus; Gene therapy ER - TY - JOUR T1 - Genetic demonstration of p47phox-dependent superoxide anion production in murine vascular smooth muscle cells. AN - 71011288; 11435342 AB - Previous investigations provide evidence that an enzyme related to the phagocyte NADPH oxidase produces superoxide in the blood vessel wall. These data, however, are confounded by observations that both NADPH and NADH serve as substrates for superoxide production in vascular cells. To clarify this issue, we compared the superoxide-generating capabilities of vascular smooth muscle cells (VSMCs) derived from wild-type (p47phox(+/+); phagocyte oxidase) mice with those from mice that lack p47phox (p47phox(-/-); "knockout"), an essential component of the phagocyte NADPH oxidase. VSMCs were derived from aortic explants harvested from p47phox(+/+) or p47phox(-/-) mice. VSMCs from p47phox(+/+) but not those from p47phox(-/-) mice produced superoxide after stimulation by phorbol myristate acetate. Consistent with this, p47phox was detected only in p47phox(+/+) VSMCs. p47phox-transduced p47phox(-/-) but not enhanced green fluorescent protein-transduced p47phox(-/-) VSMCs generated significant levels of superoxide after stimulation by angiotensin II or platelet-derived growth factor-BB (PDGF-BB). Enhanced expression of recombinant p47phox in p47phox-transduced p47phox(-/-) cells correlated with superoxide production in these cells. These data provide direct functional proof that an oxidase requiring the p47phox component mediates superoxide release from VSMCs in the blood vessel wall in response to angiotensin II or PDGF-BB. JF - Circulation AU - Lavigne, M C AU - Malech, H L AU - Holland, S M AU - Leto, T L AD - Laboratory of Host Defenses, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Md, USA. Y1 - 2001/07/03/ PY - 2001 DA - 2001 Jul 03 SP - 79 EP - 84 VL - 104 IS - 1 KW - Actins KW - 0 KW - Phosphoproteins KW - Platelet-Derived Growth Factor KW - Proto-Oncogene Proteins c-sis KW - Recombinant Proteins KW - Superoxides KW - 11062-77-4 KW - Angiotensin II KW - 11128-99-7 KW - becaplermin KW - 1B56C968OA KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - NADPH Oxidase -- metabolism KW - Animals KW - Microscopy, Phase-Contrast KW - Fluorescent Antibody Technique, Indirect KW - Aorta KW - Transduction, Genetic KW - Platelet-Derived Growth Factor -- pharmacology KW - Mice KW - Recombinant Proteins -- genetics KW - Angiotensin II -- pharmacology KW - Mice, Knockout KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Genes, Reporter KW - Mice, Inbred C57BL KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Retroviridae -- genetics KW - Actins -- biosynthesis KW - Female KW - Phosphoproteins -- deficiency KW - Superoxides -- metabolism KW - Phosphoproteins -- genetics KW - Muscle, Smooth, Vascular -- drug effects KW - Muscle, Smooth, Vascular -- cytology KW - Muscle, Smooth, Vascular -- metabolism KW - Granulomatous Disease, Chronic -- genetics KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71011288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Genetic+demonstration+of+p47phox-dependent+superoxide+anion+production+in+murine+vascular+smooth+muscle+cells.&rft.au=Lavigne%2C+M+C%3BMalech%2C+H+L%3BHolland%2C+S+M%3BLeto%2C+T+L&rft.aulast=Lavigne&rft.aufirst=M&rft.date=2001-07-03&rft.volume=104&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen protects against beta-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt. AN - 70990761; 11435923 AB - The cellular mechanisms underlying the neuroprotective effects of estrogen are only beginning to be elucidated. Here we examined the role of protein kinase B (Akt) activation in 17beta-estradiol (E2) inhibition of beta-amyloid peptide (31-35) (Abeta31-35)-induced neurotoxicity in cultured rat hippocampal neurons. Abeta31-35 (25-30 betaM) significantly decreased the total number of microtubule associated protein-2 positive cells (MAP2+). This decrease was significantly reversed by pre-treatment with 100 nM E2. Further, 100 nM E2 alone significantly increased the total number of protein kinase B and microtubule associated protein-2 positive cells compared with controls. Such E2-induced increases were inhibited by LY294002 (20 microM), a specific PI3-K inhibitor, as well as by tamoxifen, an estrogen receptor antagonist/selective estrogen receptor modulator. These results indicate that the neuroprotective effects of E2 may be mediated at least in part via estrogen receptor-mediated protein kinase B activation. JF - Neuroreport AU - Zhang, L AU - Rubinow, D R AU - Xaing , G AU - Li, B S AU - Chang, Y H AU - Maric, D AU - Barker, J L AU - Ma, W AD - Behavioral Endocrinology Branch NIMH, Building 10, Room 3N238, NIH, Bethesda, MD 20892, USA. Y1 - 2001/07/03/ PY - 2001 DA - 2001 Jul 03 SP - 1919 EP - 1923 VL - 12 IS - 9 SN - 0959-4965, 0959-4965 KW - Amyloid beta-Peptides KW - 0 KW - Chromones KW - Enzyme Inhibitors KW - Estrogen Antagonists KW - Microtubule-Associated Proteins KW - Morpholines KW - Neuroprotective Agents KW - Neurotoxins KW - Peptide Fragments KW - Proto-Oncogene Proteins KW - Receptors, Estrogen KW - amyloid beta-protein (31-35) KW - Tamoxifen KW - 094ZI81Y45 KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Estradiol KW - 4TI98Z838E KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Animals KW - Fetus KW - Microtubule-Associated Proteins -- metabolism KW - Receptors, Estrogen -- drug effects KW - Alzheimer Disease -- drug therapy KW - Cells, Cultured -- drug effects KW - Cells, Cultured -- cytology KW - Rats KW - Estrogen Antagonists -- pharmacology KW - Chromones -- pharmacology KW - Cell Survival -- drug effects KW - Alzheimer Disease -- metabolism KW - Tamoxifen -- pharmacology KW - Cell Count KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Alzheimer Disease -- physiopathology KW - Morpholines -- pharmacology KW - Receptors, Estrogen -- metabolism KW - Drug Interactions -- physiology KW - Cells, Cultured -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Immunohistochemistry KW - Cell Survival -- physiology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Peptide Fragments -- metabolism KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Estradiol -- pharmacology KW - Hippocampus -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Neurotoxins -- pharmacology KW - Estradiol -- metabolism KW - Hippocampus -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Proto-Oncogene Proteins -- drug effects KW - Amyloid beta-Peptides -- metabolism KW - Peptide Fragments -- pharmacology KW - Amyloid beta-Peptides -- pharmacology KW - Hippocampus -- cytology KW - Neurons -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70990761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Estrogen+protects+against+beta-amyloid-induced+neurotoxicity+in+rat+hippocampal+neurons+by+activation+of+Akt.&rft.au=Zhang%2C+L%3BRubinow%2C+D+R%3BXaing+%2C+G%3BLi%2C+B+S%3BChang%2C+Y+H%3BMaric%2C+D%3BBarker%2C+J+L%3BMa%2C+W&rft.aulast=Zhang&rft.aufirst=L&rft.date=2001-07-03&rft.volume=12&rft.issue=9&rft.spage=1919&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic fidelity under harsh conditions: Analysis of spontaneous mutation in the thermoacidophilic archaeon Sulfolobus acidocaldarius AN - 18076822; 5144146 AB - Microbes whose genomes are encoded by DNA and for which adequate information is available display similar genomic mutation rates (average 0.0034 mutations per chromosome replication, range 0.0025 to 0.0046). However, this value currently is based on only a few well characterized microbes reproducing within a narrow range of environmental conditions. In particular, no genomic mutation rate has been determined either for a microbe whose natural growth conditions may extensively damage DNA or for any member of the archaea, a prokaryotic lineage deeply diverged from both bacteria and eukaryotes. Both of these conditions are met by the extreme thermoacidophile Sulfolobus acidocaldarius. We determined the genomic mutation rate for this species when growing at pH 3.5 and 75 degree C based on the rate of forward mutation at the pyrE gene and the nucleotide changes identified in 101 independent mutants. The observed value of about 0.0018 extends the range of DNA-based microbes with rates close to the standard rate simultaneously to an archaeon and to an extremophile whose cytoplasmic pH and normal growth temperature greatly accelerate the spontaneous decomposition of DNA. The mutations include base pair substitutions (BPSs) and additions and deletions of various sizes, but the S. acidocaldarius spectrum differs from those of other DNA-based organisms in being relatively poor in BPSs. The paucity of BPSs cannot yet be explained by known properties of DNA replication or repair enzymes of Sulfolobus spp. It suggests, however, that molecular evolution per genome replication may proceed more slowly in S. acidocaldarius than in other DNA-based organisms examined to date. JF - Proceedings of the National Academy of Sciences, USA AU - Grogan, D W AU - Carver, G T AU - Drake, J W AD - Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 45221-0006, drake@niehs.nih.gov Y1 - 2001/07/03/ PY - 2001 DA - 2001 Jul 03 SP - 7928 EP - 7933 VL - 98 IS - 14 SN - 0027-8424, 0027-8424 KW - Mutation rates KW - Thermophilic archaea KW - acidophilic archaea KW - pyrE gene KW - Oceanic Abstracts; ASFA 1: Biological Sciences & Living Resources; Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Genomes KW - Marine KW - Mutations KW - Sulfolobus acidocaldarius KW - DNA damage KW - Genetics KW - Fidelity KW - Microbiology KW - Microorganisms KW - DNA KW - O 1010:Viruses, Bacteria, Protists, Fungi and Plants KW - G 07320:Bacterial genetics KW - Q1 08245:Genetics and evolution KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18076822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Genetic+fidelity+under+harsh+conditions%3A+Analysis+of+spontaneous+mutation+in+the+thermoacidophilic+archaeon+Sulfolobus+acidocaldarius&rft.au=Grogan%2C+D+W%3BCarver%2C+G+T%3BDrake%2C+J+W&rft.aulast=Grogan&rft.aufirst=D&rft.date=2001-07-03&rft.volume=98&rft.issue=14&rft.spage=7928&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.141113098 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Genomes; Genetics; Mutations; Microbiology; DNA; Microorganisms; Temperature effects; DNA damage; Fidelity; Thermophilic archaea; Mutation rates; Sulfolobus acidocaldarius; Marine DO - http://dx.doi.org/10.1073/pnas.141113098 ER - TY - JOUR T1 - Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages. AN - 70965252; 11431009 AB - We sought to identify neurotoxin(s) secreted by HIV-1-infected mononuclear phagocytes that could contribute to the pathophysiology of HIV-1-associated dementia (HAD). Neurotoxic factors were characterized in batches of conditioned media (CM) from human monocyte-derived macrophages (MDM) infected with HIV-1(ADA) and/or activated with lipopolysaccharide (LPS). All of the neurotoxicity was: present in the <3000-Da fraction; blocked by 5 microM MK801; and not trypsin sensitive or extractable into polar organic solvents. Glutamate measured in CM accounted for all neurotoxic effects observed from HIV/LPS CM in astrocyte-poor neuronal cultures and may contribute to the pathophysiology of HIV-1-associated dementia. JF - Journal of neuroimmunology AU - Jiang, Z G AU - Piggee, C AU - Heyes, M P AU - Murphy, C AU - Quearry, B AU - Bauer, M AU - Zheng, J AU - Gendelman, H E AU - Markey, S P AD - Laboratory of Neurotoxicology, NIMH, 10 Center Drive, Room 3D42, NIH, 20892-1262, Bethesda, MD, USA. Y1 - 2001/07/02/ PY - 2001 DA - 2001 Jul 02 SP - 97 EP - 107 VL - 117 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Lipopolysaccharides KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Rats KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Cells, Cultured KW - Humans KW - Lipopolysaccharides -- toxicity KW - Trypsin -- pharmacology KW - Macrophages -- secretion KW - Glutamic Acid -- toxicity KW - HIV-1 -- pathogenicity KW - AIDS Dementia Complex -- etiology KW - Macrophage Activation KW - Macrophages -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70965252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroimmunology&rft.atitle=Glutamate+is+a+mediator+of+neurotoxicity+in+secretions+of+activated+HIV-1-infected+macrophages.&rft.au=Jiang%2C+Z+G%3BPiggee%2C+C%3BHeyes%2C+M+P%3BMurphy%2C+C%3BQuearry%2C+B%3BBauer%2C+M%3BZheng%2C+J%3BGendelman%2C+H+E%3BMarkey%2C+S+P&rft.aulast=Jiang&rft.aufirst=Z&rft.date=2001-07-02&rft.volume=117&rft.issue=1-2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress in zebrafish cells: Potential utility of transgenic zebrafish as a deployable sentinel for site hazard ranking AN - 18345533; 5171335 AB - In order to quickly assess potential environmental hazards of forwardly deployed military bases, we have focussed our efforts on biochemical and molecular changes in vertebrate cells following exposure to aqueous soil extracts. To this end, we are designing a series of deployable transgenic fish. Fish exhibit many of the same general defenses against toxic chemicals as do mammals, including enzyme induction, and the generation of oxidative stress. In response to many foreign compounds that generate oxidative stress, the transcription of certain protective genes is induced via specific DNA motifs called electrophile response elements (EPREs). We have made a plasmid construct containing a single murine EPRE fused to a minimal promoter and the cDNA encoding firefly luciferase (EPRE-LUC). In this paper, we have shown that the treatment of zebrafish cell line ZEM2S with a variety of chemicals known to induce EPRE-dependent transcription in cultured mammalian cells, results in dose-dependent induction of the transiently-transfected EPRE-LUC reporter construct. Compounds tested include aromatic hydrocarbons, heavy metals, and organophosphates. We observed similar dose-dependent responses when we treated ZEM2S and human cells in vitro with identical aqueous extracts of soil from hazardous waste sites. This suggests that the mechanism by which these compounds activate transcription is well conserved between mammals and zebrafish, and that transgenic zebrafish lines containing EPRE-driven reporter constructs might be useful as sentinels for the early detection of oxidative stress-inducing chemicals. JF - Science of the Total Environment AU - Carvan, MJ III AU - Sonntag, D M AU - Cmar, C B AU - Cook, R S AU - Curran, MA AU - Miller, G L AD - Great Lakes WATER Institute and NIEHS Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee, 600 East Greenfield Avenue, Milwaukee, WI 53204, USA, carvanmj@uwm.edu Y1 - 2001/07/02/ PY - 2001 DA - 2001 Jul 02 SP - 183 EP - 196 VL - 274 IS - 1-3 SN - 0048-9697, 0048-9697 KW - Zebra danio KW - aromatic hydrocarbons KW - cell culture KW - dose-response effects KW - organophosphorus compounds KW - Pollution Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Toxicology Abstracts; Risk Abstracts; Aqualine Abstracts; Water Resources Abstracts KW - Chemicals KW - Aquatic organisms KW - Pollution monitoring KW - Biological stress KW - Organophosphates KW - Heavy metals KW - Pollution effects KW - Cell culture KW - Toxicity tests KW - Pisces KW - Transgenic animals KW - Oxidative stress KW - Waste disposal sites KW - Animals (Vertebrates) (see also Individual groups) KW - Aromatic hydrocarbons KW - Chemical pollution KW - Military KW - Pollution indicators KW - Bioindicators KW - Hydrocarbons KW - Fish (see also Individual groups) KW - Enzymes KW - Toxicity KW - Soil contamination KW - Fish Physiology KW - Danio rerio KW - Cytotoxicity KW - Bioassays KW - Water Pollution Effects KW - Oxidation KW - DNA KW - Toxicity (see also Lethal limits) KW - Toxicity testing KW - Indicator species KW - R2 23040:Biological KW - Q1 08346:Physiology, biochemistry, biophysics KW - P 5000:LAND POLLUTION KW - Q5 08504:Effects on organisms KW - SW 3030:Effects of pollution KW - AQ 00008:Effects of Pollution KW - X 24221:Toxicity testing KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18345533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+of+the+Total+Environment&rft.atitle=Oxidative+stress+in+zebrafish+cells%3A+Potential+utility+of+transgenic+zebrafish+as+a+deployable+sentinel+for+site+hazard+ranking&rft.au=Carvan%2C+MJ+III%3BSonntag%2C+D+M%3BCmar%2C+C+B%3BCook%2C+R+S%3BCurran%2C+MA%3BMiller%2C+G+L&rft.aulast=Carvan&rft.aufirst=MJ&rft.date=2001-07-02&rft.volume=274&rft.issue=1-3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Science+of+the+Total+Environment&rft.issn=00489697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Thematic Issue: Toxicology and Risk Assessment Approaches. N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Biological stress; Bioassays; Heavy metals; Waste disposal sites; Oxidation; Pollution effects; Aromatic hydrocarbons; Cell culture; Pollution indicators; Toxicity tests; Indicator species; Transgenic animals; Oxidative stress; Hydrocarbons; Toxicity testing; Pisces; Bioindicators; Pollution monitoring; Aquatic organisms; Cytotoxicity; Organophosphates; Soil contamination; Chemical pollution; Military; Chemicals; Fish (see also Individual groups); DNA; Animals (Vertebrates) (see also Individual groups); Toxicity (see also Lethal limits); Water Pollution Effects; Enzymes; Toxicity; Fish Physiology; Danio rerio ER - TY - JOUR T1 - Plasma membrane Ca2+-ATPase isoform 2a is the PMCA of hair bundles. AN - 85286961; pmid-11438582 AB - Mechanoelectrical transduction channels of hair cells allow for the entry of appreciable amounts of Ca(2+), which regulates adaptation and triggers the mechanical activity of hair bundles. Most Ca(2+) that enters transduction channels is extruded by the plasma membrane Ca(2+)-ATPase (PMCA), a Ca(2+) pump that is highly concentrated in hair bundles and may be essential for normal hair cell function. Because PMCA isozymes and splice forms are regulated differentially and have distinct biochemical properties, we determined the identity of hair bundle PMCA in frog and rat hair cells. By screening a bullfrog saccular cDNA library, we identified abundant PMCA1b and PMCA2a clones as well as rare PMCA2b and PMCA2c clones. Using immunocytochemistry and immunoprecipitation experiments, we showed in bullfrog sacculus that PMCA1b is the major isozyme of hair cell and supporting cell basolateral membranes and that PMCA2a is the only PMCA present in hair bundles. This complete segregation of PMCA1 and PMCA2 isozymes holds for rat auditory and vestibular hair cells; PMCA2a is the only PMCA isoform in hair bundles of outer hair cells and vestibular hair cells and is the predominant PMCA of hair bundles of inner hair cells. Our data suggest that hair cells control plasma membrane Ca(2+)-pumping activity by targeting specific PMCA isozymes to distinct subcellular locations. Because PMCA2a is the only Ca(2+) pump present at appreciable levels in hair bundles, the biochemical properties of this pump must account fully for the physiological features of transmembrane Ca(2+) pumping in bundles. JF - The Journal of Neuroscience AU - Dumont, R A AU - Lins, U AU - Filoteo, A G AU - Penniston, J T AU - Kachar Bechara AU - Gillespie, P G AD - Department of Physiology, Johns Hopkins University, Baltimore, Maryland 21205, USA.; National Institute on Deafness and Other Communication Disorders PY - 2001 SP - 5066 EP - 5078 VL - 21 IS - 14 SN - 0270-6474, 0270-6474 KW - Saccule and Utricle KW - Animals KW - Calcium KW - Hair Cells KW - Ca(2+)-Transporting ATPase KW - Sequence Analysis, DNA KW - Precipitin Tests KW - Organ of Corti KW - Cilia KW - Cloning, Molecular KW - Research Support, U.S. Gov't, P.H.S. KW - Rats KW - DNA, Complementary KW - Hair Cells, Vestibular KW - Alternative Splicing KW - Rana catesbeiana KW - Isoenzymes KW - Cell Membrane KW - Molecular Sequence Data KW - Microscopy, Immunoelectron KW - Sequence Homology, Amino Acid KW - Immunohistochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85286961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=Plasma+membrane+Ca2%2B-ATPase+isoform+2a+is+the+PMCA+of+hair+bundles.&rft.au=Dumont%2C+R+A%3BLins%2C+U%3BFiloteo%2C+A+G%3BPenniston%2C+J+T%3BKachar+Bechara%3BGillespie%2C+P+G&rft.aulast=Dumont&rft.aufirst=R&rft.date=2001-07-01&rft.volume=21&rft.issue=14&rft.spage=5066&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Relative risk for cognitive impairments in siblings of patients with schizophrenia. AN - 85250772; pmid-11527000 AB - BACKGROUND: Patients with schizophrenia have impairments in several domains of cognition, including working memory/executive function, verbal memory, language, oculomotor scanning/psychomotor speed, and general intelligence. Impairments have also been found in unaffected siblings, suggesting they could be heritable. To assess the suitability of cognitive dysfunction for use in genetic studies, we estimated relative risk (lambda) in a large cohort of siblings. METHODS: One hundred forty-seven patients with schizophrenia, 193 of their siblings, and 47 control subjects were studied using a neuropsychological test battery, which included intelligence quotient (IQ), Wide Range Achievement Test, Wisconsin Card Sort, Wechsler Memory Scale (revised), California Verbal List Test, Trails A and B, and Letter and Category Fluency. Relative risk was estimated using a cutoff score of 1 SD below the control mean. RESULTS: As expected, patients performed markedly worse than control subjects on all tests except the Wide Range Achievement Test. Siblings had impaired performance on the Wisconsin Card Sort and Trails B, with trends for reduction (p = .01-.05) on the California Verbal List Test and Letter Fluency. Relative risk to siblings was elevated on the Trails B (lambda = 4.0) and California Verbal List Test (lambda = 2.8). Trends (p = .01-.05) for increased lambda were also seen for Wisconsin Card Sort, Letter Fluency, Wechsler Memory Scale and decline in IQ (lambda = 1.74-2.4). Correlations between tests of different cognitive functions were weak, indicating they measure relatively independent processes. CONCLUSION: Unselected siblings of patients with schizophrenia have impairments in several cognitive domains. Relative risk scores were in the moderate range, suggesting a significant genetic component. Impairments on one test only weakly predicted impairments on other tests. Thus, cognitive phenotypes identify distinct, familial traits associated with schizophrenia. Using this dimensional approach to subdividing schizophrenia may reduce the clinical and genetic heterogeneity of schizophrenia and improve the power of genetic studies. JF - Biological Psychiatry AU - Egan, M F AU - Goldberg, T E AU - Gscheidle, T AU - Weirich, M AU - Rawlings, R AU - Hyde, T M AU - Bigelow, L AU - Weinberger, D R AD - Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2001 SP - 98 EP - 107 VL - 50 IS - 2 SN - 0006-3223, 0006-3223 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Nuclear Family KW - Cognition Disorders KW - Phenotype KW - Schizophrenia KW - Memory KW - Comparative Study KW - Risk Factors KW - Adult KW - Support, Non-U.S. Gov't KW - Neuropsychological Tests KW - Male KW - Female KW - Schizophrenic Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85250772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Psychiatry&rft.atitle=Relative+risk+for+cognitive+impairments+in+siblings+of+patients+with+schizophrenia.&rft.au=Egan%2C+M+F%3BGoldberg%2C+T+E%3BGscheidle%2C+T%3BWeirich%2C+M%3BRawlings%2C+R%3BHyde%2C+T+M%3BBigelow%2C+L%3BWeinberger%2C+D+R&rft.aulast=Egan&rft.aufirst=M&rft.date=2001-07-01&rft.volume=50&rft.issue=2&rft.spage=98&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Reactive oxygen species and signal transduction. AN - 72399156; 11795590 AB - Increasing evidence suggests a role for intracellular reactive oxygen species (ROS) as mediators of normal and pathological signal transduction pathways. In particular, a growing list of recent reports have demonstrated a rapid and significant increases in intracellular ROS following growth factor or cytokine stimulation. These ROS appear essential for a host of downstream signaling events. Biochemical characterization of this ligand-activated ROS production has revealed important information regarding the molecular composition of the cellular oxidases and the regulation of their activity by small GTPases. Work is proceeding on identifying strategies to identify how ROS might specifically regulate signaling pathways by altering the activity of direct target molecules. This review will focus on the progress in the rapid emerging area of oxidant or redox-dependent signal transduction and speculate how these insights might alter our view and treatment of diseases thought to be caused by oxidative stress. JF - IUBMB life AU - Finkel, T AD - Laboratory of Molecular Biology, NHLBI, NIH, Bethesda, MD 20814-1622, USA. finkelt@nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 3 EP - 6 VL - 52 IS - 1-2 SN - 1521-6543, 1521-6543 KW - Growth Substances KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Oxidation-Reduction -- drug effects KW - Growth Substances -- pharmacology KW - GTP Phosphohydrolases -- metabolism KW - Oxidative Stress -- drug effects KW - Oxidants -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Signal Transduction -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72399156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IUBMB+life&rft.atitle=Reactive+oxygen+species+and+signal+transduction.&rft.au=Finkel%2C+T&rft.aulast=Finkel&rft.aufirst=T&rft.date=2001-07-01&rft.volume=52&rft.issue=1-2&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=IUBMB+life&rft.issn=15216543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-25 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Return of immigrants: a cluster analysis of mesotheliomas among residents of the Veneto region who used to work at the ETERNIT AG factory at Niederurnen, Switzerland]. TT - Emigrazione di ritorno: un cluster di mesoteliomi in Veneto tra ex-lavoratori della Eternit AG di Niederurnen, Svizzera. AN - 72398150; 11789455 AB - We identified 5 mesotheliomas among Italian migrant workers who returned home and settled in the Veneto Region, after employment at the ETERNIT AG factory in Switzerland. During the 1970s the factory employed about 1000 workers and the presence of Italian migrants was relevant. The cluster confirms that migration for work has caused exposures to carcinogenic substances and confirms that neoplastic diseases are occurring among those resettled in Italy and helps explaining the high occurrence of mesotheliomas in this country. JF - Epidemiologia e prevenzione AU - Merler, E AU - Gioffré, F AU - Mabilia, T AU - De Marzio, N AU - Bizzotto, R AU - Sarto, F AU - Zambon, P AD - Servizio di prevenzione Igiene e sicurezza nei luoghi lavoro, ULSS 16, Padova. PY - 2001 SP - 161 EP - 163 VL - 25 IS - 4-5 SN - 1120-9763, 1120-9763 KW - Index Medicus KW - Italy -- ethnology KW - Switzerland -- epidemiology KW - Humans KW - Italy -- epidemiology KW - Cluster Analysis KW - Male KW - Female KW - Catchment Area (Health) KW - Occupational Diseases -- ethnology KW - Mesothelioma -- ethnology KW - Emigration and Immigration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72398150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologia+e+prevenzione&rft.atitle=%5BReturn+of+immigrants%3A+a+cluster+analysis+of+mesotheliomas+among+residents+of+the+Veneto+region+who+used+to+work+at+the+ETERNIT+AG+factory+at+Niederurnen%2C+Switzerland%5D.&rft.au=Merler%2C+E%3BGioffr%C3%A9%2C+F%3BMabilia%2C+T%3BDe+Marzio%2C+N%3BBizzotto%2C+R%3BSarto%2C+F%3BZambon%2C+P&rft.aulast=Merler&rft.aufirst=E&rft.date=2001-07-01&rft.volume=25&rft.issue=4-5&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Epidemiologia+e+prevenzione&rft.issn=11209763&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2002-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder cancer. AN - 72246377; 11693804 AB - An association between human papilloma virus (HPV) and bladder cancer has been reported. However, the role of HPV in bilharzial bladder cancer and its prevalence have not yet been clarified. We investigated 50 cases for HPV types 16/18 by in situ hybridization. Also, p53 protein expression by immunohistochemistry was evaluated in 41 of the 50 cases, with correlation of these factors to clinicopathologic parameters and tumor relapse after primary treatment. HPV was detected in 46% of Egyptian bladder carcinomas (23/50 cases). Positivity was 47.8% for squamous cell carcinoma and 36.4% for transitional cell carcinoma. There was a possible viral-bilharzial association as 52.8% of Bilharzial cases, whereas only 12.5% of non-Bilharzial cases were HPV positive (P <0.05). P53 protein was found in 19/41 (46.3%) cases. There was a concordance between HPV and p53 in 58.5% of cases. Neither factor was related to tumor recurrence after primary treatment. HPV may thus be implicated in the etiology of bilharzial bladder cancer, but a definite causal relationship remains to be demonstrated. HPV together with p53 alterations work in synergy to accelerate the carcinogenic process, as there was concordance in the results of both parameters in 24/41 (58.5%) cases. JF - Tumori AU - Khaled, H M AU - Raafat, A AU - Mokhtar, N AU - Zekri, A R AU - Gaballah, H AD - Department of Medical Oncology, National Cancer Institute, Cairo University, Egypt. PY - 2001 SP - 256 EP - 261 VL - 87 IS - 4 SN - 0300-8916, 0300-8916 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Carcinoma, Transitional Cell -- complications KW - Humans KW - Carcinoma, Squamous Cell -- complications KW - Aged KW - Carcinoma, Squamous Cell -- metabolism KW - Carcinoma, Transitional Cell -- metabolism KW - Carcinoma, Transitional Cell -- virology KW - Carcinoma, Squamous Cell -- virology KW - In Situ Hybridization KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Papillomavirus Infections -- complications KW - Papillomaviridae -- isolation & purification KW - Schistosomiasis -- complications KW - Papillomavirus Infections -- virology KW - Urinary Bladder Neoplasms -- virology KW - Urinary Bladder Neoplasms -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Urinary Bladder Neoplasms -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72246377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Human+papilloma+virus+infection+and+overexpression+of+p53+protein+in+bilharzial+bladder+cancer.&rft.au=Khaled%2C+H+M%3BRaafat%2C+A%3BMokhtar%2C+N%3BZekri%2C+A+R%3BGaballah%2C+H&rft.aulast=Khaled&rft.aufirst=H&rft.date=2001-07-01&rft.volume=87&rft.issue=4&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sphincter-preserving procedures: the experience of the National Cancer Institute of Milan. AN - 72246181; 11693815 JF - Tumori AU - Leo, E AU - Andreola, S AU - Belli, F AU - Bonfanti, G AU - Gallino, G AU - Vitellaro, M AU - Battaglia, L AU - Valvo, F AD - Colorectal Surgery Unit, National Cancer Institute, Milan, Italy. info@areco.it PY - 2001 SP - S28 EP - S30 VL - 87 IS - 4 SN - 0300-8916, 0300-8916 KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Treatment Outcome KW - Neoplasm Recurrence, Local KW - Italy KW - Fluorouracil -- therapeutic use KW - Rectal Neoplasms -- drug therapy KW - Rectal Neoplasms -- surgery KW - Rectal Neoplasms -- radiotherapy KW - Anal Canal -- surgery KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72246181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Sphincter-preserving+procedures%3A+the+experience+of+the+National+Cancer+Institute+of+Milan.&rft.au=Leo%2C+E%3BAndreola%2C+S%3BBelli%2C+F%3BBonfanti%2C+G%3BGallino%2C+G%3BVitellaro%2C+M%3BBattaglia%2C+L%3BValvo%2C+F&rft.aulast=Leo&rft.aufirst=E&rft.date=2001-07-01&rft.volume=87&rft.issue=4&rft.spage=S28&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VIP receptor antagonists and chemotherapeutic drugs inhibit the growth of breast cancer cells. AN - 72229117; 11678309 AB - The effects of vasoactive intestinal peptide (VIP) antagonists on breast cancer cells were investigated. (N-stearyl, norleucine17)VIP hybrid ((SN)VIPhyb) inhibited specific 125I-VIP binding to MCF7, SKBR3, T47D ZR75-1 and MDA-MB231 cells with high affinity (IC50 values of 0.03-0.06 microM). (SN)VIPhyb, 1 microM, inhibited the ability of 10 nM VIP to cause elevation of cAMP and to increase c-fos mRNA. Micromolar concentrations of (SN)VIPhyb inhibited the proliferation of MDA-MB231 or MCF7 cells using a MTT and clonogenic assay. Using a MTT assay, (SN)VIPhyb enhanced the ability of taxol and doxorubicin to inhibit breast cancer growth. Using nude mice bearing MDA-MB231 xenografts, VIPhyb potentiated the ability of taxol to inhibit proliferation. The results indicate that VIP receptor antagonists increase the ability of chemotherapeutic drugs to kill breast cancer cells. JF - Breast cancer research and treatment AU - Moody, T W AU - Leyton, J AU - Chan, D AU - Brenneman, D C AU - Fridkin, M AU - Gelber, E AU - Levy, A AU - Gozes, I AD - Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 55 EP - 64 VL - 68 IS - 1 SN - 0167-6806, 0167-6806 KW - Antineoplastic Agents KW - 0 KW - Iodine Radioisotopes KW - RNA, Messenger KW - Receptors, Vasoactive Intestinal Peptide KW - Recombinant Fusion Proteins KW - stearyl-norleucine(17)-vasoactive intestinal peptide KW - (VIP-neurotensin) hybrid antagonist KW - 125093-93-8 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Neurotensin KW - 39379-15-2 KW - Doxorubicin KW - 80168379AG KW - Cyclic AMP KW - E0399OZS9N KW - Paclitaxel KW - P88XT4IS4D KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - RNA, Messenger -- drug effects KW - Cell Division -- drug effects KW - Disease Models, Animal KW - Paclitaxel -- pharmacology KW - Mice, Nude KW - Amino Acid Sequence KW - Mice KW - Genes, fos -- drug effects KW - Mice, Inbred BALB C KW - Doxorubicin -- pharmacology KW - Protein Binding -- drug effects KW - Molecular Sequence Data KW - Cyclic AMP -- metabolism KW - Transplantation, Heterologous KW - Drug Synergism KW - Female KW - Vasoactive Intestinal Peptide -- pharmacology KW - Breast Neoplasms -- drug therapy KW - Neurotensin -- pharmacology KW - Vasoactive Intestinal Peptide -- metabolism KW - Receptors, Vasoactive Intestinal Peptide -- metabolism KW - Vasoactive Intestinal Peptide -- chemistry KW - Neurotensin -- therapeutic use KW - Vasoactive Intestinal Peptide -- therapeutic use KW - Vasoactive Intestinal Peptide -- antagonists & inhibitors KW - Recombinant Fusion Proteins -- pharmacology KW - Receptors, Vasoactive Intestinal Peptide -- antagonists & inhibitors KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Recombinant Fusion Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72229117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=VIP+receptor+antagonists+and+chemotherapeutic+drugs+inhibit+the+growth+of+breast+cancer+cells.&rft.au=Moody%2C+T+W%3BLeyton%2C+J%3BChan%2C+D%3BBrenneman%2C+D+C%3BFridkin%2C+M%3BGelber%2C+E%3BLevy%2C+A%3BGozes%2C+I&rft.aulast=Moody&rft.aufirst=T&rft.date=2001-07-01&rft.volume=68&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-19 N1 - Date created - 2001-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for adolescent substance abuse. AN - 71378571; 15503578 AB - Reviews research on risk factors for adolescent substance use disorders (SUD) and discusses possible relationships between SUDs and learning disabilities (LD). Individual level factors (genetic, biologic, other familial, and psychiatric) emerge as very important in the risk equation, as well as the interaction between individual risk and environmental conditions. Commonalities between SUD risk and LD include prenatal substance exposure, family history of SUD, conduct disorder, social skills deficits, and academic failure; however, further research is needed to establish whether individuals with LD face a specific risk for SUDs, and if so, what the nature of that risk might be. JF - Journal of learning disabilities AU - Weinberg, N Z AD - Division of Epidemiology, Services, and Prevention Research, National Institute of Drug Abuse, National Institutes of Health, Bethesda, MD 20892-9589, USA. PY - 2001 SP - 343 EP - 351 VL - 34 IS - 4 SN - 0022-2194, 0022-2194 KW - Index Medicus KW - Intelligence KW - Educational Status KW - Risk Factors KW - Humans KW - Follow-Up Studies KW - Child KW - Adolescent KW - Male KW - Female KW - Comorbidity KW - Child, Preschool KW - Learning Disorders -- epidemiology KW - Attention Deficit Disorder with Hyperactivity -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71378571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+learning+disabilities&rft.atitle=Risk+factors+for+adolescent+substance+abuse.&rft.au=Weinberg%2C+N+Z&rft.aulast=Weinberg&rft.aufirst=N&rft.date=2001-07-01&rft.volume=34&rft.issue=4&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Journal+of+learning+disabilities&rft.issn=00222194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-01 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biological indicators for the identification of ionizing radiation exposure in humans. AN - 71294593; 11901816 AB - While the effects of acute high-dose irradiation are well-documented, less is known about the effects of low level chronic radiation exposure. Physical dosimetry cannot always be relied upon, so dose estimates and determination of past radiation exposure must often be based upon biological indicators. Some of the established methods used in the assessment of nuclear accidents are reviewed here, including cytogenetic analyses, mutation-based assays and electron spin resonance. As interest in research on low-level radiation exposures expands, there is an increasing need for new biomarkers that can identify exposed individuals in human populations. Developments in high-throughput gene expression profiling may enable future development of a rapid and noninvasive testing method for application to potentially exposed populations. JF - Expert review of molecular diagnostics AU - Amundson, S A AU - Bittner, M AU - Meltzer, P AU - Trent, J AU - Fornace, A J AD - NIH, National Cancer Institute, 37 Convent Dr., Bldg. 37, Bethesda, MD 20892, USA. amundson@mail.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 211 EP - 219 VL - 1 IS - 2 SN - 1473-7159, 1473-7159 KW - Biomarkers KW - 0 KW - Index Medicus KW - Occupational Exposure KW - Radiation Dosage KW - Micronucleus Tests KW - Oligonucleotide Array Sequence Analysis KW - Models, Genetic KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Molecular Diagnostic Techniques KW - Chromosome Aberrations KW - Mutation KW - Radiation Injuries KW - Chromosomes -- radiation effects KW - Radiometry KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71294593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+review+of+molecular+diagnostics&rft.atitle=Biological+indicators+for+the+identification+of+ionizing+radiation+exposure+in+humans.&rft.au=Amundson%2C+S+A%3BBittner%2C+M%3BMeltzer%2C+P%3BTrent%2C+J%3BFornace%2C+A+J&rft.aulast=Amundson&rft.aufirst=S&rft.date=2001-07-01&rft.volume=1&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+molecular+diagnostics&rft.issn=14737159&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-12 N1 - Date created - 2002-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Guidelines for the safe administration of high-dose interleukin-2. AN - 71182554; 11565830 AB - High-dose interleukin-2 (IL-2) results in objective clinical regression of metastatic cancer in 15% to 17% of patients with melanoma and renal cell carcinoma. Durable complete regression of all metastases is seen in 6% to 8% of patients. Based on these findings, the U.S. Food and Drug Administration has approved the use of high-dose IL-2 for the treatment of patients with metastatic melanoma and renal cell carcinoma. Interleukin-2 administration is associated with many different side effects, and after many years of use, clinicians have learned how to safely administer high-dose IL-2. This article details practical guidelines for the safe administration of high-dose IL-2. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Schwartzentruber, D J AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. djs@nih.gov PY - 2001 SP - 287 EP - 293 VL - 24 IS - 4 SN - 1524-9557, 1524-9557 KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Fluid Therapy KW - Drug Administration Schedule KW - Pleural Effusion -- therapy KW - Humans KW - Hypotension -- therapy KW - Hypotension -- etiology KW - Capillary Leak Syndrome -- chemically induced KW - Pleural Effusion -- chemically induced KW - Capillary Leak Syndrome -- diagnosis KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Melanoma -- secondary KW - Interleukin-2 -- therapeutic use KW - Melanoma -- drug therapy KW - Carcinoma, Renal Cell -- secondary KW - Carcinoma, Renal Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71182554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Guidelines+for+the+safe+administration+of+high-dose+interleukin-2.&rft.au=Schwartzentruber%2C+D+J&rft.aulast=Schwartzentruber&rft.aufirst=D&rft.date=2001-07-01&rft.volume=24&rft.issue=4&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-08 N1 - Date created - 2001-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unique renal tubule changes induced in rats and mice by the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D) and WY-14643. AN - 71175663; 11560249 AB - Peroxisome proliferators are non-mutagenic carcinogens in the liver of rodents, acting both as initiators and promoters. The National Toxicology Program (NTP) conducted a study of several peroxisome proliferators (PPs), including Wyeth (WY)-14643 as a prototypical PP and 2,4-dichlorophenoxyacetic acid (2,4-D) as a weak PP, in Sprague-Dawley rats. B6C3F1 mice, and Syrian hamsters. In the kidney, an unusual change was observed in the outer stripe of the outer medulla, especially in rats treated with 2,4-D or WY-14643. This change was characterized by foci of tubules that were partially or completely lined by basophilic epithelial cells with decreased cytoplasm and high nuclear density. Changes typical of chronic nephropathy such as interstitial fibrosis or basement membrane thickening were not associated with these foci. Results of immunohistochemical staining for catalase and cytochrome P-450 4A in the kidney indicated increased staining intensity in renal tubular epithelial cells primarily in the region where the affected tubules were observed: however, the altered cells were negative for both immunohistochemical markers. Ultrastructurally, affected cells had long brush borders typical of the P3 tubule segment. The most distinguishing ultrastructural change was a decreased amount of electronlucent cytoplasm that contained few differentiated organelles and, in particular, a prominent reduced volume and number of mitochondria; changes in peroxisomes were not apparent. In addition to the lesion in rats, mice treated with the highest dose of 2,4-D, but not WY-14643, manifested similar renal tubular changes as seen by light microscopy. Neither chemical induced renal tubular lesions in hamsters. Hepatocellular changes characteristic of PPs were present in all 3 species treated with WY-14643, but not 2,4-D. These results indicate that the rat is the species most sensitive to the nephrotoxic effects of PPs and there is a site specificity to this toxicity related to areas of PP-related enzyme induction. Although 2,4-D is considered a weak PP for the liver, it was the most effective at inducing renal lesions, indicating that the toxic potency of various PPs will depend on the target organ. JF - Toxicologic pathology AU - Ozaki, K AU - Mahler, J F AU - Haseman, J K AU - Moomaw, C R AU - Nicolette, M L AU - Nyska, A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2001 SP - 440 EP - 450 VL - 29 IS - 4 SN - 0192-6233, 0192-6233 KW - Peroxisome Proliferators KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Pyrimidines KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - pirinixic acid KW - 86C4MRT55A KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Catalase KW - EC 1.11.1.6 KW - Cytochrome P-450 CYP4A KW - EC 1.14.15.3 KW - Index Medicus KW - Animals KW - Proliferating Cell Nuclear Antigen -- analysis KW - Rats KW - Mixed Function Oxygenases -- immunology KW - Mitochondria -- drug effects KW - Catalase -- immunology KW - Mixed Function Oxygenases -- analysis KW - Time Factors KW - Kidney Medulla -- pathology KW - Male KW - Organ Size -- drug effects KW - Administration, Oral KW - Dose-Response Relationship, Drug KW - Kidney Medulla -- ultrastructure KW - Kidney Medulla -- drug effects KW - Mice KW - Catalase -- analysis KW - Cytochrome P-450 Enzyme System -- analysis KW - Mice, Inbred Strains KW - Rats, Sprague-Dawley KW - Microvilli -- drug effects KW - Microvilli -- ultrastructure KW - Mitochondria -- ultrastructure KW - Body Weight -- drug effects KW - Cytochrome P-450 Enzyme System -- immunology KW - Species Specificity KW - Immunohistochemistry KW - Cricetinae KW - Kidney Diseases -- pathology KW - Kidney Tubules -- pathology KW - 2,4-Dichlorophenoxyacetic Acid -- pharmacology KW - Pyrimidines -- pharmacology KW - Peroxisome Proliferators -- pharmacology KW - Kidney Diseases -- enzymology KW - Pyrimidines -- administration & dosage KW - Kidney Tubules -- enzymology KW - Peroxisome Proliferators -- administration & dosage KW - Kidney Tubules -- drug effects KW - Pyrimidines -- toxicity KW - 2,4-Dichlorophenoxyacetic Acid -- administration & dosage KW - Peroxisome Proliferators -- toxicity KW - 2,4-Dichlorophenoxyacetic Acid -- toxicity KW - Kidney Tubules -- ultrastructure KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71175663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Unique+renal+tubule+changes+induced+in+rats+and+mice+by+the+peroxisome+proliferators+2%2C4-dichlorophenoxyacetic+acid+%282%2C4-D%29+and+WY-14643.&rft.au=Ozaki%2C+K%3BMahler%2C+J+F%3BHaseman%2C+J+K%3BMoomaw%2C+C+R%3BNicolette%2C+M+L%3BNyska%2C+A&rft.aulast=Ozaki&rft.aufirst=K&rft.date=2001-07-01&rft.volume=29&rft.issue=4&rft.spage=440&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-29 N1 - Date created - 2001-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A retrospective analysis of background lesions and tissue accountability for male accessory sex organs in Fischer-344 rats. AN - 71175639; 11560252 AB - Because the paired lobes (ventral, dorsal, lateral, and anterior) of the rat prostate have not been consistently sampled in many carcinogenicity and toxicity studies, comparison among different investigations has been compromised. The lack of specific site identification for prostatic lesions further lessens the value of incidences reported. We present here the lobe-specific incidences and degree of severity of background prostatic, seminal vesicular, and ampullary glandular lesions in 1768 control Fischer-344 rats from 35 recent National Toxicology Program 2-year carcinogenicity and toxicity studies conducted in 4 laboratories. The dorsal and lateral lobes were combined and considered the dorsolateral lobe where inflammation, epithelial degeneration, mucinous cysts, and edema were observed. Inflammation in the dorsolateral lobes was significantly associated with pituitary gland adenoma whose prolactin was suggested to play an important role in pathogenesis of prostatic inflammation. Epithelial degeneration, epithelial hyperplasia, inflammation, edema, and adenoma were conspicuous in the ventral lobes. Inflammation and edema occurred in the anterior lobes (coagulating glands). Inflammation, dilatation, epithelial hyperplasia, edema, and adenoma were observed in the seminal vesicles. Inflammation was also present in the ampullary glands. We suggest an optimal embedment and trimming method in rat prostate and seminal vesicle to ensure adequate, consistent sampling. JF - Toxicologic pathology AU - Suwa, T AU - Nyska, A AU - Peckham, J C AU - Hailey, J R AU - Mahler, J F AU - Haseman, J K AU - Maronpot, R R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2001 SP - 467 EP - 478 VL - 29 IS - 4 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Toxicity Tests KW - Retrospective Studies KW - Carcinogenicity Tests KW - Prostatic Hyperplasia -- pathology KW - Time Factors KW - Male KW - Prostatitis -- pathology KW - Prostate -- anatomy & histology KW - Prostatic Diseases -- pathology KW - Prostate -- pathology KW - Seminal Vesicles -- anatomy & histology KW - Histocytological Preparation Techniques -- methods KW - Seminal Vesicles -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71175639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=A+retrospective+analysis+of+background+lesions+and+tissue+accountability+for+male+accessory+sex+organs+in+Fischer-344+rats.&rft.au=Suwa%2C+T%3BNyska%2C+A%3BPeckham%2C+J+C%3BHailey%2C+J+R%3BMahler%2C+J+F%3BHaseman%2C+J+K%3BMaronpot%2C+R+R&rft.aulast=Suwa&rft.aufirst=T&rft.date=2001-07-01&rft.volume=29&rft.issue=4&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-29 N1 - Date created - 2001-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High frequency of ras mutations in forestomach and lung tumors of B6C3F1 mice exposed to 1-amino-2,4-dibromoanthraquinone for 2 years. AN - 71175609; 11560247 AB - 1-Amino-2,4-dibromoanthraquinone (ADBAQ) is an anthraquinone-derived vat dye, and a potent carcinogen in laboratory animals. In a 2-year study with dietary exposure to 10,000 or 20,000 ppm ADBAQ, increased incidence of forestomach and lung tumors were observed in B6C3F1 mice. The present study indentified genetic alterations in H-ras and K-ras proto-oncogenes in ADBAQ-induced tumors. Point mutations in ras proto-oncogenes were identified by restriction fragment length polymorphism, single-stranded conformational polymorphism analysis and cycle sequencing of polymerase chain reaction-amplified DNA isolated from paraffin-embedded squamous cell papillomas and carcinomas in the forestomach, and alveolar/bronchiolar adenomas and carcinomas in the lung. A higher frequency of ras mutations was identified in ADBAQ-induced forestomach (23/32, 72%) and lung tumors (16/23, 70%) than in spontaneous forestomach (4/11, 36%) and lung tumors (26/86, 30%). H-ras codon 61 CTA mutations were detected in (4/8, 50%) ADBAQ-induced forestomach squamous cell papillomas and (10/24, 42%) squamous cell carcinomas, but not in the spontaneous forestomach tumors examined. H-ras codon 61 CGA mutation (6/24, 25%) was also detected in ADBAQ-induced forestomach squamous cell carcinomas. K-ras codon 61 A to T transversions and A to G transitions were prominent in ADBAQ-induced lung alveolar/bronchiolar adenomas and alveolar/bronchiolar carcinomas. The major finding of A to T transversions or A to G transitions in forestomach and lung tumors suggests that ADBAQ or its metabolites target adenine bases in the ras proto-oncogenes and that these mutations play a dominant role in multi-organ JF - Toxicologic pathology AU - Hayashi, S AU - Hong, H H AU - Toyoda, K AU - Ton, T V AU - Devereux, T R AU - Maronpot, R R AU - Huff, J AU - Sills, R C AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. PY - 2001 SP - 422 EP - 429 VL - 29 IS - 4 SN - 0192-6233, 0192-6233 KW - Anthraquinones KW - 0 KW - Carcinogens KW - Codon KW - 1-amino-2,4-dibromoanthraquinone KW - RF75O3IKOZ KW - Index Medicus KW - Animals KW - Gene Frequency KW - Carcinoma, Squamous Cell -- chemically induced KW - Carcinoma, Squamous Cell -- pathology KW - Adenoma -- chemically induced KW - Carcinoma, Squamous Cell -- genetics KW - Point Mutation KW - Adenoma -- pathology KW - Time Factors KW - Papilloma -- chemically induced KW - Male KW - Carcinoma -- genetics KW - Carcinoma -- chemically induced KW - Administration, Oral KW - Exons KW - Mice KW - Papilloma -- genetics KW - Adenocarcinoma, Bronchiolo-Alveolar -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Mice, Inbred Strains KW - Carcinoma -- pathology KW - Adenocarcinoma, Bronchiolo-Alveolar -- chemically induced KW - Polymorphism, Restriction Fragment Length KW - Adenocarcinoma, Bronchiolo-Alveolar -- pathology KW - Adenoma -- genetics KW - Female KW - Stomach Neoplasms -- pathology KW - Stomach Neoplasms -- chemically induced KW - Genes, ras -- drug effects KW - Stomach Neoplasms -- genetics KW - Anthraquinones -- administration & dosage KW - Carcinogens -- toxicity KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Anthraquinones -- toxicity KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71175609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=High+frequency+of+ras+mutations+in+forestomach+and+lung+tumors+of+B6C3F1+mice+exposed+to+1-amino-2%2C4-dibromoanthraquinone+for+2+years.&rft.au=Hayashi%2C+S%3BHong%2C+H+H%3BToyoda%2C+K%3BTon%2C+T+V%3BDevereux%2C+T+R%3BMaronpot%2C+R+R%3BHuff%2C+J%3BSills%2C+R+C&rft.aulast=Hayashi&rft.aufirst=S&rft.date=2001-07-01&rft.volume=29&rft.issue=4&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-29 N1 - Date created - 2001-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor beta, pleiotropic regulator of hematopoietic stem cells: potential physiological and clinical relevance. AN - 71146562; 11530800 AB - Transforming growth factor beta (TGF-beta) is a pleiotropic regulator of all stages of hematopoieis. Depending on the differentiation stage of the target cell, the local environment, and the concentration of TGF-beta, TGF-beta can be proproliferative or antiproliferative, proapoptotic or antiapoptotic, and/or prodifferentiative or antidifferentiative. TGF-beta is the major regulator of stem cell quiescence and can act directly or indirectly through effects on the marrow microenvironment. In addition, paracrine and autocrine actions of TGF-beta have overlapping but distinct regulatory effects on hematopoietic stem/progenitor cells. Neutralization of autocrine TGF-beta has therapeutic potential. JF - International journal of hematology AU - Ruscetti, F W AU - Bartelmez, S H AD - The Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Maryland 21702-1201, USA. ruscettif@ncifcrf.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 18 EP - 25 VL - 74 IS - 1 SN - 0925-5710, 0925-5710 KW - Hematopoietic Cell Growth Factors KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Index Medicus KW - Fetal Blood -- cytology KW - Hematopoiesis -- physiology KW - Animals KW - Receptors, Transforming Growth Factor beta -- physiology KW - Humans KW - Cell Division -- drug effects KW - Autocrine Communication KW - Mice KW - Cells, Cultured -- drug effects KW - Hematopoietic Cell Growth Factors -- pharmacology KW - Transplantation, Homologous KW - Models, Biological KW - Mice, Knockout KW - Receptors, Transforming Growth Factor beta -- drug effects KW - Transfection KW - Hematopoiesis -- drug effects KW - Hematopoietic Stem Cell Transplantation KW - Genetic Vectors -- genetics KW - Retroviridae -- genetics KW - Drug Synergism KW - Transforming Growth Factor beta -- pharmacology KW - Transforming Growth Factor beta -- physiology KW - Hematopoietic Stem Cells -- cytology KW - Transforming Growth Factor beta -- genetics KW - Hematopoietic Stem Cells -- metabolism KW - Transforming Growth Factor beta -- deficiency KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71146562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+hematology&rft.atitle=Transforming+growth+factor+beta%2C+pleiotropic+regulator+of+hematopoietic+stem+cells%3A+potential+physiological+and+clinical+relevance.&rft.au=Ruscetti%2C+F+W%3BBartelmez%2C+S+H&rft.aulast=Ruscetti&rft.aufirst=F&rft.date=2001-07-01&rft.volume=74&rft.issue=1&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=International+journal+of+hematology&rft.issn=09255710&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Int J Hematol. 2001 Jul;74(1):1-2 [11530797] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repetitious appearance and disappearance of different kinds of clonal cytogenetic abnormalities after allogeneic bone marrow transplantation. AN - 71141970; 11530811 AB - We report a childhood case that showed the repeated appearance and disappearance of various kinds of cytogenetic abnormalities (CA) for 5.5 years after allogeneic bone marrow transplantation (BMT). The patient underwent allogeneic BMT from an HLA-matched unrelated donor during the second complete remission of acute lymphoblastic leukemia. The conditioning regimen for BMT consisted of etoposide, cyclophosphamide, anti-human thymocyte immunoglobulin, and total body irradiation. There were no leukemic relapses or secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) since the BMT. The CA occurred from residual recipient cells, which were damaged by chemotherapy or radiation prior to BMT. Although previous studies about post-BMT CA had reported the continuous emergence of identical clones, the present case showed the appearance of one different type of clone after another. Although the appearance of different types of CA may mean that these clones did not obtain any growth advantages, it may be a sign of genomic instability, which is probably a risk factor for the development of secondary AML/MDS. JF - International journal of hematology AU - Lin, Y W AU - Hamahata, K AU - Watanabe, K AU - Adachi, S AU - Akiyama, Y AU - Kubota, M AU - Nakahata, T AD - Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan. linying@mail.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 86 EP - 89 VL - 74 IS - 1 SN - 0925-5710, 0925-5710 KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisolone KW - 9PHQ9Y1OLM KW - 6-Mercaptopurine KW - E7WED276I5 KW - Asparaginase KW - EC 3.5.1.1 KW - Methylprednisolone KW - X4W7ZR7023 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Karyotyping KW - Cyclophosphamide -- administration & dosage KW - Daunorubicin -- administration & dosage KW - Methylprednisolone -- administration & dosage KW - Combined Modality Therapy KW - DNA Damage KW - Humans KW - Vincristine -- administration & dosage KW - In Situ Hybridization, Fluorescence KW - Asparaginase -- administration & dosage KW - Transplantation, Homologous KW - Cytarabine -- administration & dosage KW - Child, Preschool KW - Follow-Up Studies KW - 6-Mercaptopurine -- administration & dosage KW - Prednisolone -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Time Factors KW - Methotrexate -- administration & dosage KW - Female KW - Remission Induction KW - Clone Cells -- radiation effects KW - Transplantation Conditioning KW - Chromosome Disorders KW - Chromosome Aberrations KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- therapy KW - Clone Cells -- ultrastructure KW - Bone Marrow Transplantation KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- genetics KW - Clone Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71141970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+hematology&rft.atitle=Repetitious+appearance+and+disappearance+of+different+kinds+of+clonal+cytogenetic+abnormalities+after+allogeneic+bone+marrow+transplantation.&rft.au=Lin%2C+Y+W%3BHamahata%2C+K%3BWatanabe%2C+K%3BAdachi%2C+S%3BAkiyama%2C+Y%3BKubota%2C+M%3BNakahata%2C+T&rft.aulast=Lin&rft.aufirst=Y&rft.date=2001-07-01&rft.volume=74&rft.issue=1&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=International+journal+of+hematology&rft.issn=09255710&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Understanding and treating drug abuse and addiction. AN - 71056817; 11484635 JF - Business and health AU - Leshner, A I AD - National Institutes of Health, Bethesda, Md., USA. PY - 2001 SP - 23 EP - 30 VL - 19 IS - 7 SN - 0739-9413, 0739-9413 KW - Psychotropic Drugs KW - 0 KW - Health administration KW - United States KW - Brain -- physiopathology KW - Drug and Narcotic Control KW - Motivation KW - Humans KW - Substance-Related Disorders -- physiopathology KW - Occupational Health KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71056817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Business+and+health&rft.atitle=Understanding+and+treating+drug+abuse+and+addiction.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=2001-07-01&rft.volume=19&rft.issue=7&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Business+and+health&rft.issn=07399413&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro T-cell receptor V beta repertoire analysis may identify which T-cell V beta families mediate graft-versus-leukaemia and graft-versus-host responses after human leucocyte antigen-matched sibling stem cell transplantation. AN - 71038747; 11472345 AB - We studied oligoclonal T-cell expansions of 24 T-cell receptor (TCR) V beta families in normal donor lymphocytes stimulated with patient's cells and in recipient blood after transplant, using a polymerase chain reaction-based assay (spectratyping). T cells from donor blood were incubated with separated myeloid leukaemia cells or T cells from the HLA-identical sibling recipient. In five of the six patients tested, the T-cell V beta skewing pattern observed in vitro was seen in vivo after transplant. After transplant, the myeloid-specific V beta skewing coincided with the disappearance of residual disease in three patients and in one patient skewing was lost at the time of leukaemic relapse. In functional tests, T cells generated against leukaemic cells in vitro produced interferon gamma in response to the leukaemia. Removal of the leukaemia-expanded skewed V beta families significantly decreased cytotoxic killing of the leukaemia. However, while there was a general concordance in the V beta family exhibiting clonal expansion in vitro and in vivo, the exact clonotype expanded in vitro and in vivo differed. These findings suggest that alloresponses involve multiple T-cell clones within a restricted TCR V beta repertoire that undergo different selection pressures in vitro and in vivo. JF - British journal of haematology AU - Epperson, D E AU - Margolis, D A AU - McOlash, L AU - Janczak, T AU - Barrett, A J AD - Bone Marrow Transplant Unit, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 57 EP - 62 VL - 114 IS - 1 SN - 0007-1048, 0007-1048 KW - Receptors, Antigen, T-Cell, alpha-beta KW - 0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Acute Disease KW - Polymerase Chain Reaction KW - Coculture Techniques KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- immunology KW - Histocompatibility Testing KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Interferon-gamma -- immunology KW - Transplantation, Homologous KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- therapy KW - Graft vs Leukemia Effect -- immunology KW - T-Lymphocytes -- metabolism KW - Graft vs Host Disease -- immunology KW - Leukemia, Myeloid -- immunology KW - Hematopoietic Stem Cell Transplantation KW - Leukemia, Myeloid -- therapy KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71038747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+haematology&rft.atitle=In+vitro+T-cell+receptor+V+beta+repertoire+analysis+may+identify+which+T-cell+V+beta+families+mediate+graft-versus-leukaemia+and+graft-versus-host+responses+after+human+leucocyte+antigen-matched+sibling+stem+cell+transplantation.&rft.au=Epperson%2C+D+E%3BMargolis%2C+D+A%3BMcOlash%2C+L%3BJanczak%2C+T%3BBarrett%2C+A+J&rft.aulast=Epperson&rft.aufirst=D&rft.date=2001-07-01&rft.volume=114&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=British+journal+of+haematology&rft.issn=00071048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases. AN - 71026807; 11461973 AB - Oxidative stress generated by dopamine (DA) oxidation could be one of the factors underlying the selective vulnerability of nigral dopaminergic neurons in Parkinson's diseases. Here we show that DA induces apoptosis in SH-SY5Y neuroblastoma cells demonstrated by activation of caspase-9 and caspase-3, cleavage of poly(ADP-ribose) polymerase as well as nuclear condensation. We also show that p38 mitogen-activated protein kinase is activated within 10 min of DA treatment, which precedes the onset of apoptosis because the potent p38 kinase inhibitor SB203580 protects against DA-induced cell death as well as against caspase-9 and caspase-3 activation. In addition, the antioxidant N-acetyl-L-cysteine (NAC) effectively blocks DA-induced p38 kinase activation, caspase-9 and caspase-3 cleavage and subsequent apoptosis, indicating that DA triggers apoptosis via a signaling pathway that is initiated by the generation of reactive oxygen species (ROS). Dopamine exerts its toxicity principally intracellularly as the DA uptake inhibitor, nomifensine significantly reduces DA-induced cell death as well as activation of p38 kinase and caspase-3. Furthermore, DA induces mitochondrial cytochrome c release, which is dependent on p38 kinase activation and precedes the cleavage of caspases. These observations indicate that DA induces apoptosis primarily by generating ROS, p38 kinase activation, cytochrome c release followed by caspase-9 and caspase-3 activation. JF - Journal of neurochemistry AU - Junn, E AU - Mouradian, M M AD - Genetic Pharmacology Unit, Experimental Therapeutics Branch, NINDS, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 374 EP - 383 VL - 78 IS - 2 SN - 0022-3042, 0022-3042 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Cysteine Proteinase Inhibitors KW - Cytochrome c Group KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Nomifensine KW - 1LGS5JRP31 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP9 protein, human KW - Caspase 3 KW - Caspase 9 KW - Caspases KW - Dopamine KW - VTD58H1Z2X KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Cell Death -- physiology KW - Humans KW - Biological Transport KW - Acetylcysteine -- pharmacology KW - Cell Death -- drug effects KW - Neuroblastoma KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Signal Transduction -- physiology KW - Tumor Cells, Cultured KW - Kinetics KW - Signal Transduction -- drug effects KW - Nomifensine -- pharmacology KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Oxidative Stress -- physiology KW - Dopamine -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Dopamine -- metabolism KW - Cytochrome c Group -- metabolism KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71026807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Apoptotic+signaling+in+dopamine-induced+cell+death%3A+the+role+of+oxidative+stress%2C+p38+mitogen-activated+protein+kinase%2C+cytochrome+c+and+caspases.&rft.au=Junn%2C+E%3BMouradian%2C+M+M&rft.aulast=Junn&rft.aufirst=E&rft.date=2001-07-01&rft.volume=78&rft.issue=2&rft.spage=374&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil. AN - 71022514; 11459999 AB - 5-Fluorouracil (5-FU)-associated neurotoxicity is uncommon; symptoms may occur abruptly or more gradually during the course of chemotherapy. Peripheral neuropathy with 5-FU therapy has only rarely been reported. Two patients treated in a phase I trial of oral 5-FU, leucovorin and eniluracil, an inhibitor of dihydropyrimidine dehydrogenase (DPD), developed delayed onset symptoms of unsteady gait and reduced sensation in the legs. Magnetic resonance imaging scans of the brain and neurologic examination did not support a CNS basis for the condition. Electromyograms and nerve conduction studies revealed sensorimotor polyneuropathy. Other common etiologies of peripheral neuropathy were excluded. The neurological condition of these patients stabilized after 5-FU dose reduction and partial resolution gradually occurred when protocol therapy was stopped. Although CNS symptoms may rarely complicate 5-FU therapy, peripheral neuropathy is unexpected. Patients with DPD deficiency treated with conventional doses of 5-FU typically develop acute CNS toxicity shortly after therapy, accompanied by extremely high systemic exposure to 5-FU. Patients with normal 5-FU clearance may also experience CNS toxicity, particularly with high-dose schedules, and both parent drug and its catabolites may be contributory. Since DPD was profoundly inhibited during eniluracil therapy in these two patients, it is likely that 5-FU or its active metabolites were contributing factors to the peripheral neuropathy. JF - Anti-cancer drugs AU - Saif, M W AU - Wilson, R H AU - Harold, N AU - Keith, B AU - Dougherty, D S AU - Grem, J L AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 525 EP - 531 VL - 12 IS - 6 SN - 0959-4973, 0959-4973 KW - eniluracil KW - 2E2W0W5XIU KW - Uracil KW - 56HH86ZVCT KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Magnetic Resonance Imaging KW - Oxidoreductases -- blood KW - Humans KW - Brain -- pathology KW - Colonic Neoplasms -- drug therapy KW - Adult KW - Electromyography KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Fluorouracil -- administration & dosage KW - Uracil -- analogs & derivatives KW - Uracil -- administration & dosage KW - Peripheral Nervous System Diseases -- etiology KW - Leucovorin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71022514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Peripheral+neuropathy+associated+with+weekly+oral+5-fluorouracil%2C+leucovorin+and+eniluracil.&rft.au=Saif%2C+M+W%3BWilson%2C+R+H%3BHarold%2C+N%3BKeith%2C+B%3BDougherty%2C+D+S%3BGrem%2C+J+L&rft.aulast=Saif&rft.aufirst=M&rft.date=2001-07-01&rft.volume=12&rft.issue=6&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients. AN - 71014586; 11443628 AB - The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used. Copyright 2001 American Cancer Society. JF - Cancer AU - Spina, M AU - Vaccher, E AU - Juzbasic, S AU - Milan, I AU - Nasti, G AU - Talamini, R AU - Fasan, M AU - Antinori, A AU - Nigra, E AU - Tirelli, U AD - Division of Medical Oncology A, National Cancer Institute, Aviano (PN), Italy. Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 200 EP - 206 VL - 92 IS - 1 SN - 0008-543X, 0008-543X KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Disease-Free Survival KW - Doxorubicin -- adverse effects KW - Infusions, Intravenous KW - Humans KW - Aged KW - Doxorubicin -- administration & dosage KW - Cyclophosphamide -- adverse effects KW - Etoposide -- administration & dosage KW - Adult KW - Treatment Outcome KW - Etoposide -- adverse effects KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- mortality KW - Lymphoma, AIDS-Related -- mortality KW - Lymphoma, AIDS-Related -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71014586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Human+immunodeficiency+virus-related+non-Hodgkin+lymphoma%3A+activity+of+infusional+cyclophosphamide%2C+doxorubicin%2C+and+etoposide+as+second-line+chemotherapy+in+40+patients.&rft.au=Spina%2C+M%3BVaccher%2C+E%3BJuzbasic%2C+S%3BMilan%2C+I%3BNasti%2C+G%3BTalamini%2C+R%3BFasan%2C+M%3BAntinori%2C+A%3BNigra%2C+E%3BTirelli%2C+U&rft.aulast=Spina&rft.aufirst=M&rft.date=2001-07-01&rft.volume=92&rft.issue=1&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is Smad3 a major player in signal transduction pathways leading to fibrogenesis? AN - 71014074; 11451911 AB - Transforming growth factor (TGF)-beta plays a central role in fibrosis, contributing both to the influx and activation of inflammatory cells, as well as to activation of fibroblasts to elaborate extracellular matrix. In the past few years, new insight has been gained into signal transduction pathways downstream of the TGF-beta receptor serine-threonine kinases with the identification of a family of evolutionarily conserved Smad proteins. Two receptor-activated Smad proteins, Smad2 and Smad3, are phosphorylated by the activated TGF-beta type I receptor kinase, after which they partner with the common mediator, Smad4, and are translocated to the nucleus to where they participate in transcriptional complexes to control expression of target genes. We have shown in wound healing studies of mice null for Smad3, that loss of this key signaling intermediate interferes with the chemotaxis of inflammatory cells to TGF-beta as well as with their ability to autoinduce TGF-beta. Moreover, studies with mouse embryo fibroblasts null for Smad3 show that TGF-beta-dependent induction of c-Jun and c-Fos, important in induction of collagen as well as in autoinduction of TGF-beta, is mediated by Smad3. Based on these observations, we hypothesize that loss of Smad3 will confer resistance to fibrosis and result in reduced inflammatory cell infiltrates, reduced autoinduction of TGF-beta, important to sustain the process, and reduced elaboration of collagen. Preliminary observations in a model of radiation-induced fibrosis confirm this hypothesis and suggest that inhibitors of Smad3 might have clinical application both to improve wound healing and to reduce fibrosis. JF - Chest AU - Roberts, A B AU - Piek, E AU - Böttinger, E P AU - Ashcroft, G AU - Mitchell, J B AU - Flanders, K C AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Robertsa@dce41.nci.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 43S EP - 47S VL - 120 IS - 1 Suppl SN - 0012-3692, 0012-3692 KW - DNA-Binding Proteins KW - 0 KW - SMAD3 protein, human KW - Smad3 Protein KW - Trans-Activators KW - Transforming Growth Factor beta KW - Abridged Index Medicus KW - Index Medicus KW - MAP Kinase Signaling System -- physiology KW - Phosphorylation KW - Humans KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology KW - Pulmonary Fibrosis -- physiopathology KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Wound Healing -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71014074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest&rft.atitle=Is+Smad3+a+major+player+in+signal+transduction+pathways+leading+to+fibrogenesis%3F&rft.au=Roberts%2C+A+B%3BPiek%2C+E%3BB%C3%B6ttinger%2C+E+P%3BAshcroft%2C+G%3BMitchell%2C+J+B%3BFlanders%2C+K+C&rft.aulast=Roberts&rft.aufirst=A&rft.date=2001-07-01&rft.volume=120&rft.issue=1+Suppl&rft.spage=43S&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Resisting resistance. AN - 71005217; 11446354 JF - Trends in parasitology AU - Sina, B J AU - Aultman, K Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 305 EP - 306 VL - 17 IS - 7 KW - Insecticides KW - 0 KW - Index Medicus KW - Animals KW - Insecticide Resistance KW - Africa KW - Research KW - Anopheles -- drug effects KW - Malaria -- transmission KW - Insect Vectors -- drug effects KW - Mosquito Control KW - Insecticides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71005217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Trends+in+parasitology&rft.atitle=Resisting+resistance.&rft.au=Sina%2C+B+J%3BAultman%2C+K&rft.aulast=Sina&rft.aufirst=B&rft.date=2001-07-01&rft.volume=17&rft.issue=7&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Trends+in+parasitology&rft.issn=14714922&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Roles of Akt/PKB and IKK complex in constitutive induction of NF-kappaB in hepatocellular carcinomas of transforming growth factor alpha/c-myc transgenic mice. AN - 71004522; 11431731 AB - NF-kappaB regulates liver cell death during development, regeneration, and neoplastic transformation. For example, we showed that oncogenic Ras- or Raf-mediated transformation of rat liver epithelial cells (RLEs) led to altered NF-kappaB regulation through IKK complex activation, which rendered these cells more resistant to TGF-beta1-induced apoptosis. Thus, based on these findings, we sought to determine whether NF-kappaB could also be involved in tumor growth of liver cells in vivo. Hepatocellular carcinomas (HCCs) derived from bitransgenic mice harboring TGF-alpha and c-myc transgenes targeted specifically to the liver were compared with HCCs from c-myc single transgenic mice. Tumors from bitransgenic mice are characterized by a higher frequency of appearance, lower apoptotic index, and a higher rate of cell proliferation. Here we show that NF-kappaB is activated in HCCs of double TGF-alpha/c-myc transgenic mice, but not of c-myc single transgenic mice, suggesting that TGF-alpha mediates induction of NF-kappaB. Activation of the IKK complex was observed in the HCCs of double TGF-alpha/c-myc transgenic mice, implicating this pathway in NF-kappaB induction. Lastly, activation of the Akt/protein kinase B (PKB), which has recently been implicated in NF-kappaB activation by PDGF, TNF-alpha, and Ras, was also observed. Importantly, human HCC cell lines similarly displayed NF-kappaB activation. Thus, these studies elucidate an anti-apoptotic mechanism by a TGF-alpha-Akt/PKB-IKK pathway, which likely contributes to survival and proliferation, thereby accelerating c-myc-induced liver neoplastic development in vivo. JF - Hepatology (Baltimore, Md.) AU - Factor, V AU - Oliver, A L AU - Panta, G R AU - Thorgeirsson, S S AU - Sonenshein, G E AU - Arsura, M AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 32 EP - 41 VL - 34 IS - 1 SN - 0270-9139, 0270-9139 KW - Carrier Proteins KW - 0 KW - Ikbkap protein, mouse KW - Ikbkap protein, rat KW - NF-kappa B KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myc KW - Transforming Growth Factor alpha KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Animals KW - Apoptosis KW - Enzyme Activation KW - Gene Expression KW - Liver -- metabolism KW - Mice KW - Mice, Transgenic KW - Male KW - Cell Division KW - NF-kappa B -- biosynthesis KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- metabolism KW - Transforming Growth Factor alpha -- physiology KW - Proto-Oncogene Proteins c-myc -- physiology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Carrier Proteins -- physiology KW - Proto-Oncogene Proteins -- physiology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71004522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Roles+of+Akt%2FPKB+and+IKK+complex+in+constitutive+induction+of+NF-kappaB+in+hepatocellular+carcinomas+of+transforming+growth+factor+alpha%2Fc-myc+transgenic+mice.&rft.au=Factor%2C+V%3BOliver%2C+A+L%3BPanta%2C+G+R%3BThorgeirsson%2C+S+S%3BSonenshein%2C+G+E%3BArsura%2C+M&rft.aulast=Factor&rft.aufirst=V&rft.date=2001-07-01&rft.volume=34&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Root and spinal cord compression from methylmethacrylate vertebroplasty. AN - 71003972; 11458170 AB - Case report and literature review. Clinicians use methylmethacrylate vertebroplasty to treat vertebral hemangiomas, metastases, and osteoporotic fractures. Cement may leak out of the vertebral body and compress the adjacent spinal cord and nerve roots. We review a case of nerve-root and cord compression from methylmethacrylate extrusion during vertebroplasty. A 50-year-old female presented with disabling thoracic back pain. A metastasis to T1 was discovered, with collapse of the vertebral body but without cord compression. Methylmethacrylate vertebroplasty was performed. After injection, portable computed tomography (CT) showed a leakage of methylmethacrylate into the C8 and T1 foramina and spinal canal. Radiculopathy and myelopathy developed. Surgical decompression using the anterior approach was necessary. Case report. Early surgical intervention decompressed the neural elements and relieved the neurological deficits. Neurologic complications of methylmethacrylate vertebroplasty necessitate active involvement of spine surgeons in patient evaluation and management. JF - Spine AU - Ratliff, J AU - Nguyen, T AU - Heiss, J AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20892, USA. jratliff@box-j.nih.gov Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - E300 EP - E302 VL - 26 IS - 13 SN - 0362-2436, 0362-2436 KW - Bone Cements KW - 0 KW - Vasodilator Agents KW - Methylmethacrylate KW - 196OC77688 KW - Index Medicus KW - Orthopedic Procedures KW - Humans KW - Middle Aged KW - Back Pain -- surgery KW - Spinal Cord Diseases -- etiology KW - Radiculopathy -- etiology KW - Female KW - Vasodilator Agents -- adverse effects KW - Spinal Cord Compression -- etiology KW - Spinal Neoplasms -- surgery KW - Thoracic Vertebrae -- surgery KW - Prostheses and Implants -- adverse effects KW - Methylmethacrylate -- adverse effects KW - Bone Cements -- adverse effects KW - Thoracic Vertebrae -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71003972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Spine&rft.atitle=Root+and+spinal+cord+compression+from+methylmethacrylate+vertebroplasty.&rft.au=Ratliff%2C+J%3BNguyen%2C+T%3BHeiss%2C+J&rft.aulast=Ratliff&rft.aufirst=J&rft.date=2001-07-01&rft.volume=26&rft.issue=13&rft.spage=E300&rft.isbn=&rft.btitle=&rft.title=Spine&rft.issn=03622436&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. AN - 70997585; 11448901 AB - Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize. Based on those data, we initiated a Phase II trial of thalidomide in patients with metastatic androgen-independent prostate cancer. This was an open-label, randomized Phase II study. Thalidomide was administered either at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that escalated to 1200 mg/day (high-dose arm). A total of 63 patients were enrolled onto the study (50 patients on the low-dose arm and 13 patients on the high-dose arm). Serum prostate-specific antigen (PSA) decline of > or = 50% was noted in 18% of patients on the low-dose arm and in none of the patients on the high-dose arm. Four patients were maintained for > 150 days. The most prevalent complications were constipation, fatigue, neurocortical, and neurosensory. Thalidomide, an antiangiogenesis agent, has some activity in patients with metastatic prostate cancer who have failed multiple therapies. A total of 27% of all patients had a decline in PSA of > or = 40%, often associated with an improvement of clinical symptoms. Because our preclinical studies had shown that thalidomide increases PSA secretion, we believe that the magnitude of PSA decline seen in our trial justifies further study. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Figg, W D AU - Dahut, W AU - Duray, P AU - Hamilton, M AU - Tompkins, A AU - Steinberg, S M AU - Jones, E AU - Premkumar, A AU - Linehan, W M AU - Floeter, M K AU - Chen, C C AU - Dixon, S AU - Kohler, D R AU - Krüger, E A AU - Gubish, E AU - Pluda, J M AU - Reed, E AD - Medicine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. wdfigg@helix.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 1888 EP - 1893 VL - 7 IS - 7 SN - 1078-0432, 1078-0432 KW - Androgens KW - 0 KW - Angiogenesis Inhibitors KW - Endothelial Growth Factors KW - Lymphokines KW - Lymphotoxin-alpha KW - Tumor Necrosis Factor-alpha KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Thalidomide KW - 4Z8R6ORS6L KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Lymphokines -- blood KW - Humans KW - Aged KW - Neutropenia -- chemically induced KW - Prostate-Specific Antigen -- drug effects KW - Aged, 80 and over KW - Tumor Necrosis Factor-alpha -- drug effects KW - Lymphotoxin-alpha -- blood KW - Prostate-Specific Antigen -- blood KW - Treatment Outcome KW - Mood Disorders -- chemically induced KW - Time Factors KW - Fibroblast Growth Factor 2 -- drug effects KW - Male KW - Survival Analysis KW - Dose-Response Relationship, Drug KW - Neovascularization, Pathologic -- pathology KW - Lymphokines -- drug effects KW - Androgens -- physiology KW - Fibroblast Growth Factor 2 -- blood KW - Follow-Up Studies KW - Middle Aged KW - Tumor Necrosis Factor-alpha -- metabolism KW - Endothelial Growth Factors -- blood KW - Angiogenesis Inhibitors -- therapeutic use KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- blood supply KW - Thalidomide -- therapeutic use KW - Prostatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70997585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+randomized+phase+II+trial+of+thalidomide%2C+an+angiogenesis+inhibitor%2C+in+patients+with+androgen-independent+prostate+cancer.&rft.au=Figg%2C+W+D%3BDahut%2C+W%3BDuray%2C+P%3BHamilton%2C+M%3BTompkins%2C+A%3BSteinberg%2C+S+M%3BJones%2C+E%3BPremkumar%2C+A%3BLinehan%2C+W+M%3BFloeter%2C+M+K%3BChen%2C+C+C%3BDixon%2C+S%3BKohler%2C+D+R%3BKr%C3%BCger%2C+E+A%3BGubish%2C+E%3BPluda%2C+J+M%3BReed%2C+E&rft.aulast=Figg&rft.aufirst=W&rft.date=2001-07-01&rft.volume=7&rft.issue=7&rft.spage=1888&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity related to oxidative and nitrosative stress by nitric oxide. AN - 70997581; 11444095 JF - Experimental biology and medicine (Maywood, N.J.) AU - Wink, D A AU - Miranda, K M AU - Espey, M G AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 621 EP - 623 VL - 226 IS - 7 SN - 1535-3702, 1535-3702 KW - Oxidants KW - 0 KW - Reactive Oxygen Species KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Oxidants -- pharmacology KW - Oxidative Stress KW - Nitric Oxide -- pharmacology KW - Cell Death -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70997581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.atitle=Cytotoxicity+related+to+oxidative+and+nitrosative+stress+by+nitric+oxide.&rft.au=Wink%2C+D+A%3BMiranda%2C+K+M%3BEspey%2C+M+G&rft.aulast=Wink&rft.aufirst=D&rft.date=2001-07-01&rft.volume=226&rft.issue=7&rft.spage=621&rft.isbn=&rft.btitle=&rft.title=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.issn=15353702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression of ionic channels in rat anterior pituitary cells. AN - 70985289; 11435620 AB - Secretory anterior pituitary cells are of the same origin, but exhibit cell type-specific patterns of spontaneous intracellular Ca2+ signaling and basal hormone secretion. To understand the underlying ionic mechanisms mediating these differences, we compared the ionic channels expressed in somatotrophs, lactotrophs, and gonadotrophs from randomly cycling female rats under identical cell culture and recording conditions. Our results indicate that a similar group of ionic channels are expressed in each cell type, including transient and sustained voltage-gated Ca2+ channels, tetrodotoxin-sensitive Na+ channels, transient and delayed rectifying K+ channels, and multiple Ca2+ -sensitive K+ channel subtypes. However, there were marked differences in the expression levels of some of the ionic channels. Specifically, lactotrophs and somatotrophs exhibited low expression levels of tetrodotoxin-sensitive Na+ channels and high expression levels of the large-conductance, Ca2+ -activated K+ channel compared with those observed in gonadotrophs. In addition, functional expression of the transient K+ channel was much higher in lactotrophs and gonadotrophs than in somatotrophs. Finally, the expression of the transient voltage-gated Ca2+ channels was higher in somatotrophs than in lactotrophs and gonadotrophs. These results indicate that there are cell type-specific patterns of ionic channel expression, which may be of physiological significance for the control of Ca2+ homeostasis and secretion in unstimulated and receptor-stimulated anterior pituitary cells. JF - Molecular endocrinology (Baltimore, Md.) AU - Van Goor, F AU - Zivadinovic, D AU - Stojilkovic, S S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892-4510, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 1222 EP - 1236 VL - 15 IS - 7 SN - 0888-8809, 0888-8809 KW - Calcium Channels KW - 0 KW - Gonadotropins, Pituitary KW - Ion Channels KW - Potassium Channels KW - Sodium Channels KW - Tetrodotoxin KW - 4368-28-9 KW - Prolactin KW - 9002-62-4 KW - Growth Hormone KW - 9002-72-6 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Gonadotropins, Pituitary -- secretion KW - Animals KW - Sodium Channels -- genetics KW - Humans KW - Potassium Channels -- genetics KW - Calcium -- pharmacology KW - Calcium Channels -- genetics KW - Electrophysiology KW - Rats KW - Ion Channel Gating -- physiology KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Prolactin -- secretion KW - Tetrodotoxin -- pharmacology KW - Female KW - Growth Hormone -- secretion KW - Pituitary Gland, Anterior -- metabolism KW - Pituitary Gland, Anterior -- secretion KW - Gene Expression KW - Ion Channels -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70985289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Differential+expression+of+ionic+channels+in+rat+anterior+pituitary+cells.&rft.au=Van+Goor%2C+F%3BZivadinovic%2C+D%3BStojilkovic%2C+S+S&rft.aulast=Van+Goor&rft.aufirst=F&rft.date=2001-07-01&rft.volume=15&rft.issue=7&rft.spage=1222&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular identification and characterization of a and b forms of the glucocorticoid receptor. AN - 70982268; 11435610 AB - The human glucocorticoid receptor (hGRalpha) is a ligand-activated transcription factor that mediates the physiological effects of corticosteroid hormones and is essential for life. Originally cloned in 1986, the transcriptionally active hGRalpha was reported to be a single protein species of 777 amino acids (molecular mass = 94 kDa). Biochemical data, obtained using various mammalian tissues and cell lines, however, have consistently revealed an additional, slightly smaller, second hGR protein (molecular mass = 91 kDa) that is not recognized by antibodies specific for the transcriptionally inactive and dominant negative, non-hormone-binding hGRbeta isoform. We report here that when a single GR cDNA is transfected in COS-1 cells, or transcribed and translated in vitro, two forms of the receptor are observed, similar to those seen in cells that contain endogenous GR. These data suggest that two forms of the hGRalpha are produced by alternative translation of the same gene and are henceforth termed GR-A and GR-B. To test this hypothesis, we have investigated the role of an internal ATG codon corresponding to methionine 27 (M27) as a potential alternative translation initiation site for the GR. Mutagenesis of this ATG codon to ACG in human, rat, and mouse GR cDNA results in generation of a single 94-kDa protein species, GR-A. Moreover, mutagenesis of the initial ATG codon to ACG (Met 1 to Thr) also resulted in production of single, shorter protein species (91 kDa), GR-B. Mutagenesis of the Kozak translation initiation sequence strongly indicates that a leaky ribosomal scanning mechanism is responsible for generating the GR-A and -B isoforms. Western blot analysis using peptide-specific antibodies show both the A and B receptor forms are present in human cell lines. Both receptors exhibit similar subcellular localization and nuclear translocation after ligand activation. Functional analyses of hGR-A and hGR-B under various glucocorticoid-responsive promoters reveal the shorter hGR-B to be nearly twice as effective as the longer hGR-A species in gene transactivation, but not in transrepression. JF - Molecular endocrinology (Baltimore, Md.) AU - Yudt, M R AU - Cidlowski, J A AD - Laboratory of Signal Transduction National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 1093 EP - 1103 VL - 15 IS - 7 SN - 0888-8809, 0888-8809 KW - Codon KW - 0 KW - DNA, Complementary KW - Glucocorticoids KW - Protease Inhibitors KW - Receptors, Glucocorticoid KW - Recombinant Proteins KW - Dexamethasone KW - 7S5I7G3JQL KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Animals KW - Protease Inhibitors -- pharmacology KW - COS Cells KW - Dexamethasone -- pharmacology KW - Humans KW - Gene Expression KW - DNA, Complementary -- analysis KW - Molecular Weight KW - Mutagenesis KW - Rats KW - Phosphorylation KW - Molecular Sequence Data KW - Response Elements KW - Male KW - Protein Biosynthesis KW - DNA, Complementary -- genetics KW - Amino Acid Sequence KW - Mice KW - Transcriptional Activation KW - Glucocorticoids -- pharmacology KW - Blotting, Western KW - Rats, Sprague-Dawley KW - Transfection KW - Alternative Splicing KW - Endopeptidases -- metabolism KW - Species Specificity KW - Cell Line KW - Receptors, Glucocorticoid -- chemistry KW - Receptors, Glucocorticoid -- analysis KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70982268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Molecular+identification+and+characterization+of+a+and+b+forms+of+the+glucocorticoid+receptor.&rft.au=Yudt%2C+M+R%3BCidlowski%2C+J+A&rft.aulast=Yudt&rft.aufirst=M&rft.date=2001-07-01&rft.volume=15&rft.issue=7&rft.spage=1093&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Marijuana Craving Questionnaire: development and initial validation of a self-report instrument. AN - 70980013; 11440613 AB - To develop and validate a multi-dimensional questionnaire on marijuana craving. Current marijuana smokers (n = 217) not seeking treatment completed a 47-item Marijuana Craving Questionnaire (MCQ) and forms assessing demographics, drug use history, marijuana quit attempts and current mood. Exploratory and confirmatory factor analyses indicated that a four-factor solution best described the item structure. Factor subscales derived from the 17 items with significant loadings had respectable internal consistencies and were stable across settings and subgroups. The subscales exhibited low to moderate, positive intercorrelations and were significantly correlated with marijuana use history and a wide range of single-item measures of craving. Findings suggested that four specific constructs characterize craving for marijuana: (1) compulsivity, an inability to control marijuana use; (2) emotionality, use of marijuana in anticipation of relief from withdrawal or negative mood; (3) expectancy, anticipation of positive outcomes from smoking marijuana; and (4) purposefulness, intention and planning to use marijuana for positive outcomes. These data indicate that the MCQ is a valid and reliable instrument for assessing marijuana craving in individuals not seeking drug abuse treatment and that marijuana craving can be measured in the absence of withdrawal. JF - Addiction (Abingdon, England) AU - Heishman, S J AU - Singleton, E G AU - Liguori, A AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA. sheih@intra.nida.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 1023 EP - 1034 VL - 96 IS - 7 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Sensitivity and Specificity KW - Emotions KW - Humans KW - Adult KW - Substance Withdrawal Syndrome -- psychology KW - Male KW - Female KW - Surveys and Questionnaires -- standards KW - Marijuana Abuse -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70980013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Marijuana+Craving+Questionnaire%3A+development+and+initial+validation+of+a+self-report+instrument.&rft.au=Heishman%2C+S+J%3BSingleton%2C+E+G%3BLiguori%2C+A&rft.aulast=Heishman&rft.aufirst=S&rft.date=2001-07-01&rft.volume=96&rft.issue=7&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lowering the isoelectric point of the Fv portion of recombinant immunotoxins leads to decreased nonspecific animal toxicity without affecting antitumor activity. AN - 70978842; 11431343 AB - Recombinant immunotoxins are genetically engineered proteins in which the Fv portion of an antibody is fused to a toxin. Our laboratory uses a 38-kDa form of Pseudomonas exotoxin A termed PE38 for this purpose. Clinical studies with immunotoxins targeting CD25 and CD22 have shown that dose-limiting side effects are attributable to liver damage and other inflammatory toxicities. We recently showed that mutating exposed surface neutral residues to acidic residues in the framework region of the Fv portion of an immunotoxin targeting CD25 [anti-Tac(scFv)-PE38] lowered its isoelectric point (pI) and decreased its toxicity in mice without impairing its cytotoxic or antitumor activities. We have now extended these studies and made mutations that change basic residues to neutral or acidic residues. Initially the pI of the mutant Fv (M1) of anti-Tac(scFv)-PE38 was decreased further. Subsequently, mutations were made in two other immunotoxins, SS1(dsFv)-PE38 targeting ovarian cancer and B3(dsFv)-PE38 targeting colon and breast cancers. We have found that all these mutant molecules fully retained specific target cell cytotoxicity and antitumor activity but were considerably less toxic to mice. Therefore, lowering the pI of the Fv may be a general approach to diminish the nonspecific toxicity of recombinant immunotoxins and other Fv fusion proteins without losing antitumor activity. JF - Cancer research AU - Onda, M AU - Nagata, S AU - Tsutsumi, Y AU - Vincent, J J AU - Wang , Q AU - Kreitman, R J AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 5070 EP - 5077 VL - 61 IS - 13 SN - 0008-5472, 0008-5472 KW - Antibodies KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - antitac(FV)-PE38 recombinant immunotoxin KW - immunoglobulin Fv KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Immunoglobulin Variable Region -- genetics KW - Animals KW - Immunoglobulin Variable Region -- toxicity KW - Neoplasms, Experimental -- therapy KW - Isoelectric Point KW - Immunoglobulin Variable Region -- chemistry KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Mutagenesis KW - Recombinant Proteins -- toxicity KW - Alanine Transaminase -- blood KW - Disulfides -- chemistry KW - Neoplasms, Experimental -- immunology KW - Liver -- drug effects KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Disulfides -- toxicity KW - Female KW - Immunotoxins -- pharmacokinetics KW - Immunotoxins -- toxicity KW - Immunoglobulin Fragments -- genetics KW - Exotoxins -- chemistry KW - Exotoxins -- pharmacokinetics KW - Immunoglobulin Fragments -- chemistry KW - Immunotoxins -- chemistry KW - Exotoxins -- toxicity KW - Immunotoxins -- genetics KW - Immunoglobulin Fragments -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70978842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Lowering+the+isoelectric+point+of+the+Fv+portion+of+recombinant+immunotoxins+leads+to+decreased+nonspecific+animal+toxicity+without+affecting+antitumor+activity.&rft.au=Onda%2C+M%3BNagata%2C+S%3BTsutsumi%2C+Y%3BVincent%2C+J+J%3BWang+%2C+Q%3BKreitman%2C+R+J%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Onda&rft.aufirst=M&rft.date=2001-07-01&rft.volume=61&rft.issue=13&rft.spage=5070&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling. AN - 70977234; 11435465 AB - Adenosine deaminase (ADA) deficiency in humans results in a severe combined immunodeficiency (SCID). This immunodeficiency is associated with severe disturbances in purine metabolism that are thought to mediate lymphotoxicity. The recent generation of ADA-deficient (ADA(-/-)) mice has enabled the in vivo examination of mechanisms that may underlie the SCID resulting from ADA deficiency. We demonstrate severe depletion of T and B lymphocytes and defects in T and B cell development in ADA(-/-) mice. T cell apoptosis was abundant in thymi of ADA(-/-) mice, but no increase in apoptosis was detected in the spleen and lymph nodes of these animals, suggesting that the defect is specific to developing thymocytes. Studies of mature T cells recovered from spleens of ADA(-/-) mice revealed that ADA deficiency is accompanied by TCR activation defects of T cells in vivo. Furthermore, ex vivo experiments on ADA(-/-) T cells demonstrated that elevated adenosine is responsible for this abnormal TCR signaling. These findings suggest that the metabolic disturbances seen in ADA(-/-) mice affect various signaling pathways that regulate thymocyte survival and function. Experiments with thymocytes ex vivo confirmed that ADA deficiency reduces tyrosine phosphorylation of TCR-associated signaling molecules and blocks TCR-triggered calcium increases. JF - The Journal of clinical investigation AU - Apasov, S G AU - Blackburn, M R AU - Kellems, R E AU - Smith, P T AU - Sitkovsky, M V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 131 EP - 141 VL - 108 IS - 1 SN - 0021-9738, 0021-9738 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, T-Lymphocyte KW - CD69 antigen KW - Deoxyadenine Nucleotides KW - Deoxyadenosines KW - Lectins, C-Type KW - Receptor-CD3 Complex, Antigen, T-Cell KW - Receptors, Interleukin-2 KW - Adenosine Deaminase KW - EC 3.5.4.4 KW - Adenosine KW - K72T3FS567 KW - 2'-deoxyadenosine triphosphate KW - K8KCC8SH6N KW - 2'-deoxyadenosine KW - P582C98ULC KW - Abridged Index Medicus KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Antigens, CD -- biosynthesis KW - Animals KW - B-Lymphocytes -- pathology KW - Apoptosis KW - Antigens, Differentiation, T-Lymphocyte -- biosynthesis KW - Antigens, CD -- genetics KW - Receptors, Interleukin-2 -- genetics KW - Deoxyadenine Nucleotides -- metabolism KW - Mice, Knockout KW - Lymphocyte Activation KW - Phosphorylation KW - Spleen -- immunology KW - Gene Expression Regulation KW - Calcium Signaling KW - Lymph Nodes -- immunology KW - Receptors, Interleukin-2 -- biosynthesis KW - Protein Processing, Post-Translational KW - Lymph Nodes -- pathology KW - Spleen -- pathology KW - Cell Differentiation KW - Mice KW - Organ Specificity KW - Antigens, Differentiation, T-Lymphocyte -- genetics KW - Adenosine -- pharmacology KW - Cells, Cultured KW - Deoxyadenosines -- pharmacology KW - Mice, SCID KW - Severe Combined Immunodeficiency -- pathology KW - Adenosine Deaminase -- deficiency KW - Receptor-CD3 Complex, Antigen, T-Cell -- metabolism KW - Thymus Gland -- pathology KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- pathology KW - Receptor-CD3 Complex, Antigen, T-Cell -- immunology KW - Thymus Gland -- drug effects KW - T-Lymphocytes -- immunology KW - Signal Transduction KW - Severe Combined Immunodeficiency -- genetics KW - Severe Combined Immunodeficiency -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70977234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Adenosine+deaminase+deficiency+increases+thymic+apoptosis+and+causes+defective+T+cell+receptor+signaling.&rft.au=Apasov%2C+S+G%3BBlackburn%2C+M+R%3BKellems%2C+R+E%3BSmith%2C+P+T%3BSitkovsky%2C+M+V&rft.aulast=Apasov&rft.aufirst=S&rft.date=2001-07-01&rft.volume=108&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1995 Jul 15;155(2):536-44 [7608534] Methods Cell Biol. 1995;46:29-39 [7541886] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8373-7 [7667298] J Biol Chem. 1995 Oct 13;270(41):23891-4 [7592575] J Exp Med. 1995 Nov 1;182(5):1545-56 [7595224] J Biol Chem. 1996 Jun 21;271(25):15203-10 [8663040] Cell. 1996 Jul 12;86(1):147-57 [8689682] J Pediatr. 1997 Mar;130(3):378-87 [9063412] Annu Rev Immunol. 1997;15:371-404 [9143693] J Immunol. 1997 Jun 1;158(11):5095-105 [9164924] Blood. 1997 Aug 15;90(4):1600-10 [9269779] J Biol Chem. 1997 Oct 10;272(41):25881-9 [9325320] Eur J Immunol. 1997 Sep;27(9):2366-74 [9341782] J Biol Chem. 1998 Feb 27;273(9):5093-100 [9478961] J Immunol. 1998 Jun 15;160(12):5807-14 [9637491] Blood. 2000 Jun 15;95(12):3859-67 [10845921] J Biol Chem. 2000 Oct 13;275(41):32114-21 [10908569] J Clin Invest. 2000 Nov;106(9):1149-57 [11067867] Lancet. 1972 Nov 18;2(7786):1067-9 [4117384] Exp Cell Res. 1972 Dec;75(2):307-13 [4566303] Lancet. 1975 May 3;1(7914):1010-3 [48676] Cell. 1978 Jun;14(2):365-75 [208780] J Clin Invest. 1979 Apr;63(4):807-11 [312296] Adv Exp Med Biol. 1980;122A:421-5 [7424659] Ann N Y Acad Sci. 1985;451:34-41 [3878120] J Immunol. 1986 Aug 1;137(3):952-61 [2424993] J Biol Chem. 1990 Mar 25;265(9):5280-4 [1690738] Biol Reprod. 1991 Jan;44(1):171-84 [2015347] Int J Cancer Suppl. 1992;7:39-41 [1428401] Cytometry. 1992;13(8):795-808 [1333943] Exp Nephrol. 1993 Mar-Apr;1(2):83-9 [8081961] J Biol Chem. 1994 Sep 23;269(38):23642-7 [7522230] Annu Rev Pharmacol Toxicol. 1995;35:581-606 [7598508] Int Immunol. 1999 Feb;11(2):179-89 [10069416] J Immunol. 1999 Apr 1;162(7):3840-50 [10201901] Annu Rev Immunol. 1999;17:829-74 [10358775] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis. AN - 70975235; 11431698 AB - Breast cancer is a chief cause of cancer-related mortality that affects women worldwide. About 8% of cases are hereditary, and approximately half of these are associated with germline mutations of the breast tumor suppressor gene BRCA1 (refs. 1,2). We have previously reported a mouse model in which Brca1 exon 11 is eliminated in mammary epithelial cells through Cre-mediated excision. This mutation is often accompanied by alterations in transformation-related protein 53 (Trp53, encoding p53), which substantially accelerates mammary tumor formation. Here, we sought to elucidate the underlying mechanism(s) using mice deficient in the Brca1 exon 11 isoform (Brca1Delta11/Delta11). Brca1Delta11/Delta11 embryos died late in gestation because of widespread apoptosis. Unexpectedly, elimination of one Trp53 allele completely rescues this embryonic lethality and restores normal mammary gland development. However, most female Brca1Delta11/Delta11 Trp53+/- mice develop mammary tumors with loss of the remaining Trp53 allele within 6-12 months. Lymphoma and ovarian tumors also occur at lower frequencies. Heterozygous mutation of Trp53 decreases p53 and results in attenuated apoptosis and G1-S checkpoint control, allowing Brca1Delta11/Delta11 cells to proliferate. The p53 protein regulates Brca1 transcription both in vitro and in vivo, and Brca1 participates in p53 accumulation after gamma-irradiation through regulation of its phosphorylation and Mdm2 expression. These findings provide a mechanism for BRCA1-associated breast carcinogenesis. JF - Nature genetics AU - Xu, X AU - Qiao, W AU - Linke, S P AU - Cao, L AU - Li, W M AU - Furth, P A AU - Harris, C C AU - Deng, C X AD - Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 10/9N105, Bethesda, Maryland, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 266 EP - 271 VL - 28 IS - 3 SN - 1061-4036, 1061-4036 KW - Protein Isoforms KW - 0 KW - Index Medicus KW - Ovarian Neoplasms -- etiology KW - Animals KW - Lymphoma -- etiology KW - Exons KW - Ovarian Neoplasms -- genetics KW - Mammary Glands, Animal -- growth & development KW - Mice KW - Mice, Mutant Strains KW - Lymphoma -- genetics KW - Genes, Lethal KW - Mutation KW - Female KW - Sequence Deletion KW - Mammary Neoplasms, Animal -- etiology KW - Apoptosis -- genetics KW - Genes, p53 KW - Mammary Neoplasms, Animal -- genetics KW - Genes, BRCA1 KW - Cell Cycle -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70975235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Genetic+interactions+between+tumor+suppressors+Brca1+and+p53+in+apoptosis%2C+cell+cycle+and+tumorigenesis.&rft.au=Xu%2C+X%3BQiao%2C+W%3BLinke%2C+S+P%3BCao%2C+L%3BLi%2C+W+M%3BFurth%2C+P+A%3BHarris%2C+C+C%3BDeng%2C+C+X&rft.aulast=Xu&rft.aufirst=X&rft.date=2001-07-01&rft.volume=28&rft.issue=3&rft.spage=266&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents. AN - 70947126; 11418304 AB - Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA damaging chemotherapeutics. Moreover, targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin containing immunotoxins. JF - Critical reviews in oncology/hematology AU - Newton, D L AU - Hansen, H J AU - Liu, H AU - Ruby, D AU - Iordanov, M S AU - Magun, B E AU - Goldenberg, D M AU - Rybak, S M AD - SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Room 162, Building 567, Frederick, MD 21702-1201, USA. PY - 2001 SP - 79 EP - 86 VL - 39 IS - 1-2 SN - 1040-8428, 1040-8428 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - Antigens, Neoplasm KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - RNA KW - 63231-63-0 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - RNA -- metabolism KW - Humans KW - Antigens, Neoplasm -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- chemistry KW - Lymphoma, B-Cell -- drug therapy KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Ribonucleases -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70947126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oncology%2Fhematology&rft.atitle=Specifically+targeting+the+CD22+receptor+of+human+B-cell+lymphomas+with+RNA+damaging+agents.&rft.au=Newton%2C+D+L%3BHansen%2C+H+J%3BLiu%2C+H%3BRuby%2C+D%3BIordanov%2C+M+S%3BMagun%2C+B+E%3BGoldenberg%2C+D+M%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=2001-07-01&rft.volume=39&rft.issue=1-2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncology%2Fhematology&rft.issn=10408428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-14 N1 - Date created - 2001-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of PPAR activators on cytokine-stimulated cyclooxygenase-2 expression in human colorectal carcinoma cells. AN - 70934213; 11412039 AB - Cyclooxygenase-2 (COX-2) expression is up-regulated in colorectal cancer tissue. Peroxisome proliferator-activated receptors (PPARs) are expressed in human colorectal tissue and activation of PPARs can alter COX-2 expression. In macrophages, activation of PPARs down-regulates COX-2 expression. We examined the effect of PPARalpha and PPARgamma ligands on untreated and TNF-alpha-induced COX-2 expression in the human colorectal epithelial cell line HT-29. The expression of PPARalpha and PPARgamma was confirmed in these cells. TNF-alpha, an inflammatory cytokine, increased COX-2 expression via the NFkappaB pathway. In the absence of TNF-alpha, WY14643 (PPARalpha activator) caused an increase, while BRL49653 (PPARgamma activator) did not alter COX-2 expression. When HT-29 cells were incubated with TNF-alpha and WY14643, a further increase in COX-2 expression was detected. Incubation with TNF-alpha and BRL49653 caused an additional twofold increase in COX-2 expression. Our results suggest that both PPARalpha signaling and TNF-alpha signaling increase COX-2 expression by independent pathways, while PPARgamma stimulates COX-2 expression by up-regulation of the TNF-alpha pathway. JF - Experimental cell research AU - Ikawa, H AU - Kameda, H AU - Kamitani, H AU - Baek, S J AU - Nixon, J B AU - Hsi, L C AU - Eling, T E AD - Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, 111 T W. Alexander Drive, Research Triangle Park, North Carolina, 27709, USA. Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 73 EP - 80 VL - 267 IS - 1 SN - 0014-4827, 0014-4827 KW - Isoenzymes KW - 0 KW - Ligands KW - Membrane Proteins KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Thiazoles KW - Thiazolidinediones KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - rosiglitazone KW - 05V02F2KDG KW - pirinixic acid KW - 86C4MRT55A KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Thiazoles -- pharmacology KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Regulation, Enzymologic KW - Receptor Cross-Talk KW - Humans KW - Pyrimidines -- pharmacology KW - HT29 Cells KW - Models, Biological KW - Signal Transduction KW - Adenocarcinoma -- enzymology KW - Receptors, Cytoplasmic and Nuclear -- agonists KW - Transcription Factors -- agonists KW - Isoenzymes -- biosynthesis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Colorectal Neoplasms -- enzymology KW - Isoenzymes -- genetics KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70934213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Effect+of+PPAR+activators+on+cytokine-stimulated+cyclooxygenase-2+expression+in+human+colorectal+carcinoma+cells.&rft.au=Ikawa%2C+H%3BKameda%2C+H%3BKamitani%2C+H%3BBaek%2C+S+J%3BNixon%2C+J+B%3BHsi%2C+L+C%3BEling%2C+T+E&rft.aulast=Ikawa&rft.aufirst=H&rft.date=2001-07-01&rft.volume=267&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutator effects of overproducing DNA polymerase eta (Rad30) and its catalytically inactive variant in yeast. AN - 70925806; 11406177 AB - DNA polymerase eta synthesizes DNA in vitro with low fidelity. Based on this, here we report the effects of deletion or increased expression of yeast RAD30 gene, encoding for polymerase eta (Pol eta), on spontaneous mutagenesis in vivo. Deletion of RAD30 did not affect spontaneous mutagenesis. Overproduction of Rad30p was slightly mutagenic in a wild-type yeast strain and moderately mutagenic in strains with inactive 3'-->5'-exonuclease of DNA polymerase epsilon or DNA mismatch repair. These data suggest that excess Rad30p reduces replication fidelity in vivo and that the induced errors may be corrected by exonucleolytic proofreading and DNA mismatch repair. However, the magnitude of mutator effect (only up to 10-fold) suggests that the replication fork is protected from inaccurate synthesis by Pol eta in the absence of DNA damage. Overproduction of catalytically inactive Rad30p was also mutagenic, suggesting that much of the mutator effect results from indirect perturbation of replication rather than from direct misincorporation by Pol eta. Moreover, while excess wild-type Pol eta primarily induced base substitutions in the msh6 and pms1 strains, excess inactive Rad30p induced both base substitutions and frameshifts. This suggests that more than one mutagenic mechanism is operating when RAD30 is overexpressed. JF - Mutation research AU - Pavlov, Y I AU - Nguyen, D AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Natioanl Institutes of Health, Research Triangle Park, NC 27709, USA. pavlov@niehs.nih.gov Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 129 EP - 139 VL - 478 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Recombinant Fusion Proteins KW - 0 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Glucose KW - IY9XDZ35W2 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Genetic Variation KW - Ultraviolet Rays KW - Gene Frequency KW - Cell Division -- drug effects KW - Dose-Response Relationship, Radiation KW - Mutagenesis KW - Gene Deletion KW - Recombinant Fusion Proteins -- metabolism KW - Genotype KW - Base Sequence KW - Recombinant Fusion Proteins -- drug effects KW - Glucose -- pharmacology KW - Recombinant Fusion Proteins -- genetics KW - Point Mutation KW - Galactose -- pharmacology KW - Mutation KW - Cell Division -- genetics KW - Catalysis KW - Cell Division -- radiation effects KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- growth & development KW - Saccharomyces cerevisiae -- enzymology KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70925806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mutator+effects+of+overproducing+DNA+polymerase+eta+%28Rad30%29+and+its+catalytically+inactive+variant+in+yeast.&rft.au=Pavlov%2C+Y+I%3BNguyen%2C+D%3BKunkel%2C+T+A&rft.aulast=Pavlov&rft.aufirst=Y&rft.date=2001-07-01&rft.volume=478&rft.issue=1-2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hamster and rat fetal cells have low spontaneous mutation frequencies and rates. AN - 70923569; 11406169 AB - Somatic cells of whole Syrian hamster fetuses (gestation day 13) were isolated and tested by an in vivo/in vitro mutation assay for spontaneous mutation frequencies using independent 6-thioguanine (6-TG), diphtheria toxin (DT), and ouabain mutation selection systems. Optimum conditions were ascertained. For 6-TG mutants, a total of 21 mutants were found in cells from 24 litters on 1993 plates, for an overall mutant frequency of 1.8 x 10(-7) per viable cell with 12 positive litters. In all, 26 litters were tested using DT; 77 mutants were found in 840 plates, yielding an overall mutant frequency of 2.6 x 10(-7), with 20 positive litters. No correlations or familial effects were found among 23 litters tested for both DT and 6-TG. Of 14 litters which were tested for ouabain mutants, 4 were positive, with a total of 5 mutants found on 988 plates, for an overall mutant frequency of 7.6 x 10(-8). For 14 F344 rat fetuses, the overall 6-TG spontaneous mutation frequency was determined to be 1.6 x 10(-7). From the data, estimates of mutation rates were calculated. For mutation to 6-TG resistance the rate was 8.3 x 10(-8), for mutation to DT resistance the rate was 8.1 x 10(-8) and for ouabain, the spontaneous mutation rate was 5.7 x 10(-8). For F344 rat, the spontaneous mutation rate was 1.1 x 10(-7). Induced mutant frequencies after in utero exposure to 1 mmol/kg N-ethyl-N-nitrosourea (ENU) were 311, 135 and 200 times the spontaneous value for 6-TG, DT and ouabain, respectively, for Syrian hamster fetal cells and 125 times the spontaneous 6-TG value for fetal F344 rat cells. Both spontaneous mutation frequencies and underlying spontaneous mutation rates are low, consistent with the view that fetal cells exercise extremely tight control over DNA fidelity. JF - Mutation research AU - Donovan, P J AU - Smith, G T AU - Riggs, C W AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Building 538, Room 205E, Frederick, MD 21702-1201, USA. donovapa@mail.ncifcrf.gov Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 51 EP - 63 VL - 478 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Diphtheria Toxin KW - 0 KW - 2-Aminopurine KW - 452-06-2 KW - 2,6-diaminopurine KW - 49P95BAU4Z KW - Ouabain KW - 5ACL011P69 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Fetus KW - Animals KW - Thioguanine -- toxicity KW - Gene Frequency KW - Brain -- cytology KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Diphtheria Toxin -- toxicity KW - Drug Resistance KW - Pregnancy KW - Rats KW - Rats, Inbred F344 KW - Breeding KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Brain -- embryology KW - Mesocricetus KW - Ouabain -- toxicity KW - Male KW - Female KW - Cricetinae KW - Mutation -- drug effects KW - Mutation -- genetics KW - 2-Aminopurine -- toxicity KW - 2-Aminopurine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70923569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Hamster+and+rat+fetal+cells+have+low+spontaneous+mutation+frequencies+and+rates.&rft.au=Donovan%2C+P+J%3BSmith%2C+G+T%3BRiggs%2C+C+W&rft.aulast=Donovan&rft.aufirst=P&rft.date=2001-07-01&rft.volume=478&rft.issue=1-2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenesis bioassays: study duration and biological relevance. AN - 70917732; 11397520 AB - Criticisms of the scientific value of rodent carcinogenicity bioassays have focused on the arguments that the studies are too long and that most organ-specific carcinogenic effects observed in experimental animals have little or no relevance to humans. For example, Davies et al. (Davies, T.S., Lynch, B.S., Monro, A.M., Munro, I.C., Nestmann, E.R., 2000. Rodent carcinogenicity tests need be no longer than 18 months: an analysis based on 210 chemicals in the IARC Monographs. Food and Chemical Toxicology 38, 219-235) concluded that the duration of rodent bioassays should be no more than 18 months, based on their analysis of 210 International Agency for Research on Cancer (IARC) rodent carcinogens in which they report that most chemicals showed "tumorigenic effects" at or before 12 months. However, many of these "tumorigenic effects" reflect the occurrence of a single neoplasm, with most tumors occurring much later in the study. Reliance on a single tumor at an early time point as providing definitive evidence of rodent carcinogenicity is a dangerous practice that could produce both false positive and false negative outcomes. An extensive evaluation of the NTP database reveals that many rodent carcinogens produce later-appearing tumors that would not be detected as statistically significant in a 12-18 month study. Such a shortened duration study would be roughly equivalent to evaluating human cancer in subjects 30-50 years of age, which would result in markedly reduced study sensitivity. In fact, many investigators recommend extending the duration of rodent studies to 30 months or to a true lifetime to increase study sensitivity. We also do not agree with the second conclusion of Davies et al. (2000) that the mode of action of rodent carcinogenesis is sufficiently well understood to justify discounting the majority of organ-specific carcinogenic effects found in these studies. The consequences of performing rodent carcinogenicity studies with inadequate sensitivity, and then discounting most of the carcinogenic effects that are observed will be that potential human carcinogens will not be detected, thus forcing near total reliance on human studies for this purpose. This is not prudent public health policy. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Haseman, J AU - Melnick, R AU - Tomatis, L AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 739 EP - 744 VL - 39 IS - 7 SN - 0278-6915, 0278-6915 KW - Carcinogens KW - 0 KW - Index Medicus KW - United States KW - Rats KW - Models, Animal KW - Animals KW - Mice KW - Public Policy KW - Maximum Tolerated Dose KW - Time Factors KW - Species Specificity KW - Male KW - Female KW - Risk Assessment KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70917732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Carcinogenesis+bioassays%3A+study+duration+and+biological+relevance.&rft.au=Haseman%2C+J%3BMelnick%2C+R%3BTomatis%2C+L%3BHuff%2C+J&rft.aulast=Haseman&rft.aufirst=J&rft.date=2001-07-01&rft.volume=39&rft.issue=7&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depression: a major, unrecognized risk factor for osteoporosis? AN - 70912828; 11397644 AB - Existing studies of the relationship between depression and osteoporosis have been heterogeneous in their design and use of diagnostic instruments for depression, which might have contributed to the different results on the comorbidity of these two conditions. Nevertheless, these studies reveal a strong association between depression and osteoporosis. Endocrine factors such as depression-induced hypersecretion of corticotropin-releasing hormone and hypercortisolism, hypogonadism, growth hormone deficiency and increased concentration of circulating interleukin 6, might play a crucial role in the bone loss observed in subjects suffering from major depression. JF - Trends in endocrinology and metabolism: TEM AU - Cizza, G AU - Ravn, P AU - Chrousos, G P AU - Gold, P W AD - Clinical Neuroendocrinology Branch, NIMH, Bethesda, MD, USA. gcizza@codon.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 198 EP - 203 VL - 12 IS - 5 SN - 1043-2760, 1043-2760 KW - Antidepressive Agents KW - 0 KW - Psychotropic Drugs KW - Index Medicus KW - Fractures, Bone -- physiopathology KW - Cross-Sectional Studies KW - Fractures, Bone -- metabolism KW - Risk Factors KW - Humans KW - Fractures, Bone -- etiology KW - Cohort Studies KW - Psychotropic Drugs -- therapeutic use KW - Bone Density KW - Antidepressive Agents -- therapeutic use KW - Psychotropic Drugs -- adverse effects KW - Antidepressive Agents -- adverse effects KW - Depression -- physiopathology KW - Depression -- complications KW - Depression -- metabolism KW - Osteoporosis -- etiology KW - Depression -- drug therapy KW - Osteoporosis -- physiopathology KW - Osteoporosis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70912828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.atitle=Depression%3A+a+major%2C+unrecognized+risk+factor+for+osteoporosis%3F&rft.au=Cizza%2C+G%3BRavn%2C+P%3BChrousos%2C+G+P%3BGold%2C+P+W&rft.aulast=Cizza&rft.aufirst=G&rft.date=2001-07-01&rft.volume=12&rft.issue=5&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.issn=10432760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. AN - 70908700; 11390663 AB - Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Delta strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Delta mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells. JF - Molecular and cellular biology AU - Natarajan, K AU - Meyer, M R AU - Jackson, B M AU - Slade, D AU - Roberts, C AU - Hinnebusch, A G AU - Marton, M J AD - Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 4347 EP - 4368 VL - 21 IS - 13 SN - 0270-7306, 0270-7306 KW - Amino Acids KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - Mutagens KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Glycogen KW - 9005-79-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Protein Kinases KW - EC 2.7.- KW - Amitrole KW - ZF80H5GXUF KW - Index Medicus KW - Trans-Activators -- metabolism KW - Peroxisomes -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Mutagens -- pharmacology KW - Methyl Methanesulfonate -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Genes, Reporter -- genetics KW - Glycogen -- metabolism KW - Trans-Activators -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Mitochondria -- metabolism KW - Peroxisomes -- genetics KW - Promoter Regions, Genetic -- genetics KW - Amitrole -- pharmacology KW - Mitochondria -- genetics KW - Models, Theoretical KW - Amino Acids -- genetics KW - Amino Acids -- biosynthesis KW - DNA-Binding Proteins -- genetics KW - Fungal Proteins -- genetics KW - Gene Expression Regulation, Fungal -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Gene Expression Profiling KW - Protein Kinases -- metabolism KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- physiology KW - Protein Kinases -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70908700?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Transcriptional+profiling+shows+that+Gcn4p+is+a+master+regulator+of+gene+expression+during+amino+acid+starvation+in+yeast.&rft.au=Natarajan%2C+K%3BMeyer%2C+M+R%3BJackson%2C+B+M%3BSlade%2C+D%3BRoberts%2C+C%3BHinnebusch%2C+A+G%3BMarton%2C+M+J&rft.aulast=Natarajan&rft.aufirst=K&rft.date=2001-07-01&rft.volume=21&rft.issue=13&rft.spage=4347&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1980 Sep;143(3):1384-94 [6997270] J Bacteriol. 1982 May;150(2):969-72 [7040348] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6442-6 [6387704] Mol Cell Biol. 1984 Dec;4(12):2767-73 [6152013] Cell. 1986 Apr 25;45(2):201-7 [3516411] Science. 1986 Oct 24;234(4775):451-7 [3532321] Proc Natl Acad Sci U S A. 1986 Nov;83(22):8516-20 [3464968] Nucleic Acids Res. 1987 Jul 10;15(13):5261-73 [3299266] Science. 1987 Aug 21;237(4817):874-80 [3303332] Eur J Biochem. 1988 Jan 15;171(1-2):171-6 [3123231] Mol Cell Biol. 1989 Jul;9(7):2944-9 [2674675] Science. 1989 Nov 17;246(4932):931-5 [2683089] Curr Genet. 1990 Feb;17(2):105-11 [2182197] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] Nature. 1990 Jul 26;346(6282):329-31 [2142753] Mol Gen Genet. 1990 Oct;224(1):57-64 [2277632] Mol Cell Biol. 1991 May;11(5):2723-35 [2017175] FEBS Lett. 1998 Mar 13;424(3):127-30 [9539135] Curr Opin Genet Dev. 1998 Apr;8(2):185-93 [9610409] Nat Biotechnol. 1996 Dec;14(13):1675-80 [9634850] J Bacteriol. 1998 Jul;180(14):3533-40 [9657994] EMBO J. 1998 Jul 15;17(14):4086-91 [9670023] FEBS Lett. 1998 Jun 23;430(1-2):116-25 [9678606] Mol Gen Genet. 1998 Aug;259(3):246-55 [9749667] Science. 1998 Oct 23;282(5389):699-705 [9784122] Nat Biotechnol. 1998 Oct;16(10):939-45 [9788350] J Bacteriol. 1998 Nov;180(21):5718-26 [9791124] Nat Med. 1998 Nov;4(11):1293-301 [9809554] EMBO J. 1998 Dec 1;17(23):6924-31 [9843498] J Biol Chem. 1999 Jan 22;274(4):2014-20 [9890959] Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1486-91 [9990050] J Nutr. 1999 Feb;129(2):325-7 [10024608] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2937-42 [10077615] Eur J Biochem. 1999 Apr;261(1):163-70 [10103047] Mol Cell Biol. 1999 May;19(5):3360-71 [10207060] Mol Cell Biol. 1992 Dec;12(12):5700-10 [1333044] Mol Cell Biol. 1993 Jun;13(6):3541-56 [8497269] Mol Cell Biol. 1988 May;8(5):2132-9 [3290651] FEBS Lett. 1988 Dec 5;241(1-2):83-8 [2848727] J Biol Chem. 1999 Apr 30;274(18):12480-7 [10212224] Biochem J. 1999 Jun 15;340 ( Pt 3):855-62 [10359673] J Biol Chem. 1999 Aug 6;274(32):22184-90 [10428783] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9374-8 [10430950] J Biol Chem. 1999 Aug 13;274(33):23565-9 [10438537] Yeast. 1999 Sep 30;15(13):1365-75 [10509018] J Biol Chem. 1991 Oct 25;266(30):20453-6 [1939099] Microbiol Rev. 1991 Sep;55(3):349-70 [1943992] Mol Microbiol. 1991 Sep;5(9):2143-52 [1837329] J Bacteriol. 1992 Jun;174(12):4148-56 [1350780] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6746-50 [1495962] Cell. 1992 Aug 21;70(4):647-57 [1505029] J Biol Chem. 1993 Jun 5;268(16):12116-22 [8099357] Mol Cell Biol. 1993 Aug;13(8):5099-111 [8336737] J Bacteriol. 1993 Sep;175(17):5548-58 [8366040] Mol Microbiol. 1993 Jul;9(1):221-3 [8412668] Mol Cell Biol. 1994 Mar;14(3):1920-8 [8114723] Cell. 1994 May 6;77(3):381-90 [8181058] Mol Cell Biol. 1995 Apr;15(4):1879-88 [7891681] EMBO J. 1995 Jul 3;14(13):3184-99 [7621831] Mol Cell Biol. 1995 Aug;15(8):4497-506 [7623840] Science. 1995 Oct 20;270(5235):467-70 [7569999] Curr Genet. 1995 May;27(6):501-8 [7553933] EMBO J. 1996 Jun 17;15(12):2924-34 [8670793] J Biol Chem. 1996 Oct 4;271(40):24989-94 [8798780] J Biol Chem. 1996 Oct 4;271(40):25011-8 [8798783] J Biol Chem. 1996 Nov 22;271(47):29637-43 [8939895] Mol Microbiol. 1996 Nov;22(4):681-92 [8951815] Mol Cell Biol. 1997 Jan;17(1):69-80 [8972187] Eur J Biochem. 1997 Apr 15;245(2):289-93 [9151955] J Biol Chem. 1997 Aug 29;272(35):21661-4 [9268289] J Biol Chem. 1997 Sep 12;272(37):23224-30 [9287330] Science. 1997 Oct 24;278(5338):680-6 [9381177] Nucleic Acids Res. 1998 Jan 1;26(1):33-7 [9399795] Microbiol Mol Biol Rev. 1997 Dec;61(4):503-32 [9409150] Mol Gen Genet. 1998 Jan;257(2):230-7 [9491082] Mol Gen Genet. 1998 Jan;257(2):238-48 [9491083] Genetics. 1998 May;149(1):57-72 [9584086] J Biol Chem. 1998 May 22;273(21):12696-702 [9582292] Philos Trans R Soc Lond B Biol Sci. 1999 Sep 29;354(1389):1577-80; discussion 1580-1 [10582243] Nucleic Acids Res. 2000 Jan 1;28(1):73-6 [10592185] Annu Rev Cell Dev Biol. 1999;15:291-339 [10611964] Mol Cell Biol. 2000 Jan;20(2):634-47 [10611242] Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14866-70 [10611304] Genes Dev. 1999 Dec 15;13(24):3271-9 [10617575] EMBO J. 2000 Jan 17;19(2):282-94 [10637232] J Mol Biol. 2000 Mar 10;296(5):1205-14 [10698627] Mol Cell Biol. 2000 Apr;20(8):2706-17 [10733573] FEBS Lett. 2000 Mar 24;470(2):156-60 [10734226] EMBO J. 2000 Apr 17;19(8):1887-99 [10775272] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5984-8 [10811893] Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7957-62 [10884426] Nat Genet. 2000 Jul;25(3):333-7 [10888885] Cell. 2000 Jul 7;102(1):109-26 [10929718] Physiol Genomics. 2000 Aug 9;3(2):83-92 [11015603] Mol Cell Biol. 2000 Nov;20(21):8157-67 [11027285] J Biol Chem. 2000 Oct 13;275(41):32310-6 [10922376] Science. 2000 Dec 1;290(5497):1717-21 [11099404] Mol Biol Cell. 2000 Dec;11(12):4241-57 [11102521] FEMS Microbiol Rev. 2001 Jan;25(1):125-45 [11152943] J Bacteriol. 2001 Apr;183(7):2331-4 [11244074] Nat Biotechnol. 2001 Apr;19(4):342-7 [11283592] Biochem J. 1966 Jun;99(3):513-20 [5964954] J Gen Microbiol. 1968 Apr;51(1):49-56 [5653230] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-linked glycosylation sites adjacent to and within the V1/V2 and the V3 loops of dualtropic human immunodeficiency virus type 1 isolate DH12 gp120 affect coreceptor usage and cellular tropism. AN - 70891959; 11390601 AB - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is extensively glycosylated, containing approximately 23 asparagine (N)-linked glycosylation sites on its gp120 subunit. In this study, specific glycosylation sites on gp120 of a dualtropic primary HIV-1 isolate, DH12, were eliminated by site-directed mutagenesis and the properties of the resulting mutant envelopes were evaluated using a recombinant vaccinia virus-based cell-to-cell fusion assay alone or in the context of viral infections. Of the glycosylation sites that were evaluated, those proximal to the V1/V2 loops (N135, N141, N156, N160) and the V3 loops (N301) of gp120 were functionally critical. The glycosylation site mutations near the V1/V2 loop compromised the use of CCR5 and CXCR4 equally. In contrast, a mutation within the V3 loop preferentially inhibited the usage of CCR5; although this mutant protein completely lost its CCR5-dependent fusion activity, it retained 50% of the wild-type fusion activity with CXCR4. The replication of a virus containing this mutation was severely compromised in peripheral blood mononuclear cells, MT-4 cells, and primary monocyte-derived macrophages. A revertant virus, which acquired second site changes in the V3 loop that resulted in an increase in net positive charge, was isolated. The revertant virus fully recovered the usage of CXCR4 but not of CCR5, thereby altering the tropism of the parental virus from dualtropic to T-tropic. These results suggest that carbohydrate moieties near the V1/V2 and the V3 loops play critical roles in maintaining proper conformation of the variable loops for optimal interaction with receptors. Our results, combined with those of previously reported studies, further demonstrate that the function of individual glycans may be virus isolate dependent. JF - Journal of virology AU - Ogert, R A AU - Lee, M K AU - Ross, W AU - Buckler-White, A AU - Martin, M A AU - Cho, M W AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-0460, USA. Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 5998 EP - 6006 VL - 75 IS - 13 SN - 0022-538X, 0022-538X KW - HIV Envelope Protein gp120 KW - 0 KW - Receptors, CCR5 KW - Receptors, CXCR4 KW - Index Medicus KW - Virus Replication KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Glycosylation KW - Receptors, CXCR4 -- physiology KW - HIV-1 -- chemistry KW - Receptors, CCR5 -- physiology KW - HIV Envelope Protein gp120 -- chemistry KW - HIV-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70891959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=N-linked+glycosylation+sites+adjacent+to+and+within+the+V1%2FV2+and+the+V3+loops+of+dualtropic+human+immunodeficiency+virus+type+1+isolate+DH12+gp120+affect+coreceptor+usage+and+cellular+tropism.&rft.au=Ogert%2C+R+A%3BLee%2C+M+K%3BRoss%2C+W%3BBuckler-White%2C+A%3BMartin%2C+M+A%3BCho%2C+M+W&rft.aulast=Ogert&rft.aufirst=R&rft.date=2001-07-01&rft.volume=75&rft.issue=13&rft.spage=5998&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1998 May 29;93(5):677-80 [9630212] Cell. 1996 Jun 28;85(7):1135-48 [8674119] J Virol. 1996 Oct;70(10):7318-21 [8794390] Nat Med. 1996 Nov;2(11):1244-7 [8898753] Nature. 1996 Nov 14;384(6605):184-7 [8906796] Nat Med. 1996 Dec;2(12):1293-300 [8946819] Immunol Res. 1997 Feb;16(1):15-28 [9048206] J Virol. 1997 Apr;71(4):3259-62 [9060691] J Virol. 1997 Sep;71(9):7136-9 [9261451] Curr Opin Immunol. 1997 Aug;9(4):551-62 [9287172] Science. 1998 Jun 19;280(5371):1949-53 [9632396] Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7682-6 [9636210] Nature. 1998 Jun 18;393(6686):648-59 [9641677] J Virol. 1998 Oct;72(10):8365-70 [9733886] Virology. 1999 May 10;257(2):290-6 [10329539] FEBS Lett. 1999 Jul 2;454(1-2):47-52 [10413093] FEBS Lett. 1998 Apr 24;426(3):367-72 [9600268] AIDS Res Hum Retroviruses. 2000 May 20;16(8):765-75 [10826483] AIDS. 1999;13 Suppl A:S137-62 [10885772] J Virol. 2000 Aug;74(15):6769-76 [10888615] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] Nature. 1987 Nov 5-11;330(6143):74-7 [2959866] J Virol. 1988 Jan;62(1):139-47 [3257102] Proc Natl Acad Sci U S A. 1987 Nov;84(22):8120-4 [2825177] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9248-52 [3264072] J Virol. 1989 Feb;63(2):639-46 [2536098] Proc Natl Acad Sci U S A. 1989 May;86(9):3384-8 [2541446] AIDS Res Hum Retroviruses. 1990 Jun;6(6):785-94 [2364019] Proc Natl Acad Sci U S A. 1990 Sep;87(17):6574-8 [2395859] Nature. 1990 Nov 1;348(6296):69-73 [2172833] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097-101 [2014229] Science. 1991 Jul 5;253(5015):71-4 [1905842] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7056-60 [1871120] Virology. 1991 Sep;184(1):319-29 [1871974] J Virol. 1991 Nov;65(11):5782-9 [1920616] J Virol. 1992 Jan;66(1):235-43 [1727487] J Virol. 1992 Jan;66(1):305-9 [1727490] J Virol. 1992 Feb;66(2):757-65 [1731110] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2213-7 [1549584] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9434-8 [1409653] AIDS Res Hum Retroviruses. 1992 Aug;8(8):1459-60 [1466982] Virology. 1993 Mar;193(1):483-91 [8438583] AIDS Res Hum Retroviruses. 1993 Jun;9(6):529-39 [8347397] Virology. 1994 Mar;199(2):431-8 [8122371] J Virol. 1998 Mar;72(3):2509-15 [9499115] J Virol. 1998 May;72(5):4478-84 [9557745] Proc Natl Acad Sci U S A. 1998 May 12;95(10):5740-5 [9576954] Virology. 1994 Jul;202(1):129-45 [8009827] J Virol. 1995 Jan;69(1):39-48 [7983734] AIDS Res Hum Retroviruses. 1994 Jul;10(7):803-11 [7986586] J Virol. 1995 Jul;69(7):4413-22 [7769703] J Virol. 1995 Jul;69(7):4453-62 [7769705] J Gen Virol. 1996 Apr;77 ( Pt 4):753-8 [8627264] J Virol. 1996 Sep;70(9):6288-95 [8709256] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Temporal profiling of methamphetamine-induced changes in gene expression in the mouse brain: evidence from cDNA array. AN - 70846869; 11354012 AB - Methamphetamine (METH) is a neurodegenerative drug of abuse. Its toxicity is characterized by destruction of monoaminergic terminals and by apoptosis in cortical and striatal cell bodies. Multiple factors appear to control METH neurotoxicity, including free radicals and transcription factors. Here, using cDNA arrays, we show the temporal profile of gene expression patterns in the cortex of mice treated with this drug. We obtained two patterns of changes from 588 genes surveyed. First, an early pattern is characterized by upregulation of transcription factors, including members of the jun family. Second, a delayed pattern includes genes related to cell death and to DNA repair. A number of trophic factors were also activated at the later timepoint. These observations suggest that METH can activate a multigene machinery that participates in the production of its toxic effects. The resulting degenerative effects of the drug are thus the result of a balance between protoxic and antiapoptotic mechanisms triggered by its administration to these animals. These observations are of clinical relevance because of the recent identification of degenerative changes in the brains of METH abusers. Copyright 2001 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Cadet, J L AU - Jayanthi, S AU - McCoy, M T AU - Vawter, M AU - Ladenheim, B AD - Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 40 EP - 48 VL - 41 IS - 1 SN - 0887-4476, 0887-4476 KW - Central Nervous System Stimulants KW - 0 KW - Transcription Factors KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Animals KW - Transcription Factors -- drug effects KW - Genes, Tumor Suppressor -- drug effects KW - Transcription Factors -- metabolism KW - Oncogenes -- drug effects KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Oncogenes -- physiology KW - Mice KW - Genes, Tumor Suppressor -- physiology KW - Cluster Analysis KW - Male KW - Up-Regulation -- physiology KW - Gene Expression -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Central Nervous System Stimulants -- toxicity KW - Brain -- drug effects KW - Up-Regulation -- drug effects KW - Oligonucleotide Array Sequence Analysis -- methods KW - Methamphetamine -- pharmacology KW - Brain -- metabolism KW - Gene Expression -- physiology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70846869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Temporal+profiling+of+methamphetamine-induced+changes+in+gene+expression+in+the+mouse+brain%3A+evidence+from+cDNA+array.&rft.au=Cadet%2C+J+L%3BJayanthi%2C+S%3BMcCoy%2C+M+T%3BVawter%2C+M%3BLadenheim%2C+B&rft.aulast=Cadet&rft.aufirst=J&rft.date=2001-07-01&rft.volume=41&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conceptualizing the multidimensional nature of self-efficacy: assessment of situational context and level of behavioral challenge to maintain safer sex AN - 57708003; 189391 AB - A. Bandura (1991) argued that selfefficacy measurement should be specific both to the situation in which the behavior occurs and level to challenge in that situation. Measures consistent with the 2 dimensions were developed with graded challenge levels and differing gender-appropriate situations. Participants were 1496 controls in the National Institute of Mental Health Multisite HIV prevention trial recruited from STD clinics and health service centers (925 women and 571 men). 4 separate-sex confirmatory factor analysis models were tested as follows: a) Condom negotiation efficacy as a unitary construct across situations and gradation of difficulty; b) situation as preeminent, which transfers across skills whatever the gradation of difficulty; c) skill as predominant, irrespective of situation; and d) a multidimensional design that simultaneously accounts for both situation and graded difficulty. Consistent with Bandura's theory, the multidimensional model provided the best fit for both samples. (Original abstract - amended) JF - Health Psychology AU - Murphy, D A AU - Stein, J A AU - Schlenger, W AU - Maibach, E AU - National Institute of Mental Health Multisite HIV Prevention Trial Group AD - National Institute of Mental Health Multisite HIV Prevention Trial Group Y1 - 2001/07// PY - 2001 DA - July 2001 SP - 281 EP - 290 VL - 20 IS - 4 SN - 0278-6133, 0278-6133 KW - Structural equation models KW - Selfefficacy KW - Safe sexual practices KW - Human immunodeficiency virus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57708003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Psychology&rft.atitle=Conceptualizing+the+multidimensional+nature+of+self-efficacy%3A+assessment+of+situational+context+and+level+of+behavioral+challenge+to+maintain+safer+sex&rft.au=Murphy%2C+D+A%3BStein%2C+J+A%3BSchlenger%2C+W%3BMaibach%2C+E%3BNational+Institute+of+Mental+Health+Multisite+HIV+Prevention+Trial+Group&rft.aulast=Murphy&rft.aufirst=D&rft.date=2001-07-01&rft.volume=20&rft.issue=4&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Health+Psychology&rft.issn=02786133&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2002-03-11 N1 - Document feature - il. refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Safe sexual practices; Selfefficacy; Structural equation models ER - TY - JOUR T1 - Declining insulin requirement in the late first trimester of diabetic pregnancy AN - 223068379; 11423491 AB - Observations in the Diabetes in Early Pregnancy Study cohort disclosed a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include over-insulinization of previously poorly controlled diabetes, a transient decline in protesters secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. JF - Diabetes Care AU - Jovanovic, Lois AU - Knopp, Robert H AU - Brown, Zane AU - Conley, Mary R AU - et al Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 1130 EP - 6 CY - Alexandria PB - American Diabetes Association VL - 24 IS - 7 SN - 01495992 KW - Medical Sciences--Endocrinology KW - Blood Glucose KW - Hemoglobin A, Glycosylated KW - Insulin KW - Thiobarbituric Acid Reactive Substances KW - Pregnancy KW - Diabetes KW - United States KW - Age Factors KW - Humans KW - Pregnancy in Diabetics -- blood KW - Thiobarbituric Acid Reactive Substances -- analysis KW - Income KW - Smoking KW - Adult KW - Diabetic Retinopathy -- epidemiology KW - Adolescent KW - Educational Status KW - Hemoglobin A, Glycosylated -- analysis KW - Blood Glucose -- metabolism KW - Dose-Response Relationship, Drug KW - Proteinuria -- epidemiology KW - Continental Population Groups KW - Gestational Age KW - Infant, Newborn KW - Alcohol Drinking KW - Socioeconomic Factors KW - Pregnancy Trimester, First KW - Ethnic Groups KW - Diabetes Mellitus, Type 1 -- blood KW - Cohort Studies KW - Female KW - Pregnancy in Diabetics -- drug therapy KW - Diabetes Mellitus, Type 1 -- drug therapy KW - Insulin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223068379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes+Care&rft.atitle=Declining+insulin+requirement+in+the+late+first+trimester+of+diabetic+pregnancy&rft.au=Jovanovic%2C+Lois%3BKnopp%2C+Robert+H%3BBrown%2C+Zane%3BConley%2C+Mary+R%3Bet+al&rft.aulast=Jovanovic&rft.aufirst=Lois&rft.date=2001-07-01&rft.volume=24&rft.issue=7&rft.spage=1130&rft.isbn=&rft.btitle=&rft.title=Diabetes+Care&rft.issn=01495992&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Diabetes Association Jul 2001 N1 - Last updated - 2013-01-27 N1 - CODEN - DICAD2 ER - TY - JOUR T1 - Characterization and localization of cytochrome P450 mediated metabolism of MPTP to nor-MPTP in mouse brain: Relevance to Parkinson's disease AN - 20171404; 10262884 AB - 1-Methyl, 4-phenyl,l,2,5,6,tetrahydropyridine (MPTP) is a dopaminergic toxin which produces Parkinson's disease-like symptoms in primates and dopaminergic cell loss in mice. MPTP is bioactivated through monoamine oxidase to MPP and detoxified by cytochrome P450 to nor-MPTP. We have examined metabolisms of MPTP to nor-MPTP by mouse brain microsomes and compared it with corresponding activity in liver. In brain, but not in liver, this biotransformation was completely abolished by quinidine, an inhibitor of P4502D. Northern blotting experiments demonstrated constitutive expression of cytochrome P4502D in mouse brain. A fluorescencein situ hybridization study of mouse brain showed presence of P4502D mRNA predominantly in neuronal cells within the cortex, hippocampus, thalamus, Purkinje and granule cell layers of the cerebellum and in the reticular neurons of midbrain. Striatal neurons were sparsely stained indicating a relative paucity of expression. These studies demonstrate for the first time that detoxification of MPTP to nor-MPTP occurs in mouse brain through cytochrome P4502D which is primarily localized in neuronal cells. Cytochrome P4502D6 is known to exhibit genetic polymorphism in humans, and a defect in this isoform could potentially lead to decreased detoxification of neurotoxins in certain neuronal sub-population, which in turn may have implications in pathogenesis of Parkinson's disease. JF - Neurotoxicity Research AU - Upadhya, Sudarshan C AU - Boyd, Michael R AU - Ravindranath, Vijayalakshmi AD - Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Hosur Road, 560 029 Bangalore, India, vijir@vsnl.com Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 369 EP - 380 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 3 IS - 4 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Detoxification KW - Hippocampus KW - Amine oxidase (flavin-containing) KW - Gene polymorphism KW - Parkinson's disease KW - biotransformation KW - Cerebellum KW - Thalamus KW - Granule cells KW - Mesencephalon KW - Northern blotting KW - Dopamine KW - Cortex KW - Neostriatum KW - Microsomes KW - MPTP KW - Brain KW - Primates KW - mRNA KW - Neurodegenerative diseases KW - Movement disorders KW - Quinidine KW - Neurons KW - Neurotoxicity KW - Liver KW - Cytochrome P450 KW - Neurotoxins KW - Metabolism KW - N3 11028:Neuropharmacology & toxicology KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20171404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=Characterization+and+localization+of+cytochrome+P450+mediated+metabolism+of+MPTP+to+nor-MPTP+in+mouse+brain%3A+Relevance+to+Parkinson%27s+disease&rft.au=Upadhya%2C+Sudarshan+C%3BBoyd%2C+Michael+R%3BRavindranath%2C+Vijayalakshmi&rft.aulast=Upadhya&rft.aufirst=Sudarshan&rft.date=2001-07-01&rft.volume=3&rft.issue=4&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033198 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Detoxification; Amine oxidase (flavin-containing); Hippocampus; Parkinson's disease; Gene polymorphism; Cerebellum; biotransformation; Thalamus; Granule cells; Northern blotting; Mesencephalon; Cortex; Dopamine; Neostriatum; Microsomes; MPTP; Brain; mRNA; Neurodegenerative diseases; Movement disorders; Neurons; Quinidine; Neurotoxicity; Liver; Cytochrome P450; Neurotoxins; Metabolism; Primates DO - http://dx.doi.org/10.1007/BF03033198 ER - TY - JOUR T1 - Pharmacological and toxicological significance of brain cytochromes P450 AN - 20138605; 10262879 AB - Abstract not available. JF - Neurotoxicity Research AU - Ravindranath, Vijayalakshmi AD - Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Hosur Road, 560 029 Bangalore, India, vijir@vsnl.com Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 321 EP - 328 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 3 IS - 4 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Neurotoxicity KW - Brain KW - Cytochrome P450 KW - N3 11028:Neuropharmacology & toxicology KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20138605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=Pharmacological+and+toxicological+significance+of+brain+cytochromes+P450&rft.au=Ravindranath%2C+Vijayalakshmi&rft.aulast=Ravindranath&rft.aufirst=Vijayalakshmi&rft.date=2001-07-01&rft.volume=3&rft.issue=4&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033193 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Neurotoxicity; Brain; Cytochrome P450 DO - http://dx.doi.org/10.1007/BF03033193 ER - TY - JOUR T1 - Training of providers in embryo transfer: what is the minimum number of transfers required for proficiency? AN - 19784483; 5159605 AB - Embryo transfer represents one of the most critical procedures in the practice of assisted reproduction. The objective of this study was to identify retrospectively the minimum number of embryo transfers required to train providers properly in this skill. The study group consisted of 204 patients who received embryo transfers between January 1996 and March 2000 in a university-based programme of assisted reproduction. The main outcome measure was clinical pregnancies per embryo transfer. Five Fellow trainees performed a total of 204 embryo transfers for an overall pregnancy rate of 45.5% per embryo transfer (93/204). In comparison, the programme pregnancy rate per transfer for experienced providers was 47.3% (560/1179). A chronological graph of each individual trainee's experience for the first 50 embryo transfers performed suggested a lower initial pregnancy rate for three of the five trainees. To determine whether a learning curve might exist, results of the first 25 transfers were compared as a subgroup with the second 25 transfers. Pregnancy rates were lower for the 1-25 transfer subgroup than in the 26-50 subgroup for three of the five Fellow trainees, although the difference was not statistically significant. Clinical pregnancy rates of Fellows-in-training were indistinguishable statistically from those of experienced staff by 50 transfers. JF - Human Reproduction AU - Papageorgiou, T C AU - Hearns-Stokes, R M AU - Leondires, M P AU - Miller, B T AU - Chakraborty, P AU - Cruess, D AU - Segars, J AD - Pediatric and Reproductive Endocrinology Branch, NICHD, Building 10, Room 9D42, NIH, Bethesda, MD 20892, USA, segars@mail.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 1415 EP - 1419 VL - 16 IS - 7 SN - 0268-1161, 0268-1161 KW - reproductive technologies KW - Sustainability Science Abstracts; Human Population KW - Reproduction KW - Embryo transfer KW - Pregnancy KW - M3 1010:Issues in Sustainable Development KW - M1 100:Population Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19784483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Reproduction&rft.atitle=Training+of+providers+in+embryo+transfer%3A+what+is+the+minimum+number+of+transfers+required+for+proficiency%3F&rft.au=Papageorgiou%2C+T+C%3BHearns-Stokes%2C+R+M%3BLeondires%2C+M+P%3BMiller%2C+B+T%3BChakraborty%2C+P%3BCruess%2C+D%3BSegars%2C+J&rft.aulast=Papageorgiou&rft.aufirst=T&rft.date=2001-07-01&rft.volume=16&rft.issue=7&rft.spage=1415&rft.isbn=&rft.btitle=&rft.title=Human+Reproduction&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Embryo transfer; Reproduction; Pregnancy ER - TY - JOUR T1 - Mutagenesis by O super(6)-Methyl-, O super(6)-Ethyl-, and O super(6)-Benzylguanine and O super(4)-Methylthymine in Human Cells: Effects of O super(6)-Alkylguanine-DNA Alkyltransferase and Mismatch Repair AN - 18215308; 5279653 AB - Double-stranded and gapped shuttle vectors were used to study mutagenesis in human cells by O super(6)-methyl (m super(6)G)-, O super(6)-ethyl (e super(6)G)-, and O super(6)-benzylguanine (b super(6)G), and O super(4)-methylthymine (m super(4)T) when these bases were incorporated site-specifically in the ATG initiation codon of a lacZ' gene. Vectors were transfected into either human kidney cells (293) or colon tumor cells (SO) or into mismatch repair defective human colon tumor cells (H6 and LoVo). Cellular O super(6)-alkylguanine-DNA alkyltransferase (alkyltransferase) was optionally inactivated by treating cells with O super(6)-benzylguanine prior to transfection. In alkyltransferase competent cells, the mutagenicity of all the modified bases was substantially higher in gapped plasmids than in double-stranded plasmids. Alkyltransferase inactivation increased mutagenesis by the three O super(6)-substituted guanines in both double-stranded and gapped plasmids but did not affect m super(4)T mutagenesis. In the absence of alkyltransferase, mutagenesis by m super(6)G and to a lesser extent e super(6)G in double-stranded vectors was higher in the mismatch repair defective H6 and LoVo cells than in SO or 293 cells indicating that e super(6)G as well as m super(6)G were subject to mismatch repair processing in these cells. The level of mutagenesis by m super(4)T and b super(6)G was not affected by mismatch repair status. When incorporated in gapped plasmids and in the absence of alkyltransferase, the order of mutagenicity for the modified bases was m super(4)T > e super(6)G approximately equal to m super(6)G > b super(6)G. The O super(6)-substituted guanines primarily produced G arrow right A transitions while m super(4)T primarily produced T arrow right C transitions. However, m super(4)T also produced a significant number of T arrow right A transversion mutations in addition to T arrow right C transitions in mismatch repair deficient LoVo cells. JF - Chemical Research in Toxicology AU - Pauly, G T AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute at Frederick, PO Box B, Frederick, Maryland 21702, USA Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 894 EP - 900 VL - 14 IS - 7 SN - 0893-228X, 0893-228X KW - man KW - LoVo cells KW - alkyltransferase KW - benzylguanine KW - methylthymine KW - Toxicology Abstracts KW - Expression vectors KW - Mutagenicity KW - Transfection KW - DNA repair KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18215308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Mutagenesis+by+O+super%286%29-Methyl-%2C+O+super%286%29-Ethyl-%2C+and+O+super%286%29-Benzylguanine+and+O+super%284%29-Methylthymine+in+Human+Cells%3A+Effects+of+O+super%286%29-Alkylguanine-DNA+Alkyltransferase+and+Mismatch+Repair&rft.au=Pauly%2C+G+T%3BMoschel%2C+R+C&rft.aulast=Pauly&rft.aufirst=G&rft.date=2001-07-01&rft.volume=14&rft.issue=7&rft.spage=894&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA repair; Mutagenicity; Transfection; Expression vectors ER - TY - JOUR T1 - Induction of Hepatic 8-Oxo-deoxyguanosine Adducts by 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Sprague-Dawley Rats Is Female-Specific and Estrogen-Dependent AN - 18211709; 5279647 AB - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a hepatocarcinogen that induces sex-specific hepatic neoplastic alterations in female, but not male, rats. It has been hypothesized that TCDD-induced alterations in estrogen metabolism lead to increased generation of reactive oxygen species. The resulting oxidative damage to DNA may contribute to TCDD-induced tumor promotion and hepatocarcinogenesis. This hypothesis is supported by previous observations of increased 8-oxo-deoxyguanosine (8-oxo-dG) adduct formation in the livers of intact, but not ovariectomized (OVX), rats following chronic exposure to TCDD. The aim of the current study was to more clearly define the roles of hormonal regulation, gender, dose-response, and exposure duration in TCDD induction of 8-oxo-dG adducts. Diethylnitrosamine (DEN)-intiated male and female (both intact and OVX) rats were exposed to TCDD in the presence or absence of 17 beta -estradiol. Following 30 weeks of exposure, hepatic 8-oxo-dG adduct levels were significantly higher in TCDD-treated intact female rats, and TCDD-treated OVX female rats receiving supplemental 17 beta -estradiol, when compared to respective corn oil vehicle controls. In DEN-initiated female rats exposed to a range of TCDD concentrations for 30 weeks, TCDD induced 8-oxo-dG adduct levels in a dose-dependent manner. However, 8-oxo-dG adduct levels were not altered in TCDD-treated male or OVX female rats following 30 weeks of exposure. In noninitiated female rats, the level of 8-oxo-dG adducts 4 days following a single dose of TCDD was not significantly different than in control rats. Additionally, 8-oxo-dG adduct formation was not affected by exposure to TCDD for 20 weeks in intact female rats. These data suggest that the induction of 8-oxo-dG adduct levels by TCDD is likely a response to chronic oxidative imbalance. These studies provide strong evidence that the induction of 8-oxo-dG by TCDD occurs via a chronic, sex-specific, estrogen-dependent mechanism. JF - Chemical Research in Toxicology AU - Wyde, ME AU - Wong, V A AU - Kim, AH AU - Lucier, G W AU - Walker, N J AD - National Institute of Environmental Health Sciences, Environmental Toxicology Program, Research Triangle Park, North Carolina 27709, USA Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 849 EP - 855 VL - 14 IS - 7 SN - 0893-228X, 0893-228X KW - rats KW - dose-response effects KW - 8-oxo-deoxyguanosine KW - Toxicology Abstracts KW - DNA adducts KW - Estrogens KW - Liver KW - TCDD KW - Sex differences KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18211709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Induction+of+Hepatic+8-Oxo-deoxyguanosine+Adducts+by+2%2C3%2C7%2C8-Tetrachlorodibenzo-p-dioxin+in+Sprague-Dawley+Rats+Is+Female-Specific+and+Estrogen-Dependent&rft.au=Wyde%2C+ME%3BWong%2C+V+A%3BKim%2C+AH%3BLucier%2C+G+W%3BWalker%2C+N+J&rft.aulast=Wyde&rft.aufirst=ME&rft.date=2001-07-01&rft.volume=14&rft.issue=7&rft.spage=849&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Estrogens; DNA adducts; TCDD; Liver; Sex differences ER - TY - JOUR T1 - Disruption of pituitary-ovarian axis by carbofuran in catfish, Heteropneustes fossilis (Bloch) AN - 18200527; 5221399 AB - We investigated whether carbofuran (CF), a carbamate pesticide, at sub-lethal concentration had any adverse effects on reproductive function of the Indian catfish, Heteropneustes fossilis. 17 beta -Estradiol content of serum and ovary of pre-spawning (P) and spawning (S) fish was reduced after sub-lethal concentration of carbofuran treatment (0.5-2 mg/ml, 30 days). After 30 days of CF treatment, the serum and ovarian vitellogenin levels of fish at the P stage were also reduced but remained unaltered in the S stage. The staining intensity of the pituitary gonadotrophs of the pre-spawning fish was significantly higher in CF-treated fish compared to controls suggesting the inability of the pituitary gonadotrophs to release gonadotropin following CF treatment. CF thus acts as an antiestrogenic, endocrine-disrupting agent in fish, possibly targeting the pituitary-gonad axis. JF - Comparative Biochemistry and Physiology, C AU - Chatterjee, S AU - Dasmahapatra, A K AU - Ghosh, R AD - NIEHS Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee, 600 East Greenfield Avenue, Milwaukee, WI 53204, USA, asok@uwm.edu Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 265 EP - 273 VL - 129 IS - 3 SN - 1532-0456, 1532-0456 KW - Stinging catfish KW - Toxicology Abstracts; ASFA 1: Biological Sciences & Living Resources; ASFA Aquaculture Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality KW - Heteropneustes fossilis KW - Carbofuran KW - Pituitary KW - Fish physiology KW - Pesticides KW - Pollution effects KW - Reproduction KW - Ovaries KW - Pesticides (carbamates) KW - Freshwater fish KW - Q5 08504:Effects on organisms KW - X 24132:Chronic exposure KW - Q3 08582:Fish culture KW - Q1 08344:Reproduction and development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18200527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comparative+Biochemistry+and+Physiology%2C+C&rft.atitle=Disruption+of+pituitary-ovarian+axis+by+carbofuran+in+catfish%2C+Heteropneustes+fossilis+%28Bloch%29&rft.au=Chatterjee%2C+S%3BDasmahapatra%2C+A+K%3BGhosh%2C+R&rft.aulast=Chatterjee&rft.aufirst=S&rft.date=2001-07-01&rft.volume=129&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Comparative+Biochemistry+and+Physiology%2C+C&rft.issn=15320456&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Fish physiology; Pesticides; Pollution effects; Reproduction; Freshwater fish; Carbofuran; Pituitary; Ovaries; Pesticides (carbamates); Heteropneustes fossilis ER - TY - JOUR T1 - Development of human anti-thymidine kinase antibodies AN - 18177682; 5175136 AB - Thymidine kinase (TK) is a key enzyme involved in the nucleotide salvage pathway leading to the intracellular synthesis of thymidylate through the phosphorylation of preformed thymidine nucleosides. It has previously been shown that cellular TK levels are regulated by intracellular levels of dTTP. A recent study from our laboratory has shown that exposure to camptothecin analogs, such as 9-aminocamptothecin, results in the inhibition of TK through an indirect mechanism not associated with changes in intracellular dTTP pools. To enable further investigation of this inhibitory mechanism and to provide a reagent useful for other investigations of TK, we have developed anti-TK antibodies in rabbits using peptides of TK. TK is an important determinant of cellular sensitivity to fluoropyrimidines and to several new antifolate inhibitors of thymidylate synthase. Thus, the availability of antibodies against TK would facilitate investigations of the role of this enzyme as a potential predictor of responsiveness to these commonly used chemotherapeutic agents. JF - Anti-Cancer Drugs AU - Voeller, D M AU - Parr, A AU - Allegra, C J AD - National Naval Medical Center, 8901 Wisconsin Avenue, Building 8, Room 5101, Bethesda, MD 20889, USA, voellerd@navmed.nci.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 555 EP - 559 VL - 12 IS - 6 SN - 0959-4973, 0959-4973 KW - man KW - 9-aminocamptothecin KW - nucleosides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Antibodies KW - Chemotherapy KW - Thymidine kinase KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18177682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-Cancer+Drugs&rft.atitle=Development+of+human+anti-thymidine+kinase+antibodies&rft.au=Voeller%2C+D+M%3BParr%2C+A%3BAllegra%2C+C+J&rft.aulast=Voeller&rft.aufirst=D&rft.date=2001-07-01&rft.volume=12&rft.issue=6&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Anti-Cancer+Drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antibodies; Thymidine kinase; Chemotherapy ER - TY - JOUR T1 - Occupation and leukemia: A population-based case - control study in Iowa and Minnesota AN - 18170283; 5166625 AB - Background: Studies have suggested that risk of leukemia may be associated with occupational or industrial exposures and risk may vary by the histological type of the disease. Methods: A population-based case - control study was conducted in Iowa and Minnesota to evaluate the association between various occupations, industries, and occupational exposures and leukemia risk. A total of 513 cases and 1,087 controls was included in the study. A lifetime occupational history and other risk factor information were collected through in-person interviews, and a job-exposure matrix was used to assess possible risks associated with specific exposures. Results: A significantly increased risk of leukemia was observed among agricultural service industries and among nursing and healthcare workers. Janitors, cleaners, and light truck drivers also experienced increased risk. Those employed in plumbing, heating and air conditioning industries, and sales of nondurable goods (such as paints and varnishes) had an increased risk. Printers, painters, and workers in the food and metal industries had a nonsignificantly increased risk of leukemia. Analyses by specific exposures and histology of leukemia showed that risk of leukemia associated with occupational or industrial exposures may vary by histological type of the disease. Conclusions: An increased risk of leukemia among workers employed in agricultural industries, nursing and healthcare workers, and in a few occupations with possible exposure to solvents is consistent with earlier studies. Associations of risk with occupations not observed previously deserve further assessment. JF - American Journal of Industrial Medicine AU - Blair, A AU - Zheng, T AU - Linos, A AU - Stewart, P A AU - Zhang, Y W AU - Cantor, K P AD - Occupational Epidemiology Branch, The National Cancer Institute, 6120 Executive Blvd. EPS 8118, MSC 7240, Bethesda, MD 20892, USA, blaira@mail.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 3 EP - 14 VL - 40 IS - 1 SN - 0271-3586, 0271-3586 KW - man KW - USA, Iowa KW - USA, Minnesota KW - Risk Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Agriculture KW - Leukemogenesis KW - Medical personnel KW - Leukemia KW - Agricultural practices KW - Nursing KW - Occupational exposure KW - Solvents KW - R2 23080:Industrial and labor KW - X 24240:Miscellaneous KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18170283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Occupation+and+leukemia%3A+A+population-based+case+-+control+study+in+Iowa+and+Minnesota&rft.au=Blair%2C+A%3BZheng%2C+T%3BLinos%2C+A%3BStewart%2C+P+A%3BZhang%2C+Y+W%3BCantor%2C+K+P&rft.aulast=Blair&rft.aufirst=A&rft.date=2001-07-01&rft.volume=40&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, Iowa; USA, Minnesota; Occupational exposure; Leukemia; Medical personnel; Agriculture; Solvents; Leukemogenesis; Risk assessment; Agricultural practices; Nursing ER - TY - JOUR T1 - Race and Sex Effects on the Association Between Muscle Strength, Soft Tissue, and Bone Mineral Density in Healthy Elders: The Health, Aging, and Body Composition Study AN - 18145342; 5162412 AB - Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm super(2)) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both FM and muscle strength contributed to limb BMD. The following were the respective beta -weights (regression coefficients for standardized data, Std beta ) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-5.9%; lower limb, 0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7%; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex. JF - Journal of Bone and Mineral Research AU - Taaffe AU - Cauley, JA AU - Danielson, M AU - Nevitt, M C AU - Lang, T F AU - Bauer, D C AU - Harris, T B AD - Epidemiology, Demography and Biometry Program, National Institute on Aging, Bethesda, MD, USA Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 1343 EP - 1352 VL - 16 IS - 7 SN - 0884-0431, 0884-0431 KW - man KW - Physical Education Index; Calcium & Calcified Tissue Abstracts KW - Bones KW - Health (status) KW - Gerontology KW - Race differences KW - Sex differences KW - Sexual behavior KW - Age differences KW - Strength (measurement) KW - Bone mineral density KW - Geriatrics KW - Body composition KW - Ethnic groups KW - PE 090:Sports Medicine & Exercise Sport Science KW - T 20004:Aging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18145342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bone+and+Mineral+Research&rft.atitle=Race+and+Sex+Effects+on+the+Association+Between+Muscle+Strength%2C+Soft+Tissue%2C+and+Bone+Mineral+Density+in+Healthy+Elders%3A+The+Health%2C+Aging%2C+and+Body+Composition+Study&rft.au=Taaffe%3BCauley%2C+JA%3BDanielson%2C+M%3BNevitt%2C+M+C%3BLang%2C+T+F%3BBauer%2C+D+C%3BHarris%2C+T+B&rft.aulast=Taaffe&rft.aufirst=&rft.date=2001-07-01&rft.volume=16&rft.issue=7&rft.spage=1343&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bone+and+Mineral+Research&rft.issn=08840431&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bones; Ethnic groups; Sexual behavior; Health (status); Gerontology; Body composition; Strength (measurement); Geriatrics; Race differences; Sex differences; Bone mineral density; Age differences ER - TY - JOUR T1 - Hydroxychloroquine Enhances the Endocrine Secretion of Adenovirus-Directed Growth Hormone from Rat Submandibular Glands In Vivo AN - 18077955; 5161007 AB - Use of gene transfer technology for treating single protein deficiency disorders requires delivery of therapeutic levels of the transgene product. We have suggested that salivary glands may provide a potentially valuable target site for certain systemic applications of gene therapeutics. However, the ability of salivary glands to deliver therapeutic proteins to either the upper gastrointestinal tract via saliva or to the bloodstream, as required, must be carefully evaluated. In the anterior pituitary gland, human growth hormone (hGH) is secreted into the bloodstream via the regulated secretory pathway. However, when expressed from an adenoviral vector delivered to salivary glands, most hGH follows the regulated, tissue-specific, exocrine secretory pathway into saliva, where it is not therapeutically useful. We tested the hypothesis that the commonly used, FDA-approved drug hydroxychloroquine (HCQ) can divert adenovirus-directed hGH from this regulated secretory pathway in rat submandibular glands and enhance delivery into the bloodstream. In untreated rats, there was similar to 20-fold more vector-directed hGH in saliva than in serum. Administration of HCQ led to a shift of hGH secretion into the bloodstream. When delivered at doses of 1 or 10 mg/kg body weight, via intraperitoneal injection plus intraductal infusion, the saliva:serum hGH ratio was similar to 2:1. Such HCQ delivery did not significantly alter the total amount of hGH measured, but increased the serum level of hGH 5- to 6-fold. Also, HCQ had no significant effects on serum chemistries or hematological parameters. We conclude that HCQ is able to significantly enhance hGH secretion from salivary glands into the bloodstream and may be useful to facilitate clinical applications of gene therapeutics via salivary glands. JF - Human Gene Therapy AU - Hoque, ATMS AU - Baccaglini, L AU - Baum, B J AD - GTTB, NIDCR, NIH, Building 10, Room 1N113, MSC-1190, Bethesda, MD 20892-1190, USA, bbaum@dir.nidcr.nih.gov Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 1333 EP - 1341 VL - 12 IS - 10 SN - 1043-0342, 1043-0342 KW - rats KW - man KW - growth hormone KW - hydroxychloroquine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Gene transfer KW - Adenovirus KW - Submandibular gland KW - Endocrine system KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18077955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Hydroxychloroquine+Enhances+the+Endocrine+Secretion+of+Adenovirus-Directed+Growth+Hormone+from+Rat+Submandibular+Glands+In+Vivo&rft.au=Hoque%2C+ATMS%3BBaccaglini%2C+L%3BBaum%2C+B+J&rft.aulast=Hoque&rft.aufirst=ATMS&rft.date=2001-07-01&rft.volume=12&rft.issue=10&rft.spage=1333&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Endocrine system; Submandibular gland; Gene therapy; Gene transfer ER - TY - JOUR T1 - Three-Dimensional Structures of Protein-Protein Complexes in the E. coli PTS AN - 18077502; 5133349 AB - The bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) includes a collection of proteins that accomplish phosphoryl transfer from phosphoenolpyruvate (PEP) to a sugar in the course of transport. The soluble proteins of the glucose transport pathway also function as regulators of diverse systems. The mechanism of interaction of the phosphoryl carrier proteins with each other as well as with their regulation targets has been amenable to study by nuclear magnetic resonance (NMR) spectroscopy. The three-dimensional solution structures of the complexes between the N-terminal domain of enzyme I and HPr and between HPr and enzyme IIA super(Glc) have been elucidated. An analysis of the binding interfaces of HPr with enzyme I, IIA super(Glc) and glycogen phosphorylase revealed that a common surface on HPr is involved in all these interactions. Similarly, a common surface on IIA super(Glc) interacts with HPr, IIB super(Glc) and glycerol kinase. Thus, there is a common motif for the protein-protein interactions characteristic of the PTS. JF - Journal of Molecular Microbiology and Biotechnology AU - Peterkofsky, A AU - Wang, Guangshun AU - Garrett, D S AU - Lee, B R AU - Seok, Yeong-Jae AU - Clore, G M AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg. 36, Rm. 4C-11, Bethesda, MD 20892-4036, USA, alan@codon.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 347 EP - 354 VL - 3 IS - 3 SN - 1464-1801, 1464-1801 KW - phosphoenolpyruvic acid KW - phosphoryl carrier proteins KW - phosphotransferase KW - proteins KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Tertiary structure KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18077502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.atitle=Three-Dimensional+Structures+of+Protein-Protein+Complexes+in+the+E.+coli+PTS&rft.au=Peterkofsky%2C+A%3BWang%2C+Guangshun%3BGarrett%2C+D+S%3BLee%2C+B+R%3BSeok%2C+Yeong-Jae%3BClore%2C+G+M&rft.aulast=Peterkofsky&rft.aufirst=A&rft.date=2001-07-01&rft.volume=3&rft.issue=3&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Tertiary structure ER - TY - JOUR T1 - Lack of usefulness of carbon utilization tests for identification of Mycobacterium mucogenicum AN - 17923678; 5165087 AB - Carbon utilization tests have proven to be useful for the identification of some species of rapidly growing mycobacteria and have been described as one of the few tests useful for the differentiation of Mycobacterium mucogenicum from other rapid growers. We have found the carbon utilization tests to be unreliable for the identification of patient isolates of this species. In this study, using 28 isolates of rapidly growing mycobacteria, we examined several variables which might have an effect on results of citrate, inositol, and mannitol utilization: inoculum concentration, incubation temperature, and medium manufacturer. None of these variables affected results obtained for most species of rapid growers or for ATCC strains of M. mucogenicum. Results for patient isolates of M. mucogenicum were found to be inconsistent regardless of the methodology employed and resulted in an ambiguous identification of these isolates or an incorrect identification as Mycobacterium chelonae. Molecular or cell wall analysis may be the best technique to employ for accurate identification of M. mucogenicum. JF - Journal of Clinical Microbiology AU - Conville, P S AU - Witebsky, F G AD - Microbioiogy Service, Department of Laboratory Medicine, National Institutes of Health, 10 Center Dr. MSC 1508, Bethesda, MD 20892- 1508, USA, pconville@nih.gov. Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 2725 EP - 2728 VL - 39 IS - 7 SN - 0095-1137, 0095-1137 KW - phenotyping KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Nutrient utilization KW - Concentration KW - Phenotyping KW - Mycobacterium mucogenicum KW - Carbon KW - Media (culture) KW - J 02710:Identification, taxonomy and typing KW - A 01116:Bacteria KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17923678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Lack+of+usefulness+of+carbon+utilization+tests+for+identification+of+Mycobacterium+mucogenicum&rft.au=Conville%2C+P+S%3BWitebsky%2C+F+G&rft.aulast=Conville&rft.aufirst=P&rft.date=2001-07-01&rft.volume=39&rft.issue=7&rft.spage=2725&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium mucogenicum; Phenotyping; Nutrient utilization; Concentration; Temperature effects; Media (culture); Carbon ER - TY - JOUR T1 - Modulation of Mouse P450 Isoforms CYP1A2, CYP2B10, CYP2E1, and CYP3A by the Environmental Chemicals Mirex, 2,2-Bis(p-chlorophenyl)-1,1-dichloroethylene, Vinclozolin, and Flutamide AN - 17919323; 5158203 AB - Several environmental chemicals are disruptive to the reproductive and endocrine systems of many species, including humans. Mechanisms for endocrine disruption are presently under scrutiny. Xenobiotic inducible mammalian cytochrome P450 (CYP) enzymes metabolize a variety of substrates including environmental chemicals, pesticides, and drugs. The metabolism, and thus the effect, of endogenous chemicals including steroid hormones, vitamins, etc. that are transformed by CYP enzymes can be influenced by environmental exposure to CYP-inducing chemicals. This study demonstrated that structurally diverse environmental chemicals including mirex, 2,2-Bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), vinclozolin, and flutamide are capable of inducing several mouse liver CYP isozymes. As demonstrated by Western blotting, mirex induced CYP1A2, 2B10, 2E1, and 3A and vinclozolin induced 1A2 and 2B10. The only isoforms significantly induced by DDE and flutamide were 3A and 1A2, respectively. Since some of these isoforms are known to be involved in metabolism of endogenous hormones, we also studied the effects of these CYP inducers on testosterone metabolism and seminal vesicle weights. Mirex and DDE treatments had profound effects on the metabolism of testosterone, resulting in 2.5- to 3-fold more hydroxylated products than controls. Lesser, but significant, increases in specific metabolites of testosterone were also observed following treatment with vinclozolin and flutamide. Seminal vesicle weights were lower for all treatment groups except DDE. Results of this study demonstrate that, due to their CYP-inducing potential, these chemicals may significantly impact testosterone metabolism and this may be a contributing factor in their antiandrogenic effects. Copyright 2001 Academic Press. JF - Pesticide Biochemistry and Physiology AU - Dai, D AU - Cao, Y AU - Falls, G AU - Levi, P E AU - Hodgson, E AU - Rose, R L AD - NIEHS, Research Triangle Park, North Carolina, 27709, randy_rose@ncsu.edu Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 127 EP - 141 PB - Academic Press VL - 70 IS - 3 SN - 0048-3575, 0048-3575 KW - mice KW - mirex KW - Toxicology Abstracts KW - Western blotting KW - Testosterone KW - Vinclozolin KW - Isoforms KW - DDE KW - Cytochrome P450 KW - Flutamide KW - Androgens KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17919323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pesticide+Biochemistry+and+Physiology&rft.atitle=Modulation+of+Mouse+P450+Isoforms+CYP1A2%2C+CYP2B10%2C+CYP2E1%2C+and+CYP3A+by+the+Environmental+Chemicals+Mirex%2C+2%2C2-Bis%28p-chlorophenyl%29-1%2C1-dichloroethylene%2C+Vinclozolin%2C+and+Flutamide&rft.au=Dai%2C+D%3BCao%2C+Y%3BFalls%2C+G%3BLevi%2C+P+E%3BHodgson%2C+E%3BRose%2C+R+L&rft.aulast=Dai&rft.aufirst=D&rft.date=2001-07-01&rft.volume=70&rft.issue=3&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Pesticide+Biochemistry+and+Physiology&rft.issn=00483575&rft_id=info:doi/10.1006%2Fpest.2001.2551 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Isoforms; Testosterone; Androgens; DDE; Western blotting; Cytochrome P450; Vinclozolin; Flutamide DO - http://dx.doi.org/10.1006/pest.2001.2551 ER - TY - JOUR T1 - Expression of Genes Encoding Th1 Cell-Activating Cytokines and Lymphoid Homing Chemokines by Chlamydia-Pulsed Dendritic Cells Correlates with Protective Immunizing Efficacy AN - 17895980; 5135300 AB - We studied the expression of cytokines, chemokines, and chemokine receptors by the RNase protection assay in chlamydia-pulsed dendritic cells to better understand their potent anti-chlamydial immunizing properties. We found that chlamydia-pulsed dendritic cells express a complex profile of inflammatory and immunomodulatory molecules. These include CCR-7, interleukin-12, and interferon-induced protein 10, molecules that might influence the homing of pulsed dendritic cells to the site of chlamydial infection and the induction of a local protective CD4 super(+) Th1 cellular immunity. JF - Infection and Immunity AU - Shaw, J H AU - Grund, V R AU - Durling, L AU - Caldwell, H D AD - Laboratory of Intercellular Parasites, National Institute of Allergy and Infectious Diseases, NIH Rocky Mountain Laboratory, 903 South 4th St., Hamilton, MT 59840, hcaldwell@niaid.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 4667 EP - 4672 VL - 69 IS - 7 SN - 0019-9567, 0019-9567 KW - CCR7 protein KW - Chlamydia KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Chemokines KW - Helper cells KW - Chemokine receptors KW - Interleukin 12 KW - Dendritic cells KW - Immune response (cell-mediated) KW - Lymphocytes T KW - Vaccines KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Expression+of+Genes+Encoding+Th1+Cell-Activating+Cytokines+and+Lymphoid+Homing+Chemokines+by+Chlamydia-Pulsed+Dendritic+Cells+Correlates+with+Protective+Immunizing+Efficacy&rft.au=Shaw%2C+J+H%3BGrund%2C+V+R%3BDurling%2C+L%3BCaldwell%2C+H+D&rft.aulast=Shaw&rft.aufirst=J&rft.date=2001-07-01&rft.volume=69&rft.issue=7&rft.spage=4667&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.7.4667-4672.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia; Lymphocytes T; Helper cells; Dendritic cells; Interleukin 12; Immune response (cell-mediated); Vaccines; Chemokines; Chemokine receptors DO - http://dx.doi.org/10.1128/IAI.69.7.4667-4672.2001 ER - TY - JOUR T1 - Signal Transduction Cascade for Regulation of RpoS: Temperature Regulation of DsrA AN - 17895588; 5139581 AB - Many environmental parameters modulate the amount of the RpoS sigma factor in Escherichia coli. Temperature control of RpoS depends on the untranslated RNA DsrA. DsrA activates RpoS translation by pairing with the leader of the mRNA. We find that temperature affects both the rate of transcription initiation of the dsrA gene and the stability of DsrA RNA. Both are increased at low temperature (25 degree C) compared to 37 or 42 degree C. The combination of these results is 25-fold-less DsrA at 37 degree C and 30- fold less at 42 degree C than at 25 degree C. Using an adapted lacZ-based reporter system, we show that temperature control of transcription initiation of dsrA requires only the minimal promoter of 36 bp. Overall, transcription responses to temperature lead to a sixfold increase in DsrA synthesis at 25 degree C over that at 42 degree C. Furthermore, two activating regions and a site for LeuO negative regulation were identified in the dsrA promoter. The activating regions also activate transcription in vitro. DsrA decays with a half-life of 23 min at 25 degree C and 4min at 37 and 42 degree C. These results demonstrate that the dsrA promoter and the stability of DsrA RNA are the thermometers for RpoS temperature sensing. Multiple inputs to DsrA accumulation allow sensitive modulation of changes in the synthesis of the downstream targets of DsrA such as RpoS. JF - Journal of Bacteriology AU - Repoila, F AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Dr., Bldg. 37, Room 2E18, National Institutes of Health, Bethesda, MD 20892-4255, susang@helix.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 4012 EP - 4023 VL - 183 IS - 13 SN - 0021-9193, 0021-9193 KW - RpoS protein KW - dsrA gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - DNA-directed RNA polymerase KW - Escherichia coli KW - Sigma factor KW - Transcription initiation KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Signal+Transduction+Cascade+for+Regulation+of+RpoS%3A+Temperature+Regulation+of+DsrA&rft.au=Repoila%2C+F%3BGottesman%2C+S&rft.aulast=Repoila&rft.aufirst=F&rft.date=2001-07-01&rft.volume=183&rft.issue=13&rft.spage=4012&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.183.13.4012-4023.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Transcription initiation; DNA-directed RNA polymerase; Sigma factor; Temperature effects DO - http://dx.doi.org/10.1128/JB.183.13.4012-4023.2001 ER - TY - JOUR T1 - Helicobacter hepaticus-Induced Colitis in Interleukin-10-Deficient Mice: Cytokine Requirements for the Induction and Maintenance of Intestinal Inflammation AN - 17889572; 5135273 AB - We have previously shown that specific-pathogen-free interleukin-10 (IL-10)-deficient (IL-10 KO) mice reconstituted with Helicobacter hepaticus develop severe colitis associated with a Th1-type cytokine response. In the present study, we formally demonstrate that IL-12 is crucial for disease induction, because mice deficient for both IL-10 and IL-12 p40 show no intestinal pathology following H. hepaticus infection. By using monoclonal antibodies (MAbs) to IL-12, gamma interferon (IFN- gamma ), and tumor necrosis factor alpha (TNF- alpha ), we have further analyzed the role of these cytokines in the maintenance of the Th1 response and inflammation in IL-10 KO mice with established H. hepaticus-induced colitis. Treatment of infected colitic IL-10 KO mice with anti-IL- 12 p40 resulted in markedly reduced intestinal inflammation, colonic IFN- gamma , TNF- alpha , and inducible nitric oxide synthase (iNOS) mRNA levels, and H. hepaticus-specific IFN- gamma secretion by mesenteric lymph node (MLN) cells compared to the findings in control MAb-treated mice. Moreover, the diminished pathology was associated with decreased numbers of colonic CD3 super(+) T cells and significantly reduced frequencies of Helicobacter-reactive CD4 super(+) Th1 cells in MLN. In contrast, anti-IFN- gamma and/or anti-TNF- alpha had no effect on intestinal inflammation in IL-10 KO mice with established colitis. Using IL-10/IFN- gamma double-deficient mice, we further show that IFN- gamma is not required for the development of colitis follwing H. hepaticus infection. MLN cells from infected IL-10/IFN- gamma KO animals secreted elevated amounts of IL-12 and TNF- alpha following bacterial antigen stimulation, indicating alternative pathways of disease induction. Taken together, our results demonstrate a crucial role for IL-12 in both inducing and sustaining intestinal inflammation through recruitment and maintenance of a pool of pathogenic Th1 cells. JF - Infection and Immunity AU - Kullberg, M C AU - Rothfuchs, A G AU - Jankovic, D AU - Caspar, P AU - Wynn, T A AU - Gorelick, P L AU - Cheever, A W AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, 4 Center Dr., Bethesda, MD 20892-0425, mkullberg@niaid.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 4232 EP - 4241 VL - 69 IS - 7 SN - 0019-9567, 0019-9567 KW - mice KW - Helicobacter hepaticus KW - gamma -Interferon KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - ^g-Interferon KW - Tumor necrosis factor-a KW - Interleukin 10 KW - Inflammation KW - Nitric-oxide synthase KW - Tumor necrosis factor-^a KW - Intestine KW - Cytokines KW - Colitis KW - F 06774:Other cytokines (TNF, GM-CSF) KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17889572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Helicobacter+hepaticus-Induced+Colitis+in+Interleukin-10-Deficient+Mice%3A+Cytokine+Requirements+for+the+Induction+and+Maintenance+of+Intestinal+Inflammation&rft.au=Kullberg%2C+M+C%3BRothfuchs%2C+A+G%3BJankovic%2C+D%3BCaspar%2C+P%3BWynn%2C+T+A%3BGorelick%2C+P+L%3BCheever%2C+A+W%3BSher%2C+A&rft.aulast=Kullberg&rft.aufirst=M&rft.date=2001-07-01&rft.volume=69&rft.issue=7&rft.spage=4232&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.7.4232-4241.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter hepaticus; Interleukin 10; Cytokines; Colitis; Intestine; Inflammation; Tumor necrosis factor-a; Nitric-oxide synthase; Tumor necrosis factor-^a DO - http://dx.doi.org/10.1128/IAI.69.7.4232-4241.2001 ER - TY - JOUR T1 - The Y-Family of DNA Polymerases AN - 17889423; 5161764 AB - Based on phylogenetic relationships, DNA polymerases can be broadly classified into five families. The A-family is typified by Escherichia coli DNA polymerase I (pol I); the B-family by E. coli pol II; the C-family by the E. coli pol III alpha -catalytic subunit; the D-family by archeal polymerases; and the X-family by eukaryotic pol beta . Recently, a large number of new DNA polymerases have been identified, which although sharing significant amino acid sequence identity and similarity amongst themselves, exhibit little homology to any of the five previously identified polymerase families. This new family of polymerases has been described in the literature as the UmuC/DinB/Rev1/Rad30 superfamily. At the present time, these enzymes are best characterized in terms of their low-fidelity synthesis on undamaged DNA and their ability to bypass DNA lesions in vitro which normally block replication by members of the A-, B-, C-, D-, or X-family of polymerases. In keeping with the original suggestion of Ito and Braithwaite that related enzymes be identified by a distinct "family name"(Ito and Braithwaite, 1991), we formally propose that henceforth the UmuC/DinB/Rev1/Rad30 DNA polymerases be referred to as the "Y-family" of DNA polymerases. JF - Molecular Cell AU - Ohmori, H AU - Friedberg, E C AU - Fuchs, RPP AU - Goodman, M F AU - Hanaoka, F AU - Hinkle, D AU - Kunkel, T A AU - Lawrence, C W AU - Livneh, Z AU - Nohmi, T AU - Prakash, L AU - Prakash, S AU - Todo, T AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis National Institute of Child Health and Human Development Bethesda, Maryland 20892, USA, woodgate@helix.nih.gov Y1 - 2001/07// PY - 2001 DA - Jul 2001 SP - 7 EP - 8 VL - 8 IS - 1 SN - 1097-2765, 1097-2765 KW - Y-family KW - DinB protein KW - Rad30 protein KW - Rev1 protein KW - UmuC protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Phylogeny KW - DNA-directed DNA polymerase KW - Reviews KW - Escherichia coli KW - J 02725:DNA KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17889423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Cell&rft.atitle=The+Y-Family+of+DNA+Polymerases&rft.au=Ohmori%2C+H%3BFriedberg%2C+E+C%3BFuchs%2C+RPP%3BGoodman%2C+M+F%3BHanaoka%2C+F%3BHinkle%2C+D%3BKunkel%2C+T+A%3BLawrence%2C+C+W%3BLivneh%2C+Z%3BNohmi%2C+T%3BPrakash%2C+L%3BPrakash%2C+S%3BTodo%2C+T%3BWoodgate%2C+R&rft.aulast=Ohmori&rft.aufirst=H&rft.date=2001-07-01&rft.volume=8&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Molecular+Cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Reviews; Phylogeny; DNA-directed DNA polymerase ER - TY - JOUR T1 - Pertussis Toxin Inhibits Induction of Tissue-Specific Autoimmune Disease by Disrupting G Protein-Coupled Signals AN - 17887621; 5135179 AB - Pertussis toxin (PTX) has been used for many years as an adjuvant that promotes development of tissue-specific experimental autoimmune diseases such as experimental autoimmune encephalomyelitis, experimental autoimmune uveitis (EAU), and others. Enhancement of vascular permeability and of Th1 responses have been implicated in this effect. Here we report a surprising observation that, in a primed system, PTX can completely block the development of EAU. Disease was induced in B10.RIII mice by adoptive transfer of uveitogenic T cells, or by immunization with a uveitogenic peptide. A single injection of PTX concurrently with infusion of the uveitogenic T cells, or two injections 7 and 10 days after active immunization, completely blocked development of EAU. EAU also was prevented by a 1-h incubation in vitro of the uveitogenic T cells with PTX before infusing them into recipients. Uveitogenic T cells treated with PTX in vitro and lymphoid cells from mice treated with PTX in vivo failed to migrate to chemokines in a standard chemotaxis assay. Neither the isolated B-oligomer subunit of PTX that lacks ADP ribosyltransferase activity nor the related cholera toxin that ADP-ribosylates G sub(s) (but not G sub(i)) proteins blocked EAU induction or migration to chemokines. We conclude that PTX present at the time of cell migration to the target organ prevents EAU, and propose that it does so at least in part by disrupting signaling through G sub(i) protein-coupled receptors. Thus, the net effect of PTX on autoimmune disease would represent an integration of enhancing and inhibitory effects. JF - Journal of Immunology AU - Su, S B AU - Silver, P B AU - Zhang, M AU - Chan, C AU - Caspi, R R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892 Y1 - 2001/07/01/ PY - 2001 DA - 2001 Jul 01 SP - 250 EP - 256 VL - 167 IS - 1 SN - 0022-1767, 0022-1767 KW - mice KW - experimental autoimmune uveitis KW - pertussis toxin KW - Immunology Abstracts; Toxicology Abstracts KW - Bordetella pertussis KW - G protein-coupled receptors KW - Autoimmune diseases KW - Adoptive transfer KW - ^AG protein-coupled receptors KW - Adjuvants KW - X 24171:Microbial KW - F 06873:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17887621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Pertussis+Toxin+Inhibits+Induction+of+Tissue-Specific+Autoimmune+Disease+by+Disrupting+G+Protein-Coupled+Signals&rft.au=Su%2C+S+B%3BSilver%2C+P+B%3BZhang%2C+M%3BChan%2C+C%3BCaspi%2C+R+R&rft.aulast=Su&rft.aufirst=S&rft.date=2001-07-01&rft.volume=167&rft.issue=1&rft.spage=250&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bordetella pertussis; G protein-coupled receptors; Adoptive transfer; Autoimmune diseases; Adjuvants; ^AG protein-coupled receptors ER - TY - JOUR T1 - cAMP Regulation of Arylalkylamine N-Acetyltransferase (AANAT, EC 2.3.1.87): A new cell line (1E7) provides evidence of intracellular AANAT activation AN - 18182837; 5135950 AB - Arylalkylamine N-acetyltransferase (serotonin N-acetyltransferase, AANAT, EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis. As described here, a cell line (1E7) expressing human AANAT (hAANAT) has been developed to study the human enzyme. 1E7 hAANAT is detectable in immunoblots as a 23-kDa band and is immunocytochemically visualized in the cytoplasm. The specific concentration of hAANAT in homogenates is comparable to that of the night rat pineal gland. Kinetics of AANAT extracted from 1E7 cells are the same as those of bacterially expressed hAANAT; both preparations of hAANAT are equally sensitive to the inhibitor CoA-S-N-acetyltryptamine. Studies of cAMP regulation indicate that treatment with forskolin, dibutyryl cAMP, isobutylmethylxanthine, or isoproterenol activate cellular hAANAT within intact 1E7 cells similar to 8-fold without markedly increasing the abundance of AANAT protein or the activity of AANAT in broken cell preparations; and, that forskolin, isobutylmethylxanthine and isoproterenol elevate cyclic AMP production. These observations extend our understanding of cAMP regulation of AANAT activity, because it is currently thought that this only involves changes in the steady-state levels of AANAT protein. This previously unrecognized switching mechanism could function physiologically to control melatonin production without changing AANAT protein levels. JF - Journal of Biological Chemistry AU - Coon, S L AU - Weller, J L AU - Korf, H W AU - Namboodiri, MAA AU - Rollag, M AU - Klein, D C AD - Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA, klein@helix.nih.gov Y1 - 2001/06/29/ PY - 2001 DA - 2001 Jun 29 SP - 24097 EP - 24107 VL - 276 IS - 26 SN - 0021-9258, 0021-9258 KW - man KW - cyclic AMP KW - dibutyryl cyclic AMP KW - forskolin KW - isobutylmethylxanthine KW - isoproterenol KW - melatonin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Aralkylamine N-acetyltransferase KW - W3 33310:Enzymes and cofactors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18182837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=cAMP+Regulation+of+Arylalkylamine+N-Acetyltransferase+%28AANAT%2C+EC+2.3.1.87%29%3A+A+new+cell+line+%281E7%29+provides+evidence+of+intracellular+AANAT+activation&rft.au=Coon%2C+S+L%3BWeller%2C+J+L%3BKorf%2C+H+W%3BNamboodiri%2C+MAA%3BRollag%2C+M%3BKlein%2C+D+C&rft.aulast=Coon&rft.aufirst=S&rft.date=2001-06-29&rft.volume=276&rft.issue=26&rft.spage=24097&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aralkylamine N-acetyltransferase ER - TY - JOUR T1 - DnaA Boxes in the P1 Plasmid Origin: The Effect of Their Position on the Directionality of Replication and Plasmid Copy Number AN - 17913488; 5145446 AB - The DnaA protein is essential for initiation of DNA replication in a wide variety of bacterial and plasmid replicons. The replication origin in these replicons invariably contains specific binding sites for the protein, called DnaA boxes. Plasmid P1 contains a set of DnaA boxes at each end of its origin but can function with either one of the sets. Here we report that the location of origin-opening, initiation site of replication forks and directionality of replication do not change whether the boxes are present at both or at one of the ends of the origin. Replication was bidirectional in all cases. These results imply that DnaA functions similarly from the two ends of the origin. However, origins with DnaA boxes proximal to the origin-opening location opened more efficiently and maintained plasmids at higher copy numbers. Origins with the distal set were inactive unless the adjacent P1 DNA sequences beyond the boxes were included. At either end, phasing of the boxes with respect to the remainder of the origin influenced the copy number. Thus, although the boxes can be at either end, their precise context is critical for efficient origin function. Copyright 2001 Academic Press JF - Journal of Molecular Biology AU - Park, K AU - Chattoraj, D K AD - Laboratory of Biochemistry, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-4255, USA Y1 - 2001/06/29/ PY - 2001 DA - 2001 Jun 29 SP - 69 EP - 81 PB - Academic Press VL - 310 IS - 1 SN - 0022-2836, 0022-2836 KW - DnaA box KW - DnaA protein KW - copy number KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Replication KW - Plasmids KW - J 02760:Plasmids KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17913488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=DnaA+Boxes+in+the+P1+Plasmid+Origin%3A+The+Effect+of+Their+Position+on+the+Directionality+of+Replication+and+Plasmid+Copy+Number&rft.au=Park%2C+K%3BChattoraj%2C+D+K&rft.aulast=Park&rft.aufirst=K&rft.date=2001-06-29&rft.volume=310&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2001.4741 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmids; Replication DO - http://dx.doi.org/10.1006/jmbi.2001.4741 ER - TY - JOUR T1 - Differential Incorporation and Removal of Antiviral Deoxynucleotides by Human DNA Polymerase gamma AN - 17895454; 5135883 AB - Mitochondrial toxicity can result from antiviral nucleotide analog therapy used to control human immunodeficiency virus type 1 infection. We evaluated the ability of such analogs to inhibit DNA synthesis by the human mitochondrial DNA polymerase (pol gamma ) by comparing the insertion and exonucleolytic removal of six antiviral nucleotide analogs. Apparent steady-state K sub(m) and k sub(cat) values for insertion of 2',3'-dideoxy-TTP (ddTTP), 3'-azido-TTP (AZT-TP), 2',3'-dideoxy-CTP (ddCTP), 2',3'-didehydro-TTP (D4T-TP), (-)-2',3'- dideoxy-3'- thiacytidine (3TC-TP), and carbocyclic 2',3'-didehydro-ddGTP (CBV-TP) indicated incorporation of all six analogs, albeit with varying efficiencies. Dideoxynucleotides and D4T-TP were utilized by pol gamma in vitro as efficiently as natural deoxynucleotides, whereas AZT-TP, 3TC-TP, and CBV-TP were only moderate inhibitors of DNA chain elongation. Inefficient excision of dideoxynucleotides, D4T, AZT, and CBV from DNA predicts persistence in vivo following successful incorporation. In contrast, removal of 3'-terminal 3TC residues was 50% as efficient as natural 3' termini. Finally, we observed inhibition of exonuclease activity by concentrations of AZT-monophosphate known to occur in cells. Thus, although their greatest inhibitory effects are through incorporation and chain termination, persistence of these analogs in DNA and inhibition of exonucleolytic proofreading may also contribute to mitochondrial toxicity. JF - Journal of Biological Chemistry AU - Lim, SE AU - Copeland, W C AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA, copelan1@niehs.nih.gov Y1 - 2001/06/29/ PY - 2001 DA - 2001 Jun 29 SP - 23616 EP - 23623 VL - 276 IS - 26 SN - 0021-9258, 0021-9258 KW - man KW - analogues KW - antiviral nucleotide analog therapy KW - HIV KW - exonuclease KW - nucleotide analogues KW - nucleotides KW - pol gamma KW - Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Toxicology Abstracts KW - pol ^g KW - DNA biosynthesis KW - Acquired immune deficiency syndrome KW - Zidovudine KW - Mitochondria KW - Toxicity KW - DNA repair KW - Antiviral agents KW - Human immunodeficiency virus KW - DNA-directed DNA polymerase KW - X 24117:Biochemistry KW - N 14653:Effect of antibiotics, antimetabolites & mutagens KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Differential+Incorporation+and+Removal+of+Antiviral+Deoxynucleotides+by+Human+DNA+Polymerase+gamma&rft.au=Lim%2C+SE%3BCopeland%2C+W+C&rft.aulast=Lim&rft.aufirst=SE&rft.date=2001-06-29&rft.volume=276&rft.issue=26&rft.spage=23616&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Antiviral agents; Mitochondria; DNA biosynthesis; Zidovudine; DNA-directed DNA polymerase; DNA repair; Toxicity; Acquired immune deficiency syndrome ER - TY - JOUR T1 - Induction of apoptosis in MDR1 expressing cells by daunorubicin with combinations of suboptimal concentrations of P-glycoprotein modulators. AN - 70856370; 11369136 AB - The application of most agents with the capacity to reverse multidrug resistance (MDR) via modulation of the multidrug transporter P-glycoprotein (Pgp) was shown to be associated with toxic side-effects. For this reason, we have investigated the effect of combinations of suboptimal concentrations of Pgp blockers on the induction of apoptosis and growth arrest in daunorubicin (D) treated, MDR1 gene transfected cells. We used verapamil, PSC833 and Cremophor EL as Pgp modulators, which affect the function of Pgp by different mechanisms. Treatment of NIH3T3/MDR1 cells with combinations of suboptimal concentrations of Pgp modulators in the presence of D caused apoptosis and G(2) arrest to the same extent as optimal concentrations of singly used blockers. We conclude that combinations of suboptimal concentrations of Pgp modulators may cause effective sensitization of resistant tumor cells, and at the same time, may avoid the frequently observed toxic effects experienced in clinical trials with a single modifier applied at the optimal dose. JF - Cancer letters AU - Aszalos, A AU - Ladányi, A AU - Bocsi, J AU - Szende, B AD - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/06/26/ PY - 2001 DA - 2001 Jun 26 SP - 157 EP - 162 VL - 167 IS - 2 SN - 0304-3835, 0304-3835 KW - Antibiotics, Antineoplastic KW - 0 KW - Cyclosporins KW - Drug Combinations KW - P-Glycoprotein KW - cremophor EL KW - 6D4M1DAL6O KW - Verapamil KW - CJ0O37KU29 KW - Glycerol KW - PDC6A3C0OX KW - valspodar KW - Q7ZP55KF3X KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Animals KW - 3T3 Cells KW - G2 Phase -- drug effects KW - Drug Interactions KW - Glycerol -- analogs & derivatives KW - Cell Division -- drug effects KW - Mice KW - Verapamil -- pharmacology KW - Glycerol -- pharmacology KW - Daunorubicin -- pharmacology KW - Apoptosis KW - Antibiotics, Antineoplastic -- pharmacology KW - Cyclosporins -- pharmacology KW - P-Glycoprotein -- biosynthesis KW - P-Glycoprotein -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70856370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Induction+of+apoptosis+in+MDR1+expressing+cells+by+daunorubicin+with+combinations+of+suboptimal+concentrations+of+P-glycoprotein+modulators.&rft.au=Aszalos%2C+A%3BLad%C3%A1nyi%2C+A%3BBocsi%2C+J%3BSzende%2C+B&rft.aulast=Aszalos&rft.aufirst=A&rft.date=2001-06-26&rft.volume=167&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agricultural exposure history among African-American farmers in Georgia. AN - 70966571; 11437057 AB - Agricultural exposures differ across the United States by region, calendar time period, and agricultural practice, but most of the published literature focuses on white men in the Midwest. A pilot study was conducted to explore the breadth and diversity of farming practices over time among African-American farmers in Georgia whose exposures may differ in important ways. Using a comprehensive life events calendar questionnaire, 17 male African-American farmers aged 36 to 86 yr residing in southeastern Georgia were interviewed regarding their agricultural history in July 1997. Most men (15/17) reported working on multiple farms in their lifetime; 3 men worked on 5 different farms during their lifetime. These farmers reported using more chemicals during their lifetime than farmers in the Midwest. Used motor oil was the most frequently reported insecticide applied to animals; this apparently common practice has not been described in the literature and should be better understood since its use may result in dermal exposure to polyaromatic hydrocarbons. Better characterization of regionally specific farming history and individual farming practices will facilitate studies of the health effects of farming. JF - Journal of toxicology and environmental health. Part A AU - Hoppin, J A AU - Guzman, J D AU - Tolbert, P E AU - Flagg, E W AD - Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. hoppin1@niehs.nih.gov Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 SP - 237 EP - 241 VL - 63 IS - 4 SN - 1528-7394, 1528-7394 KW - Pesticides KW - 0 KW - Index Medicus KW - Georgia -- epidemiology KW - Aged, 80 and over KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Aged KW - African Americans KW - Middle Aged KW - Data Collection KW - Male KW - Occupational Exposure -- statistics & numerical data KW - Agricultural Workers' Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70966571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Agricultural+exposure+history+among+African-American+farmers+in+Georgia.&rft.au=Hoppin%2C+J+A%3BGuzman%2C+J+D%3BTolbert%2C+P+E%3BFlagg%2C+E+W&rft.aulast=Hoppin&rft.aufirst=J&rft.date=2001-06-22&rft.volume=63&rft.issue=4&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of the hepatitis B virus X protein with the Crm1-dependent nuclear export pathway. AN - 70923023; 11287420 AB - The leucine-rich nuclear export signal (NES) is used to shuttle large cellular proteins from the nucleus to the cytoplasm. The nuclear export receptor Crm1 is essential in this process by recognizing the NES motif. Here, we show that the oncogenic hepatitis B virus (HBV) X protein (HBx) contains a functional NES motif. We found that the predominant cytoplasmic localization of HBx is sensitive to the drug leptomycin B (LMB), which specifically inactivates Crm1. Mutations at the two conserved leucine residues to alanine at the NES motif (L98A,L100A) resulted in a nuclear redistribution of HBx. A recombinant HBx protein binds to Crm1 in vitro. In addition, ectopic expression of HBx sequesters Crm1 in the cytoplasm. Furthermore, HBx activates NFkappaB by inducing its nuclear translocation in a NES-dependent manner. Abnormal cytoplasmic sequestration of Crm1, accompanied by a nuclear localization of NFkappaB, was also observed in hepatocytes from HBV-positive liver samples with chronic active hepatitis. We suggest that Crm1 may play a role in HBx-mediated liver carcinogenesis. JF - The Journal of biological chemistry AU - Forgues, M AU - Marrogi, A J AU - Spillare, E A AU - Wu, C G AU - Yang, Q AU - Yoshida, M AU - Wang, X W AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 SP - 22797 EP - 22803 VL - 276 IS - 25 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - DNA Primers KW - Karyopherins KW - NF-kappa B KW - Receptors, Cytoplasmic and Nuclear KW - Trans-Activators KW - exportin 1 protein KW - hepatitis B virus X protein KW - Index Medicus KW - Liver -- virology KW - Liver Neoplasms -- pathology KW - Base Sequence KW - Cytoplasm -- metabolism KW - Humans KW - Hepatitis B virus -- isolation & purification KW - Liver -- metabolism KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Transformation, Neoplastic KW - Protein Transport KW - NF-kappa B -- metabolism KW - Trans-Activators -- metabolism KW - Carrier Proteins -- metabolism KW - Trans-Activators -- genetics KW - Cell Nucleus -- metabolism KW - Carrier Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70923023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Interaction+of+the+hepatitis+B+virus+X+protein+with+the+Crm1-dependent+nuclear+export+pathway.&rft.au=Forgues%2C+M%3BMarrogi%2C+A+J%3BSpillare%2C+E+A%3BWu%2C+C+G%3BYang%2C+Q%3BYoshida%2C+M%3BWang%2C+X+W&rft.aulast=Forgues&rft.aufirst=M&rft.date=2001-06-22&rft.volume=276&rft.issue=25&rft.spage=22797&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Toxicity of metals: Role of oxidative stress-mediated mechanisms AN - 39474010; 3606134 AU - Kadiiska, M B AU - Waalkes, M P AU - Liu, J AU - Mason, R P Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39474010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Toxicity+of+metals%3A+Role+of+oxidative+stress-mediated+mechanisms&rft.au=Kadiiska%2C+M+B%3BWaalkes%2C+M+P%3BLiu%2C+J%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Reston, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. #1563 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Comparing the names and pictures of objects: A one-back fMRI study AN - 39438401; 3600177 AU - Sevostianov, A AU - Horwitz, B AU - Nechaev, V AU - Fromm, S AU - Braun, A Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39438401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Comparing+the+names+and+pictures+of+objects%3A+A+one-back+fMRI+study&rft.au=Sevostianov%2C+A%3BHorwitz%2C+B%3BNechaev%2C+V%3BFromm%2C+S%3BBraun%2C+A&rft.aulast=Sevostianov&rft.aufirst=A&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns. Poster Paper No. 91F N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Polymorphisms in DNA repair genes: Modulation of damage in erythrocytes and lymphocytes AN - 39423520; 3606103 AU - Bell, DA AU - Watson, M AU - Helzlsouer, K AU - Lunn, R M Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39423520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Polymorphisms+in+DNA+repair+genes%3A+Modulation+of+damage+in+erythrocytes+and+lymphocytes&rft.au=Bell%2C+DA%3BWatson%2C+M%3BHelzlsouer%2C+K%3BLunn%2C+R+M&rft.aulast=Bell&rft.aufirst=DA&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Reston, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. #1559 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Catalytic functions of tyrosyl radicals and their interactions with nitric oxide AN - 39403456; 3606148 AU - Sturgeon, B E AU - Glover, R E AU - Chen, Y AU - Burka, L T AU - Mason, R P Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39403456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Catalytic+functions+of+tyrosyl+radicals+and+their+interactions+with+nitric+oxide&rft.au=Sturgeon%2C+B+E%3BGlover%2C+R+E%3BChen%2C+Y%3BBurka%2C+L+T%3BMason%2C+R+P&rft.aulast=Sturgeon&rft.aufirst=B&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Reston, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. #1874 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Challenges in application of microarray data to develop predictive mechanistic information of toxicants AN - 39403308; 3606106 AU - Afshari, CA Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39403308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Challenges+in+application+of+microarray+data+to+develop+predictive+mechanistic+information+of+toxicants&rft.au=Afshari%2C+CA&rft.aulast=Afshari&rft.aufirst=CA&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Reston, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. #23 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Evaluation of two RAS gene transgenic models, RASH2 and TG.AC AN - 39403124; 3606231 AU - Tennant, R W Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39403124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Evaluation+of+two+RAS+gene+transgenic+models%2C+RASH2+and+TG.AC&rft.au=Tennant%2C+R+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Reston, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. #1883 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dissociation between task timing and task order anticipation during task switching AN - 39390793; 3599612 AU - Dreher, J-C AU - Koechlin, E AU - Ali, O AU - Grafman, J Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39390793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dissociation+between+task+timing+and+task+order+anticipation+during+task+switching&rft.au=Dreher%2C+J-C%3BKoechlin%2C+E%3BAli%2C+O%3BGrafman%2C+J&rft.aulast=Dreher&rft.aufirst=J-C&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns. Poster Paper No. 28B N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Detection of chromosomal aberrations in cancer screening samples by interphase cytogenetics with tumor and tumor stage specific probes leads to early and refined diagnosis AN - 39376708; 3612468 AU - Heselmeyer-Haddad, K M AU - Fehm, T AU - Djavidan, M AU - Ghadimi, B M AU - Wilber, K AU - Morrison, L AU - Sherman, M AU - Uhr, J AU - Auer, G AU - Ried, T Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39376708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Detection+of+chromosomal+aberrations+in+cancer+screening+samples+by+interphase+cytogenetics+with+tumor+and+tumor+stage+specific+probes+leads+to+early+and+refined+diagnosis&rft.au=Heselmeyer-Haddad%2C+K+M%3BFehm%2C+T%3BDjavidan%2C+M%3BGhadimi%2C+B+M%3BWilber%2C+K%3BMorrison%2C+L%3BSherman%2C+M%3BUhr%2C+J%3BAuer%2C+G%3BRied%2C+T&rft.aulast=Heselmeyer-Haddad&rft.aufirst=K&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: European Society for Analytical Cellular Pathology, URL: rex.iutcaen.unicaen.fr/7esacp. Paper No. N001 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Individual differences in strategy preference and associated cerebral blood flow during route information recall AN - 39376472; 3599606 AU - Manly, C F AU - Romero, S G AU - Harris, A AU - Lobo, A-M AU - Makale, M AU - Grafman, J Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39376472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Individual+differences+in+strategy+preference+and+associated+cerebral+blood+flow+during+route+information+recall&rft.au=Manly%2C+C+F%3BRomero%2C+S+G%3BHarris%2C+A%3BLobo%2C+A-M%3BMakale%2C+M%3BGrafman%2C+J&rft.aulast=Manly&rft.aufirst=C&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns. Poster Paper No. 22B N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Perirhinal cortex resolves feature ambiguity in complex visual discriminations AN - 39366731; 3599674 AU - Murray, E A AU - Bussey, T J AU - Saksida, L M Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39366731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Perirhinal+cortex+resolves+feature+ambiguity+in+complex+visual+discriminations&rft.au=Murray%2C+E+A%3BBussey%2C+T+J%3BSaksida%2C+L+M&rft.aulast=Murray&rft.aufirst=E&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns. Poster Paper No. 103B N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Exploring neural aspects of transcranial magnetic stimulation (TMS) within a modeling framework AN - 39360645; 3599628 AU - Husain, F T AU - Tagamets, MA AU - Braun, A R AU - Horwitz, B Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39360645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Exploring+neural+aspects+of+transcranial+magnetic+stimulation+%28TMS%29+within+a+modeling+framework&rft.au=Husain%2C+F+T%3BTagamets%2C+MA%3BBraun%2C+A+R%3BHorwitz%2C+B&rft.aulast=Husain&rft.aufirst=F&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns. Poster Paper No. 44B N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Misregulation of iron metabolism and neurodegenerative disease in mice that lack iron regulatory protein 2 AN - 39350868; 3602858 AU - Rouault, T Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39350868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Misregulation+of+iron+metabolism+and+neurodegenerative+disease+in+mice+that+lack+iron+regulatory+protein+2&rft.au=Rouault%2C+T&rft.aulast=Rouault&rft.aufirst=T&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Gordon Research Conferences, P.O. Box 984, West Kingston, RI 02892-0984, USA; phone: 401-783-4011; fax: 401-783-7644; email: grc@grcmail.grc.uri.edu; URL: www.grc.uri.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Activation of Broca's area during language production by speech and American sign language (ASL): Cytoarchitectonic mapping and PET AN - 39338596; 3600196 AU - Horwitz, B AU - Amunts, K AU - Bhattacharyya, R AU - Patkin, D AU - Braun, A Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39338596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Activation+of+Broca%27s+area+during+language+production+by+speech+and+American+sign+language+%28ASL%29%3A+Cytoarchitectonic+mapping+and+PET&rft.au=Horwitz%2C+B%3BAmunts%2C+K%3BBhattacharyya%2C+R%3BPatkin%2C+D%3BBraun%2C+A&rft.aulast=Horwitz&rft.aufirst=B&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns. Poster Paper No. 110F N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Distributed, topographically-organized representation of objects in ventral temporal cortex AN - 39336999; 3599448 AU - Haxby, J Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39336999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Distributed%2C+topographically-organized+representation+of+objects+in+ventral+temporal+cortex&rft.au=Haxby%2C+J&rft.aulast=Haxby&rft.aufirst=J&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Nueroscience Society, 6162 Moore Hall, Dartmouth College, Hanover, NH 03755, USA; phone: 603-646-1189; email: cns@dartmouth.edu; URL: www.dartmouth.edu/~cns N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Animal models for ovarian toxicity AN - 39329267; 3606209 AU - Davis, B J Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39329267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Animal+models+for+ovarian+toxicity&rft.au=Davis%2C+B+J&rft.aulast=Davis&rft.aufirst=B&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Reston, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. #1570 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Limited in vivo metabolism of n-3 fatty acids and implications for mammalian neurodevelopment and brain phospholipid function AN - 39302424; 3605145 AU - Salem, N Jr Y1 - 2001/06/22/ PY - 2001 DA - 2001 Jun 22 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39302424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Limited+in+vivo+metabolism+of+n-3+fatty+acids+and+implications+for+mammalian+neurodevelopment+and+brain+phospholipid+function&rft.au=Salem%2C+N+Jr&rft.aulast=Salem&rft.aufirst=N&rft.date=2001-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Oil Chemists' Society, P.O. Box 3489, Champaign, IL 61826-3489, USA; phone: (217) 359-2344; fax: (217) 351-8091; URL: aocs.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Distinctive gene expression profiles associated with Hepatitis B virus x protein. AN - 70978002; 11439330 AB - Hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV encodes the potentially oncogenic HBx protein, which mainly functions as a transcriptional co-activator involving in multiple gene deregulations. However, mechanisms underlying HBx-mediated oncogenicity remain unclear. To determine the role(s) of HBx in the early genesis of HCC, we utilized the NCI Oncochip microarray that contains 2208 human cDNA clones to examine the gene expression profiles in either freshly isolated normal primary adult human hepatocytes (Hhep) or an HCC cell line (SK-Hep-1) ecotopically expressing HBx via an adenoviral system. The gene expression profiles also were determined in liver samples from HBV-infected chronic active hepatitis patients when compared with normal liver samples. The microarray results were validated through Northern blot analysis of the expression of selected genes. Using reciprocally labeling hybridizations, scatterplot analysis of gene expression ratios in human primary hepatocytes expressing HBx demonstrates that microarrays are highly reproducible. The comparison of gene expression profiles between HBx-expressing primary hepatocytes and HBV-infected liver samples shows a consistent alteration of many cellular genes including a subset of oncogenes (such as c-myc and c-myb) and tumor suppressor genes (such as APC, p53, WAF1 and WT1). Furthermore, clustering algorithm analysis showed distinctive gene expression profiles in Hhep and SK-Hep-1 cells. Our findings are consistent with the hypothesis that the deregulation of cellular genes by oncogenic HBx may be an early event that favors hepatocyte proliferation during liver carcinogenesis. JF - Oncogene AU - Wu, C G AU - Salvay, D M AU - Forgues, M AU - Valerie, K AU - Farnsworth, J AU - Markin, R S AU - Wang, X W AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland, MD 20892-4255, USA. Y1 - 2001/06/21/ PY - 2001 DA - 2001 Jun 21 SP - 3674 EP - 3682 VL - 20 IS - 28 SN - 0950-9232, 0950-9232 KW - Carbocyanines KW - 0 KW - Fluorescent Dyes KW - Trans-Activators KW - cyanine dye 3 KW - cyanine dye 5 KW - hepatitis B virus X protein KW - Index Medicus KW - Liver -- pathology KW - Tumor Cells, Cultured KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Adult KW - Staining and Labeling -- methods KW - Gene Expression KW - Freezing KW - Blotting, Northern -- methods KW - Hepatocytes -- cytology KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Profiling KW - Trans-Activators -- biosynthesis KW - Hepatitis B virus KW - Trans-Activators -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Hepatitis B, Chronic -- pathology KW - Hepatitis B, Chronic -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70978002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Distinctive+gene+expression+profiles+associated+with+Hepatitis+B+virus+x+protein.&rft.au=Wu%2C+C+G%3BSalvay%2C+D+M%3BForgues%2C+M%3BValerie%2C+K%3BFarnsworth%2C+J%3BMarkin%2C+R+S%3BWang%2C+X+W&rft.aulast=Wu&rft.aufirst=C&rft.date=2001-06-21&rft.volume=20&rft.issue=28&rft.spage=3674&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. AN - 70966714; 11439325 AB - Chronic hepatitis B virus (HBV) infection and the integration of its X gene (HBx) are closely associated with the development of hepatocellular carcinoma (HCC). The integrated HBx frequently is truncated or contains point mutations. Previous studies indicated that these HBx mutants have a diminished co-transactivational activity. We have compared the effects of wild-type (wt) HBx and its naturally occurring mutants derived from human HCCs on transcriptional co-transactivation, apoptosis and interactive effects with p53. We demonstrated that overexpression of mutant, but not wt HBx, is defective in transcriptional co-transactivation of the NF-kappaB-driven luciferase reporter. By using a microinjection technique, the HBx mutants were shown to have an attenuated pro-apoptotic activity. This deficiency may be attributed to multiple mutations in the co-transactivation domain of HBx, that leads to decreased stability of the translated product. However, wt or mutant HBx bind to p53 in vitro and retain their ability to block p53-mediated apoptosis in vivo, which has been implicated as its major tumor suppressor function. The abrogation of p53-mediated apoptosis by integrated HBx mutants may provide a selective clonal advantage for preneoplastic or neoplastic hepatocytes and contribute to hepatocellular carcinogenesis. JF - Oncogene AU - Huo, T I AU - Wang, X W AU - Forgues, M AU - Wu, C G AU - Spillare, E A AU - Giannini, C AU - Brechot, C AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892 USA. Y1 - 2001/06/21/ PY - 2001 DA - 2001 Jun 21 SP - 3620 EP - 3628 VL - 20 IS - 28 SN - 0950-9232, 0950-9232 KW - NF-kappa B KW - 0 KW - Trans-Activators KW - Tumor Suppressor Protein p53 KW - hepatitis B virus X protein KW - Luciferases KW - EC 1.13.12.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - COS Cells KW - Humans KW - Glutathione Transferase -- metabolism KW - Amino Acid Sequence KW - Transcriptional Activation KW - Cercopithecus aethiops KW - Genes, Reporter KW - Molecular Sequence Data KW - Luciferases -- genetics KW - Mutation KW - Cell Line KW - NF-kappa B -- metabolism KW - Hepatitis B virus -- metabolism KW - Carcinoma, Hepatocellular -- virology KW - Trans-Activators -- metabolism KW - Apoptosis KW - Trans-Activators -- genetics KW - Hepatitis B, Chronic -- virology KW - Liver Neoplasms -- virology KW - Hepatitis B virus -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70966714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Hepatitis+B+virus+X+mutants+derived+from+human+hepatocellular+carcinoma+retain+the+ability+to+abrogate+p53-induced+apoptosis.&rft.au=Huo%2C+T+I%3BWang%2C+X+W%3BForgues%2C+M%3BWu%2C+C+G%3BSpillare%2C+E+A%3BGiannini%2C+C%3BBrechot%2C+C%3BHarris%2C+C+C&rft.aulast=Huo&rft.aufirst=T&rft.date=2001-06-21&rft.volume=20&rft.issue=28&rft.spage=3620&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenserine regulates translation of beta -amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development. AN - 70939683; 11404470 AB - The reduction in levels of the potentially toxic amyloid-beta peptide (Abeta) has emerged as one of the most important therapeutic goals in Alzheimer's disease. Key targets for this goal are factors that affect the expression and processing of the Abeta precursor protein (betaAPP). Earlier reports from our laboratory have shown that a novel cholinesterase inhibitor, phenserine, reduces betaAPP levels in vivo. Herein, we studied the mechanism of phenserine's actions to define the regulatory elements in betaAPP processing. Phenserine treatment resulted in decreased secretion of soluble betaAPP and Abeta into the conditioned media of human neuroblastoma cells without cellular toxicity. The regulation of betaAPP protein expression by phenserine was posttranscriptional as it suppressed betaAPP protein expression without altering betaAPP mRNA levels. However, phenserine's action was neither mediated through classical receptor signaling pathways, involving extracellular signal-regulated kinase or phosphatidylinositol 3-kinase activation, nor was it associated with the anticholinesterase activity of the drug. Furthermore, phenserine reduced expression of a chloramphenicol acetyltransferase reporter fused to the 5'-mRNA leader sequence of betaAPP without altering expression of a control chloramphenicol acetyltransferase reporter. These studies suggest that phenserine reduces Abeta levels by regulating betaAPP translation via the recently described iron regulatory element in the 5'-untranslated region of betaAPP mRNA, which has been shown previously to be up-regulated in the presence of interleukin-1. This study identifies an approach for the regulation of betaAPP expression that can result in a substantial reduction in the level of Abeta. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Shaw, K T AU - Utsuki, T AU - Rogers, J AU - Yu, Q S AU - Sambamurti, K AU - Brossi, A AU - Ge, Y W AU - Lahiri, D K AU - Greig, N H AD - Drug Design and Development, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA. Y1 - 2001/06/19/ PY - 2001 DA - 2001 Jun 19 SP - 7605 EP - 7610 VL - 98 IS - 13 SN - 0027-8424, 0027-8424 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - 5' Untranslated Regions KW - Amyloid beta-Protein Precursor KW - Cholinesterase Inhibitors KW - Chromones KW - Culture Media, Conditioned KW - Enzyme Inhibitors KW - Flavonoids KW - Interleukin-1 KW - Morpholines KW - RNA, Messenger KW - Recombinant Proteins KW - phenserine KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Physostigmine KW - 9U1VM840SP KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - 5' Untranslated Regions -- genetics KW - Recombinant Proteins -- biosynthesis KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Astrocytoma KW - Mitogen-Activated Protein Kinases -- metabolism KW - L-Lactate Dehydrogenase -- analysis KW - Humans KW - Morpholines -- pharmacology KW - Chloramphenicol O-Acetyltransferase -- analysis KW - Drug Design KW - Neuroblastoma KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Chromones -- pharmacology KW - Transfection KW - Enzyme Inhibitors -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Flavonoids -- pharmacology KW - Interleukin-1 -- physiology KW - Cholinesterase Inhibitors -- pharmacology KW - Protein Biosynthesis -- drug effects KW - Interleukin-1 -- pharmacology KW - RNA, Messenger -- metabolism KW - Physostigmine -- pharmacology KW - Physostigmine -- analogs & derivatives KW - RNA, Messenger -- genetics KW - Amyloid beta-Protein Precursor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70939683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Phenserine+regulates+translation+of+beta+-amyloid+precursor+protein+mRNA+by+a+putative+interleukin-1+responsive+element%2C+a+target+for+drug+development.&rft.au=Shaw%2C+K+T%3BUtsuki%2C+T%3BRogers%2C+J%3BYu%2C+Q+S%3BSambamurti%2C+K%3BBrossi%2C+A%3BGe%2C+Y+W%3BLahiri%2C+D+K%3BGreig%2C+N+H&rft.aulast=Shaw&rft.aufirst=K&rft.date=2001-06-19&rft.volume=98&rft.issue=13&rft.spage=7605&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurosci. 1998 Mar 1;18(5):1743-52 [9464999] J Biol Chem. 1998 Feb 6;273(6):3740-6 [9452506] Am J Pathol. 1998 Apr;152(4):983-92 [9546359] Neuroreport. 1998 Jan 5;9(1):171-6 [9592071] Brain Res Mol Brain Res. 1998 Nov 20;62(2):131-40 [9813282] J Biol Chem. 1999 Mar 5;274(10):6421-31 [10037734] J Biochem. 1999 Jul;126(1):235-42 [10393344] Science. 1999 Oct 22;286(5440):735-41 [10531052] Nature. 1999 Dec 2;402(6761):533-7 [10591213] Nature. 1999 Dec 2;402(6761):537-40 [10591214] Mol Cell Neurosci. 1999 Dec;14(6):419-27 [10656250] Neurobiol Aging. 2000 May-Jun;21(3):383-421 [10858586] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7606-10 [2508093] Proc Natl Acad Sci U S A. 1990 Aug;87(15):6003-6 [2116015] Cell Mol Neurobiol. 1990 Dec;10(4):485-95 [2091832] J Neurochem. 1992 Apr;58(4):1191-8 [1548459] Science. 1992 Oct 9;258(5080):304-7 [1411529] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10075-8 [1359534] J Biol Chem. 1993 Mar 15;268(8):5974-8 [8449958] J Biol Chem. 1993 Jun 15;268(17):12699-705 [8509404] Ann N Y Acad Sci. 1993 Sep 24;695:15-8 [8239275] J Biol Chem. 1993 Dec 25;268(36):27363-70 [8262977] EMBO J. 1994 Feb 1;13(3):534-42 [8313898] J Biol Chem. 1994 Mar 18;269(11):8376-82 [8132561] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4489-93 [8183935] Science. 1994 May 27;264(5163):1336-40 [8191290] FEBS Lett. 1994 Aug 1;349(2):210-4 [8050568] Med Res Rev. 1995 Jan;15(1):3-31 [7898167] J Biol Chem. 1995 Oct 6;270(40):23243-5 [7559474] J Neurochem. 1995 Oct;65(4):1431-44 [7561836] Brain Res Mol Brain Res. 1995 Sep;32(2):233-40 [7500834] Curr Opin Cell Biol. 1995 Dec;7(6):798-805 [8608010] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82 [8710843] J Biol Chem. 1996 Sep 27;271(39):24226-30 [8798666] J Biol Chem. 1996 Oct 4;271(40):24670-4 [8798734] Neurobiol Aging. 1996 Sep-Oct;17(5):789-94 [8892353] Exp Cell Res. 1996 Nov 25;229(1):93-9 [8940253] Science. 1997 Jan 31;275(5300):630-1 [9019820] J Neurochem. 1997 Jun;68(6):2523-9 [9166748] Brain Res Mol Brain Res. 1997 Jun;46(1-2):161-8 [9191090] Ann N Y Acad Sci. 1997 Sep 26;826:416-21 [9329715] Brain Res Brain Res Rev. 1997 Sep 30;25(1):50-69 [9370050] J Neurochem. 1998 Feb;70(2):524-30 [9453546] J Neurosci. 1998 Apr 15;18(8):2907-13 [9526007] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. AN - 70935066; 11390984 AB - Clear cell-type renal cell carcinomas (clear RCC) are characterized almost universally by loss of heterozygosity on chromosome 3p, which usually involves any combination of three regions: 3p25-p26 (harboring the VHL gene), 3p12-p14.2 (containing the FHIT gene), and 3p21-p22, implying inactivation of the resident tumor-suppressor genes (TSGs). For the 3p21-p22 region, the affected TSGs remain, at present, unknown. Recently, the RAS association family 1 gene (isoform RASSF1A), located at 3p21.3, has been identified as a candidate lung and breast TSG. In this report, we demonstrate aberrant silencing by hypermethylation of RASSF1A in both VHL-caused clear RCC tumors and clear RCC without VHL inactivation. We found hypermethylation of RASSF1A's GC-rich putative promoter region in most of analyzed samples, including 39 of 43 primary tumors (91%). The promoter was methylated partially or completely in all 18 RCC cell lines analyzed. Methylation of the GC-rich putative RASSF1A promoter region and loss of transcription of the corresponding mRNA were related causally. RASSF1A expression was reactivated after treatment with 5-aza-2'-deoxycytidine. Forced expression of RASSF1A transcripts in KRC/Y, a renal carcinoma cell line containing a normal and expressed VHL gene, suppressed growth on plastic dishes and anchorage-independent colony formation in soft agar. Mutant RASSF1A had reduced growth suppression activity significantly. These data suggest that RASSF1A is the candidate renal TSG gene for the 3p21.3 region. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dreijerink, K AU - Braga, E AU - Kuzmin, I AU - Geil, L AU - Duh, F M AU - Angeloni, D AU - Zbar, B AU - Lerman, M I AU - Stanbridge, E J AU - Minna, J D AU - Protopopov, A AU - Li, J AU - Kashuba, V AU - Klein, G AU - Zabarovsky, E R AD - Laboratory of Immunobiology and Intramural Research Support Program, Science Applications International Corporation, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/06/19/ PY - 2001 DA - 2001 Jun 19 SP - 7504 EP - 7509 VL - 98 IS - 13 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Neoplasm Proteins KW - RASSF1 protein, human KW - Recombinant Proteins KW - Tumor Suppressor Proteins KW - Azacitidine KW - M801H13NRU KW - Doxycycline KW - N12000U13O KW - Index Medicus KW - Azacitidine -- pharmacology KW - Humans KW - Cell Division -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Chromosome Mapping KW - Doxycycline -- toxicity KW - Gene Expression Regulation, Neoplastic -- drug effects KW - DNA, Neoplasm -- chemistry KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - DNA Methylation KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - DNA, Neoplasm -- metabolism KW - Cell Adhesion KW - Kidney Neoplasms -- genetics KW - Chromosomes, Human, Pair 3 KW - Genes, Tumor Suppressor KW - Neoplasm Proteins -- genetics KW - Neoplasm Proteins -- metabolism KW - Carcinoma, Renal Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70935066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+candidate+tumor+suppressor+gene%2C+RASSF1A%2C+from+human+chromosome+3p21.3+is+involved+in+kidney+tumorigenesis.&rft.au=Dreijerink%2C+K%3BBraga%2C+E%3BKuzmin%2C+I%3BGeil%2C+L%3BDuh%2C+F+M%3BAngeloni%2C+D%3BZbar%2C+B%3BLerman%2C+M+I%3BStanbridge%2C+E+J%3BMinna%2C+J+D%3BProtopopov%2C+A%3BLi%2C+J%3BKashuba%2C+V%3BKlein%2C+G%3BZabarovsky%2C+E+R&rft.aulast=Dreijerink&rft.aufirst=K&rft.date=2001-06-19&rft.volume=98&rft.issue=13&rft.spage=7504&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FEBS Lett. 1999 Nov 26;462(1-2):121-8 [10580104] Am J Med. 1964 Apr;36:595-617 [14142412] J Med Genet. 2000 May;37(5):348-53 [10807693] Nat Genet. 2000 Jul;25(3):315-9 [10888881] Oncology. 2000 Aug;59(2):126-30 [10971171] Cancer Res. 2000 Nov 1;60(21):6116-33 [11085536] J Biol Chem. 2000 Nov 17;275(46):35669-72 [10998413] Oncogene. 2001 Mar 22;20(12):1509-18 [11313894] J Natl Cancer Inst. 2001 May 2;93(9):691-9 [11333291] Cancer Genet Cytogenet. 1988 Dec;36(2):197-202 [3203309] J Med Genet. 1990 May;27(5):311-4 [2352258] Cancer Res. 1991 Sep 1;51(17):4707-11 [1678685] Genomics. 1991 Nov;11(3):537-42 [1685475] Science. 1993 May 28;260(5112):1317-20 [8493574] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3383-7 [8159756] Hum Mol Genet. 1994 Feb;3(2):390 [7911705] Cancer Res. 1994 Jul 15;54(14):3710-3 [8033088] Nat Genet. 1994 May;7(1):85-90 [7915601] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9700-4 [7937876] J Clin Epidemiol. 1995 Jun;48(6):767-77 [7769407] Genes Chromosomes Cancer. 1996 Jan;15(1):64-72 [8824727] Lancet. 1997 Mar 22;349(9055):848-9 [9121264] Nucleic Acids Res. 1997 Jun 15;25(12):2532-4 [9171110] Genes Chromosomes Cancer. 1997 Jun;19(2):59-76 [9171996] Genes Chromosomes Cancer. 1997 Aug;19(4):228-32 [9258657] Cancer Res. 1998 Jul 15;58(14):2946-51 [9679951] FEBS Lett. 1999 Jul 9;454(3):215-9 [10431810] Oncogene. 1999 Oct 7;18(41):5672-9 [10523847] Oncogene. 2000 Mar 9;19(11):1392-9 [10723130] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine receptor regulating factor, DRRF: a zinc finger transcription factor. AN - 70934827; 11390978 AB - Dopamine receptor genes are under complex transcription control, determining their unique regional distribution in the brain. We describe here a zinc finger type transcription factor, designated dopamine receptor regulating factor (DRRF), which binds to GC and GT boxes in the D1A and D2 dopamine receptor promoters and effectively displaces Sp1 and Sp3 from these sequences. Consequently, DRRF can modulate the activity of these dopamine receptor promoters. Highest DRRF mRNA levels are found in brain with a specific regional distribution including olfactory bulb and tubercle, nucleus accumbens, striatum, hippocampus, amygdala, and frontal cortex. Many of these brain regions also express abundant levels of various dopamine receptors. In vivo, DRRF itself can be regulated by manipulations of dopaminergic transmission. Mice treated with drugs that increase extracellular striatal dopamine levels (cocaine), block dopamine receptors (haloperidol), or destroy dopamine terminals (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) show significant alterations in DRRF mRNA. The latter observations provide a basis for dopamine receptor regulation after these manipulations. We conclude that DRRF is important for modulating dopaminergic transmission in the brain. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hwang, C K AU - D'Souza, U M AU - Eisch, A J AU - Yajima, S AU - Lammers, C H AU - Yang, Y AU - Lee, S H AU - Kim, Y M AU - Nestler, E J AU - Mouradian, M M AD - Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 2001/06/19/ PY - 2001 DA - 2001 Jun 19 SP - 7558 EP - 7563 VL - 98 IS - 13 SN - 0027-8424, 0027-8424 KW - Dopamine Antagonists KW - 0 KW - Klf16 protein, mouse KW - Kruppel-Like Transcription Factors KW - RNA, Messenger KW - Receptors, Dopamine KW - Transcription Factors KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Cocaine KW - I5Y540LHVR KW - Haloperidol KW - J6292F8L3D KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Corpus Striatum -- metabolism KW - Dopamine Antagonists -- pharmacology KW - RNA, Messenger -- analysis KW - Dopamine -- metabolism KW - Mice KW - Amino Acid Sequence KW - Autoradiography KW - Neuroblastoma KW - In Situ Hybridization KW - Tumor Cells, Cultured KW - Sequence Alignment KW - Conserved Sequence KW - Down-Regulation KW - Transfection KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Haloperidol -- pharmacology KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Zinc Fingers KW - Sequence Homology, Amino Acid KW - Cocaine -- pharmacology KW - Male KW - Cell Line KW - Neurons -- metabolism KW - Gene Expression Regulation -- physiology KW - Transcription Factors -- metabolism KW - Transcription Factors -- chemistry KW - Receptors, Dopamine -- genetics KW - Gene Expression Regulation -- drug effects KW - Brain -- metabolism KW - Transcription Factors -- genetics KW - Receptors, Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70934827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Dopamine+receptor+regulating+factor%2C+DRRF%3A+a+zinc+finger+transcription+factor.&rft.au=Hwang%2C+C+K%3BD%27Souza%2C+U+M%3BEisch%2C+A+J%3BYajima%2C+S%3BLammers%2C+C+H%3BYang%2C+Y%3BLee%2C+S+H%3BKim%2C+Y+M%3BNestler%2C+E+J%3BMouradian%2C+M+M&rft.aulast=Hwang&rft.aufirst=C&rft.date=2001-06-19&rft.volume=98&rft.issue=13&rft.spage=7558&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF283891; GENBANK N1 - SuppNotes - Cited By: Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] EMBO J. 1992 Oct;11(10):3663-71 [1356762] Annu Rev Neurosci. 1993;16:299-321 [8460895] Mol Cell Biol. 1993 May;13(5):2776-86 [7682653] J Biol Chem. 1993 Nov 5;268(31):23544-51 [8226883] Brain Res Mol Brain Res. 1993 Sep;19(4):313-7 [8231734] Nature. 1993 Dec 2;366(6454):483-7 [8247159] Nature. 1993 Dec 16;366(6456):690-4 [8259212] J Biochem. 1993 Oct;114(4):605-9 [8276776] FEBS Lett. 1994 Feb 14;339(1-2):63-6 [8313980] J Biol Chem. 1994 Apr 15;269(15):11656-62 [8157698] EMBO J. 1994 Aug 15;13(16):3843-51 [8070411] Science. 1995 Jan 27;267(5197):531-6 [7824954] Mol Cell Biol. 1995 Nov;15(11):5957-65 [7565748] Eur J Pharmacol. 1999 Aug 13;378(3):259-63 [10493101] Synapse. 1999 Dec;34(3):222-7 [10523759] Nucleic Acids Res. 1995 Dec 11;23(23):4907-12 [8532536] Mol Cell Biol. 1996 Apr;16(4):1695-705 [8657145] Eur Neuropsychopharmacol. 1995 Dec;5(4):465-9 [8998398] Synapse. 1996 Jul;23(3):232-5 [8807752] Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10151-5 [8816767] Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11933-8 [8876240] Mol Pharmacol. 1996 Nov;50(5):1073-9 [8913337] J Biol Chem. 1997 Feb 14;272(7):4021-6 [9020109] J Neurosci. 1997 Nov 15;17(22):8657-66 [9348334] J Biol Chem. 1998 Jan 9;273(2):1026-31 [9422764] Neuropharmacology. 1997 Nov-Dec;36(11-12):1689-96 [9517440] DNA Cell Biol. 1998 May;17(5):471-9 [9628590] J Biol Chem. 1998 Oct 23;273(43):28229-37 [9774444] J Biol Chem. 1998 Nov 27;273(48):31784-7 [9822643] Mol Cell Biol. 1999 Jan;19(1):194-204 [9858544] Brain Res. 1999 Jan 30;817(1-2):163-71 [9889359] Immunity. 1999 Jan;10(1):93-103 [10023774] Eur J Pharmacol. 1999 Jun 30;375(1-3):13-30 [10443561] Nucleic Acids Res. 1999 Aug 1;27(15):2991-3000 [10454592] Oncogene. 2000 Apr 6;19(15):1941-9 [10773884] J Biol Chem. 2000 Jul 7;275(27):20734-41 [10764806] J Biol Chem. 2000 Dec 8;275(49):38863-9 [10984499] J Neurochem. 2001 Mar;76(6):1736-44 [11259491] Cell. 1987 Dec 24;51(6):1079-90 [3319186] Science. 1989 Jul 28;245(4916):371-8 [2667136] Cell. 1989 Dec 1;59(5):827-36 [2512012] Science. 1991 May 10;252(5007):809-17 [2028256] Genes Dev. 1991 Sep;5(9):1646-56 [1885006] J Neurosci. 1992 Jun;12(6):2288-302 [1607941] Nucleic Acids Res. 1992 Nov 11;20(21):5519-25 [1454515] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of balloon injury on neointimal hyperplasia in streptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats. AN - 70933386; 11413090 AB - The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals. JF - Circulation AU - Indolfi, C AU - Torella, D AU - Cavuto, L AU - Davalli, A M AU - Coppola, C AU - Esposito, G AU - Carriero, M V AU - Rapacciuolo, A AU - Di Lorenzo, E AU - Stabile, E AU - Perrino, C AU - Chieffo, A AU - Pardo, F AU - Chiariello, M AD - Division of Cardiology, University Federico II, and the National Cancer Institute, Naples, Italy. indolfi@unina.it Y1 - 2001/06/19/ PY - 2001 DA - 2001 Jun 19 SP - 2980 EP - 2986 VL - 103 IS - 24 KW - Blood Glucose KW - 0 KW - Insulin KW - Streptozocin KW - 5W494URQ81 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - ras Proteins KW - EC 3.6.5.2 KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - ras Proteins -- genetics KW - Animals KW - Mitogen-Activated Protein Kinases -- metabolism KW - Insulin -- blood KW - Muscle, Smooth, Vascular -- drug effects KW - Cell Division -- drug effects KW - Disease Models, Animal KW - Insulin -- pharmacology KW - Rats KW - Mutagenesis, Site-Directed KW - Rats, Inbred F344 KW - ras Proteins -- antagonists & inhibitors KW - Glucose -- pharmacology KW - Transfection KW - Cells, Cultured KW - Signal Transduction -- drug effects KW - Rats, Wistar KW - Cell Movement -- drug effects KW - Muscle, Smooth, Vascular -- cytology KW - Muscle, Smooth, Vascular -- enzymology KW - Cell Division -- genetics KW - Hyperplasia -- pathology KW - Carotid Artery Diseases -- pathology KW - Islets of Langerhans Transplantation KW - Hyperinsulinism -- pathology KW - Angioplasty, Balloon -- adverse effects KW - Diabetes Mellitus, Experimental -- metabolism KW - Carotid Artery Diseases -- etiology KW - Carotid Artery Diseases -- genetics KW - Hyperplasia -- etiology KW - Hyperplasia -- genetics KW - Diabetes Mellitus, Experimental -- pathology KW - Hyperinsulinism -- chemically induced KW - Tunica Intima -- metabolism KW - Diabetes Mellitus, Experimental -- chemically induced KW - Hyperinsulinism -- metabolism KW - Tunica Intima -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70933386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Effects+of+balloon+injury+on+neointimal+hyperplasia+in+streptozotocin-induced+diabetes+and+in+hyperinsulinemic+nondiabetic+pancreatic+islet-transplanted+rats.&rft.au=Indolfi%2C+C%3BTorella%2C+D%3BCavuto%2C+L%3BDavalli%2C+A+M%3BCoppola%2C+C%3BEsposito%2C+G%3BCarriero%2C+M+V%3BRapacciuolo%2C+A%3BDi+Lorenzo%2C+E%3BStabile%2C+E%3BPerrino%2C+C%3BChieffo%2C+A%3BPardo%2C+F%3BChiariello%2C+M&rft.aulast=Indolfi&rft.aufirst=C&rft.date=2001-06-19&rft.volume=103&rft.issue=24&rft.spage=2980&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: Population genetics, human serologic response, and gene transcription AN - 17886078; 5131043 AB - Species of pathogenic microbes are composed of an array of evolutionarily distinct chromosomal genotypes characterized by diversity in gene content and sequence (allelic variation). The occurrence of substantial genetic diversity has hindered progress in developing a comprehensive understanding of the molecular basis of virulence and new therapeutics such as vaccines. To provide new information that bears on these issues, 11 genes encoding extracellular proteins in the human bacterial pathogen group A Streptococcus identified by analysis of four genomes were studied. Eight of the 11 genes encode proteins with a LPXTG(L) motif that covalently links Gram-positive virulence factors to the bacterial cell surface. Sequence analysis of the 11 genes in 37 geographically and phylogenetically diverse group A Streptococcus strains cultured from patients with different infection types found that recent horizontal gene transfer has contributed substantially to chromosomal diversity. Regions of the inferred proteins likely to interact with the host were identified by molecular population genetic analysis, and Western immunoblot analysis with sera from infected patients confirmed that they were antigenic. Real-time reverse transcriptase-PCR (TaqMan) assays found that transcription of six of the 11 genes was substantially up-regulated in the stationary phase. In addition, transcription of many genes was influenced by the covR and mga trans-acting gene regulatory loci. Multilocus investigation of putative virulence genes by the integrated approach described herein provides an important strategy to aid microbial pathogenesis research and rapidly identify new targets for therapeutics research. JF - Proceedings of the National Academy of Sciences, USA AU - Reid, S D AU - Green, N M AU - Buss, J K AU - Lei, B AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2001/06/19/ PY - 2001 DA - 2001 Jun 19 SP - 7552 EP - 7557 VL - 98 IS - 13 SN - 0027-8424, 0027-8424 KW - streptococci KW - covR gene KW - mga gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Phylogeny KW - Streptococcus KW - Nucleotide sequence KW - Serology KW - Horizontal transfer KW - Virulence KW - Population genetics KW - Geographical variations KW - N 14555:Miscellaneous KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17886078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Multilocus+analysis+of+extracellular+putative+virulence+proteins+made+by+group+A+Streptococcus%3A+Population+genetics%2C+human+serologic+response%2C+and+gene+transcription&rft.au=Reid%2C+S+D%3BGreen%2C+N+M%3BBuss%2C+J+K%3BLei%2C+B%3BMusser%2C+J+M&rft.aulast=Reid&rft.aufirst=S&rft.date=2001-06-19&rft.volume=98&rft.issue=13&rft.spage=7552&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.121188598 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; Nucleotide sequence; Phylogeny; Geographical variations; Serology; Virulence; Population genetics; Horizontal transfer DO - http://dx.doi.org/10.1073/pnas.121188598 ER - TY - JOUR T1 - Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. AN - 70955800; 11406568 AB - We investigated whether combined treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and trastuzumab could enhance the specific killing of cells that overexpress the erbB-2 receptor. The combination resulted in an enhancement of TRAIL-mediated apoptosis in all cell lines overexpressing erbB-2 receptor compared with either reagent alone. In contrast, there was no effect in cell lines with low levels of the erb-B2 receptor. Trastuzumab treatment resulted in down-regulation of the erbB-2 receptor in all erbB-2-overexpressing cell lines. Similar enhancement of TRAIL toxicity was observed when the erbB-2 receptor was down-regulated using antisense oligodeoxynucleotides. Down-regulation of the erbB-2 receptor protein by trastuzumab or antisense oligodeoxynucleotides decreased Akt kinase activation but not mitogen-activated protein kinase activation. Down-regulation of Akt kinase activity by a phosphatidylinositol 3'-kinase inhibitor (LY294002) also resulted in enhancement of TRAIL-mediated apoptosis. Expression of a constitutively active form of Akt kinase in an erbB-2-overexpressing cell line completely abrogated the increase in TRAIL-mediated apoptosis by trastuzumab and significantly reduced the biological effect of either reagent alone. Therefore, down-regulation of the erbB-2 receptor by trastuzumab enhances TRAIL-mediated apoptosis by inhibiting Akt kinase activity. These data suggest that the combination of trastuzumab and TRAIL may allow enhanced therapeutic efficacy and specificity in the treatment of erbB-2-overexpressing tumors. JF - Cancer research AU - Cuello, M AU - Ettenberg, S A AU - Clark, A S AU - Keane, M M AU - Posner, R H AU - Nau, M M AU - Dennis, P A AU - Lipkowitz, S AD - Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20889, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 4892 EP - 4900 VL - 61 IS - 12 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Antineoplastic Agents KW - Apoptosis Regulatory Proteins KW - Membrane Glycoproteins KW - Proto-Oncogene Proteins KW - Recombinant Fusion Proteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Trastuzumab KW - P188ANX8CK KW - Index Medicus KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Recombinant Fusion Proteins -- pharmacology KW - Down-Regulation -- drug effects KW - Drug Synergism KW - Female KW - Breast Neoplasms -- drug therapy KW - Receptor, ErbB-2 -- genetics KW - Ovarian Neoplasms -- metabolism KW - Apoptosis -- physiology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Breast Neoplasms -- metabolism KW - Antibodies, Monoclonal -- pharmacology KW - Tumor Necrosis Factor-alpha -- genetics KW - Ovarian Neoplasms -- drug therapy KW - Receptor, ErbB-2 -- physiology KW - Breast Neoplasms -- pathology KW - Ovarian Neoplasms -- pathology KW - Apoptosis -- drug effects KW - Membrane Glycoproteins -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Receptor, ErbB-2 -- biosynthesis KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70955800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Down-regulation+of+the+erbB-2+receptor+by+trastuzumab+%28herceptin%29+enhances+tumor+necrosis+factor-related+apoptosis-inducing+ligand-mediated+apoptosis+in+breast+and+ovarian+cancer+cell+lines+that+overexpress+erbB-2.&rft.au=Cuello%2C+M%3BEttenberg%2C+S+A%3BClark%2C+A+S%3BKeane%2C+M+M%3BPosner%2C+R+H%3BNau%2C+M+M%3BDennis%2C+P+A%3BLipkowitz%2C+S&rft.aulast=Cuello&rft.aufirst=M&rft.date=2001-06-15&rft.volume=61&rft.issue=12&rft.spage=4892&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of assessment methods for pesticide exposure in a case-control interview study. AN - 70947283; 11415959 AB - In epidemiologic studies, much of the variation in disease risk estimates associated with occupational pesticide exposure may be due to variation in exposure classification. The authors compared five different methods of using interview information to assess occupational pesticide exposure in a US-Canada case-control study of neuroblastoma (1992-1994). For each method, exposure assignment was compared with that of a reference method, and neuroblastoma effect estimates were calculated. Compared with the reference method, which included a complete review of occupation, industry, job tasks, and exposure-specific activities, the use of occupation-industry groups alone or in combination with general job task information diluted the exposed group by including individuals who were unlikely to have been truly exposed. The effect estimates representing associations between each exposure method and neuroblastoma were different enough to influence the study's conclusions, especially when the exposure was rare (for maternal occupational pesticide exposure, the odds ratio was 0.7 using the reference exposure assessment method and 3.2 using the occupation-industry group exposure assessment method). Exposure-specific questions about work activities can help investigators distinguish truly exposed individuals from those who report exposure but are unlikely to have been exposed above background levels and from those who have not been exposed but are misclassified as exposed because of their employment in an occupation-industry group determined a priori to be exposed. JF - American journal of epidemiology AU - Daniels, J L AU - Olshan, A F AU - Teschke, K AU - Hertz-Picciotto, I AU - Savitz, D A AU - Blatt, J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. daniels1@niehs.nih.gov Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 1227 EP - 1232 VL - 153 IS - 12 SN - 0002-9262, 0002-9262 KW - Pesticides KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Child KW - Predictive Value of Tests KW - Risk Assessment KW - Child, Preschool KW - Canada -- epidemiology KW - Infant KW - Logistic Models KW - Adult KW - Case-Control Studies KW - Interviews as Topic KW - United States -- epidemiology KW - Female KW - Male KW - Occupational Exposure KW - Paternal Exposure KW - Neuroblastoma -- epidemiology KW - Neuroblastoma -- chemically induced KW - Maternal Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70947283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Comparison+of+assessment+methods+for+pesticide+exposure+in+a+case-control+interview+study.&rft.au=Daniels%2C+J+L%3BOlshan%2C+A+F%3BTeschke%2C+K%3BHertz-Picciotto%2C+I%3BSavitz%2C+D+A%3BBlatt%2C+J&rft.aulast=Daniels&rft.aufirst=J&rft.date=2001-06-15&rft.volume=153&rft.issue=12&rft.spage=1227&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single vector containing modified cre recombinase and LOX recombination sequences for inducible tissue-specific amplification of gene expression. AN - 70925189; 11410679 AB - The selective alteration of the genome using Cre recombinase to target the rearrangement of genes flanked by LOX recognition sequences has required the use of two separate genetic constructs in trans, one containing cre and the other containing the gene of interest flanked by LOX sites. We have developed a strategy in which both the cre recombinase gene and LOX recombination sites may be cloned within a single vector in cis. This method uses a modified form of Cre (CREM) that contains alterations to the 5' region including the introduction of a Kozak consensus sequence and insertion of a functional intron. This system allows for the inducible, tissue-specific activation or inactivation of gene expression in a single vector and can be utilized for the 300-fold amplification of gene expression from a weak promoter. This approach can be applied to targeting strategies for generating genetically altered mice and gene therapy. JF - Nucleic acids research AU - Kaczmarczyk, S J AU - Green, J E AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - E56 VL - 29 IS - 12 KW - Viral Proteins KW - 0 KW - Cre recombinase KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - Animals KW - Transcription, Genetic -- genetics KW - Mice KW - Organ Specificity KW - Introns -- genetics KW - Prokaryotic Cells -- metabolism KW - Eukaryotic Cells -- metabolism KW - Genes, Reporter -- genetics KW - Consensus Sequence -- genetics KW - Cytomegalovirus -- genetics KW - Genetic Therapy -- methods KW - Promoter Regions, Genetic -- genetics KW - Frameshifting, Ribosomal -- genetics KW - Bacteriophage P1 -- enzymology KW - Mutagenesis, Insertional -- genetics KW - Integrases -- metabolism KW - Gene Targeting -- methods KW - Recombination, Genetic -- genetics KW - Integrases -- genetics KW - Gene Expression Regulation KW - Genetic Vectors -- genetics KW - Attachment Sites, Microbiological -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70925189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=A+single+vector+containing+modified+cre+recombinase+and+LOX+recombination+sequences+for+inducible+tissue-specific+amplification+of+gene+expression.&rft.au=Kaczmarczyk%2C+S+J%3BGreen%2C+J+E&rft.aulast=Kaczmarczyk&rft.aufirst=S&rft.date=2001-06-15&rft.volume=29&rft.issue=12&rft.spage=E56&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Prostate. 1997 Jul 1;32(2):129-39 [9215401] Nucleic Acids Res. 1997 May 1;25(9):1766-73 [9108159] Nucleic Acids Res. 1997 Nov 1;25(21):4323-30 [9336464] Methods. 1998 Apr;14(4):381-92 [9608509] Curr Biol. 1998 May 21;8(11):661-4 [9635194] Ann Med. 1998 Aug;30(4):390-6 [9783838] Ann N Y Acad Sci. 1998 Nov 17;859:160-74 [9928379] Dev Biol. 1999 Apr 15;208(2):281-92 [10191045] Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5037-42 [10220414] Nat Biotechnol. 1999 Nov;17(11):1091-6 [10545915] Oncogene. 2000 Feb 21;19(8):1020-7 [10713685] FEBS Lett. 2000 Mar 31;470(3):263-8 [10745079] Kidney Int. 2000 Apr;57(4):1299-306 [10760058] Hum Mol Genet. 2000 Apr 12;9(6):937-43 [10767317] Haematologica. 1999 Jun;84 Suppl EHA-4:64-6 [10907471] J Mol Biol. 1981 Aug 25;150(4):467-86 [6276557] Nucleic Acids Res. 1986 Mar 11;14(5):2287-300 [3457367] Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 [3313277] Gene. 1991 Dec 15;108(2):193-9 [1660837] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6232-6 [1631115] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6861-5 [1495975] Cell. 1993 Aug 13;74(3):505-14 [8348617] Methods Enzymol. 1993;225:890-900 [8231893] Science. 1994 Jul 1;265(5168):103-6 [8016642] Brain Pathol. 1994 Jan;4(1):3-20 [8025701] Science. 1995 Sep 8;269(5229):1427-9 [7660125] J Clin Invest. 1996 Aug 1;98(3):600-3 [8698848] Nucleic Acids Res. 1996 Oct 1;24(19):3875-7 [8871571] Cell. 1996 Dec 27;87(7):1317-26 [8980237] Mol Reprod Dev. 1997 Nov;48(3):324-31 [9322243] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung carcinoma in African Americans: a review of the current literature. AN - 70924431; 11413540 JF - Cancer AU - Stewart, J H AD - National Institutes of Health, National Cancer Institute, Surgery Branch-Thoracic Oncology Section, Bethesda, Maryland 20892-1502, USA. John_Stewart@nih.gov Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 2476 EP - 2482 VL - 91 IS - 12 SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Occupational Exposure KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Smoking -- epidemiology KW - Lung Neoplasms -- epidemiology KW - Lung Neoplasms -- therapy KW - Lung Neoplasms -- genetics KW - African Americans KW - Lung Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70924431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Lung+carcinoma+in+African+Americans%3A+a+review+of+the+current+literature.&rft.au=Stewart%2C+J+H&rft.aulast=Stewart&rft.aufirst=J&rft.date=2001-06-15&rft.volume=91&rft.issue=12&rft.spage=2476&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive activation of A(3) adenosine receptors by site-directed mutagenesis. AN - 70911451; 11396942 AB - The objective of this study was to create constitutively active mutant human A(3) adenosine receptors (ARs) using single amino acid replacements, based on findings from other G protein-coupled receptors. A(3) ARs mutated in transmembrane helical domains (TMs) 1, 3, 6, and 7 were expressed in COS-7 cells and subjected to agonist radioligand binding and phospholipase C (PLC) and adenylyl cyclase (AC) assays. Three mutant receptors, A229E in TM6 and R108A and R108K in the DRY motif of TM3, were found to be constitutively active in both functional assays. The potency of the A(3) agonist Cl-IB-MECA (1-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) in PLC activation was enhanced by at least an order of magnitude over wild type (EC(50) 951 nM) in R108A and A229E mutant receptors. Cl-IB-MECA was much less potent (>10-fold) in C88F, Y109F, and Y282F and mutants or inactive following double mutation of the DRY motif. The degree of constitutive activation was more pronounced for the AC signaling pathway than for the PLC signaling pathway. The results indicated that specific locations within the TMs proximal to the cytosolic region were responsible for constraining the receptor in a G protein-uncoupled conformation. Copyright 2001 Academic Press. JF - Biochemical and biophysical research communications AU - Chen, A AU - Gao, Z G AU - Barak, D AU - Liang, B T AU - Jacobson, K A AD - Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 596 EP - 601 VL - 284 IS - 3 SN - 0006-291X, 0006-291X KW - Phosphatidylinositols KW - 0 KW - Receptor, Adenosine A3 KW - Receptors, Purinergic P1 KW - Cyclic AMP KW - E0399OZS9N KW - Adenosine KW - K72T3FS567 KW - 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide KW - Z07JR07J6C KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Phosphatidylinositols -- metabolism KW - Cyclic AMP -- biosynthesis KW - Animals KW - Adenosine -- pharmacology KW - COS Cells KW - Transfection KW - Humans KW - Adenosine -- analogs & derivatives KW - Point Mutation KW - Adenosine -- metabolism KW - Receptors, Purinergic P1 -- genetics KW - Receptors, Purinergic P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70911451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Constitutive+activation+of+A%283%29+adenosine+receptors+by+site-directed+mutagenesis.&rft.au=Chen%2C+A%3BGao%2C+Z+G%3BBarak%2C+D%3BLiang%2C+B+T%3BJacobson%2C+K+A&rft.aulast=Chen&rft.aufirst=A&rft.date=2001-06-15&rft.volume=284&rft.issue=3&rft.spage=596&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1990 Oct 5;250(4977):123-5 [2218504] J Biol Chem. 1992 Jan 25;267(3):1430-3 [1346134] J Biol Chem. 1993 Mar 5;268(7):4625-36 [8095262] Eur J Pharmacol. 1994 Sep 22;263(1-2):59-67 [7821362] J Biol Chem. 1995 Feb 17;270(7):3141-6 [7852396] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] J Biol Chem. 1995 Jul 14;270(28):16895-902 [7622506] Basic Res Cardiol. 1995 Mar-Apr;90(2):85-8 [7646421] Mol Pharmacol. 1996 Jan;49(1):112-22 [8569696] J Clin Invest. 1996 Oct 15;98(8):1773-9 [8878427] Blood. 1996 Nov 1;88(9):3569-74 [8896425] J Biol Chem. 1996 Nov 8;271(45):28318-23 [8910453] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):808-13 [9023338] J Biol Chem. 1998 Feb 6;273(6):3401-7 [9452461] J Biol Chem. 1998 Apr 3;273(14):7900-5 [9525885] Mol Pharmacol. 1998 May;53(5):886-93 [9584215] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6995-9 [9618527] Trends Pharmacol Sci. 1998 May;19(5):177-83 [9652190] J Pharmacol Exp Ther. 1998 Jul;286(1):85-90 [9655845] Mol Neurobiol. 1998 Winter;17(1-3):109-35 [9887449] J Biol Chem. 1999 Jun 25;274(26):18574-81 [10373467] Eur Urol. 1999;36 Suppl 1:11-6 [10393467] Biochem J. 1988 Jun 1;252(2):583-93 [2843174] Methods Enzymol. 1987;152:684-704 [3657593] Biochem J. 1983 May 15;212(2):473-82 [6309146] J Biol Chem. 1980 Aug 10;255(15):7108-17 [6248546] Anal Biochem. 1976 May 7;72:248-54 [942051] Nature. 2000 Dec 14;408(6814):860-4 [11130725] FASEB J. 2000 Jul;14(10):1423-31 [10877835] Mol Pharmacol. 2000 May;57(5):890-8 [10779371] Endocr Rev. 2000 Feb;21(1):90-113 [10696571] Mol Pharmacol. 2000 Feb;57(2):219-31 [10648631] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7321-5 [2552439] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Ataxia telangiectasia gene product is required for oxidative stress-induced G1 and G2 checkpoint function in human fibroblasts. AN - 70909973; 11290740 AB - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by neuronal degeneration accompanied by ataxia, telangiectasias, acute cancer predisposition, and sensitivity to ionizing radiation (IR). Cells from individuals with AT show unusual sensitivity to IR, severely attenuated cell cycle checkpoint functions, and poor p53 induction in response to IR compared with normal human fibroblasts (NHFs). The gene mutated in AT (ATM) has been cloned, and its product, pATM, has IR-inducible kinase activity. The AT phenotype has been suggested to be a consequence, at least in part, of an inability to respond appropriately to oxidative damage. To test this hypothesis, we examined the ability of NHFs and AT dermal fibroblasts to respond to t-butyl hydroperoxide and IR treatment. AT fibroblasts exhibit, in comparison to NHFs, increased sensitivity to the toxicity of t-butyl hydroperoxide, as measured by colony-forming efficiency assays. Unlike NHFs, AT fibroblasts fail to show G(1) and G(2) phase checkpoint functions or to induce p53 in response to t-butyl hydroperoxide. Treatment of NHFs with t-butyl hydroperoxide activates pATM-associated kinase activity. Our results indicate that pATM is involved in responding to certain aspects of oxidative damage and in signaling this information to downstream effectors of the cell cycle checkpoint functions. Our data further suggest that some of the pathologies seen in AT could arise as a consequence of an inability to respond normally to oxidative damage. JF - The Journal of biological chemistry AU - Shackelford, R E AU - Innes, C L AU - Sieber, S O AU - Heinloth, A N AU - Leadon, S A AU - Paules, R S AD - Growth Control and Cancer Group, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 21951 EP - 21959 VL - 276 IS - 24 SN - 0021-9258, 0021-9258 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - Recombinant Proteins KW - Tumor Suppressor Proteins KW - tert-Butylhydroperoxide KW - 955VYL842B KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Humans KW - Cloning, Molecular KW - G2 Phase -- physiology KW - Cell Survival -- drug effects KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - tert-Butylhydroperoxide -- pharmacology KW - Adolescent KW - Cell Line KW - Female KW - G1 Phase -- physiology KW - Ataxia Telangiectasia -- genetics KW - Oxidative Stress -- physiology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Fibroblasts -- pathology KW - Protein-Serine-Threonine Kinases -- deficiency KW - Cell Cycle -- physiology KW - Protein-Serine-Threonine Kinases -- genetics KW - Fibroblasts -- cytology KW - Ataxia Telangiectasia -- pathology KW - Fibroblasts -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70909973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+Ataxia+telangiectasia+gene+product+is+required+for+oxidative+stress-induced+G1+and+G2+checkpoint+function+in+human+fibroblasts.&rft.au=Shackelford%2C+R+E%3BInnes%2C+C+L%3BSieber%2C+S+O%3BHeinloth%2C+A+N%3BLeadon%2C+S+A%3BPaules%2C+R+S&rft.aulast=Shackelford&rft.aufirst=R&rft.date=2001-06-15&rft.volume=276&rft.issue=24&rft.spage=21951&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stat6 is necessary and sufficient for IL-4's role in Th2 differentiation and cell expansion. AN - 70898756; 11390477 AB - IL-4 plays a critical role in the differentiation of TCR-stimulated naive CD4 T cells to the Th2 phenotype. In response to IL-4, the IL-4R activates a set of phosphotyrosine binding domain-containing proteins, including insulin receptor substrate 1/2, Shc, and IL-4R interacting protein, as well as Stat6. Stat6 has been shown to be required for Th2 differentiation. To determine the roles of the phosphotyrosine binding adaptors in Th2 differentiation, we prepared a retrovirus containing a mutant of the human (h)IL-4R alpha-chain, Y497F, which is unable to recruit these adaptors. The mutant hIL-4Ralpha, as well as the wild-type (WT) hIL-4Ralpha, was introduced into naive CD4 T cells. Upon hIL-4 stimulation, Y497F worked as well as the WT hIL-4Ralpha in driving Th2 differentiation, as measured by Gata3 up-regulation and IL-4 production. Furthermore, IL-4-driven cell expansion was also normal in the cells infected with Y497F, although cells infected with Y497F were not capable of phosphorylating insulin receptor substrate 2. These results suggest that the signal pathway mediated by Y497 is dispensable for both IL-4-driven Th2 differentiation and cell expansion. Both WT and Y497F hIL-4Ralpha lose the ability to drive Th2 differentiation and cell expansion in Stat6-knockout CD4 T cells. A constitutively activated form of Stat6 introduced into CD4 T cells resulted in both Th2 differentiation and enhanced cell expansion. Thus, activated Stat6 is necessary and sufficient to mediate both IL-4-driven Th2 differentiation and cell expansion in CD4 T cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Zhu, J AU - Guo, L AU - Watson, C J AU - Hu-Li, J AU - Paul, W E AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 7276 EP - 7281 VL - 166 IS - 12 SN - 0022-1767, 0022-1767 KW - Antigens, CD3 KW - 0 KW - IRS2 protein, human KW - Immune Sera KW - Insulin Receptor Substrate Proteins KW - Intracellular Signaling Peptides and Proteins KW - Irs2 protein, mouse KW - Phosphoproteins KW - STAT6 Transcription Factor KW - Stat6 protein, mouse KW - Trans-Activators KW - Interleukin-4 KW - 207137-56-2 KW - Tyrosine KW - 42HK56048U KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - CD4-Positive T-Lymphocytes -- cytology KW - Coculture Techniques KW - Genetic Vectors -- immunology KW - CD4-Positive T-Lymphocytes -- immunology KW - Cell Differentiation -- genetics KW - Mice KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Cell Differentiation -- immunology KW - Mutagenesis, Site-Directed KW - Antigens, CD3 -- immunology KW - CD4-Positive T-Lymphocytes -- metabolism KW - Phosphorylation KW - Cells, Cultured KW - Genetic Vectors -- physiology KW - Tyrosine -- genetics KW - Tyrosine -- metabolism KW - Immune Sera -- pharmacology KW - Phosphoproteins -- metabolism KW - Th2 Cells -- metabolism KW - Trans-Activators -- metabolism KW - Trans-Activators -- deficiency KW - Lymphocyte Activation -- genetics KW - Th2 Cells -- cytology KW - Trans-Activators -- genetics KW - Lymphocyte Activation -- immunology KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - Trans-Activators -- physiology KW - Th2 Cells -- immunology KW - Interleukin-4 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70898756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Stat6+is+necessary+and+sufficient+for+IL-4%27s+role+in+Th2+differentiation+and+cell+expansion.&rft.au=Zhu%2C+J%3BGuo%2C+L%3BWatson%2C+C+J%3BHu-Li%2C+J%3BPaul%2C+W+E&rft.aulast=Zhu&rft.aufirst=J&rft.date=2001-06-15&rft.volume=166&rft.issue=12&rft.spage=7276&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation of chemokine gene expression by 15-deoxy-delta 12,14 prostaglandin J2. AN - 70890083; 11390455 AB - Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), such as 15-deoxy-Delta(12,14)PGJ2 (15d-PGJ2) have been proposed as a new class of antiinflammatory compounds with possible clinical applications. As there is some controversy over the inhibitory effects of 15d-PGJ2 on chemokine gene expression, we investigated whether 15d-PGJ2 itself affected chemokine gene expression in human monocytes/macrophages and two monocytic cell lines. Here we demonstrate that the 15d-PGJ2 can induce IL-8 gene expression. In contrast, monocyte chemoattractant protein-1 gene expression was suppressed by 15d-PGJ2, while the expression of RANTES was unaltered. Furthermore, concomitant treatment of monocytes/macrophages with 15d-PGJ2 (2.5 x 10(-6) M) potentiated LPS-induced gene expression of IL-8 mRNA, but suppressed PMA-induction of IL-8 mRNA. In addition, treatment of U937 and THP-1 cells with 15d-PGJ2 also resulted in induction of IL-8 gene expression. Further studies demonstrated that 15d-PGJ2 regulated IL-8 gene expression via a ligand-specific and PPARgamma-dependent pathway. Our observations revealed a previous unappreciated function and mechanism of 15d-PGJ2-mediated regulation of cytokine gene expression in monocytes/macrophages. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Zhang, X AU - Wang, J M AU - Gong, W H AU - Mukaida, N AU - Young, H A AD - Laboratory of Experimental Immunology, and Laboratory of Molecular Immunoregulation, Division of Basic Science, National Cancer Institute-Frederick Cancer Research Development Center, National Institute of Health, Frederick, MD 21702, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 7104 EP - 7111 VL - 166 IS - 12 SN - 0022-1767, 0022-1767 KW - 15-deoxy-delta(12,14)-prostaglandin J2 KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - COUP Transcription Factors KW - Chemokine CCL2 KW - Chemokine CCL5 KW - Chemokines KW - DNA-Binding Proteins KW - Interleukin-8 KW - Ligands KW - Lipopolysaccharides KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Steroid KW - Transcription Factors KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Prostaglandin D2 KW - RXY07S6CZ2 KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Chemokine CCL5 -- biosynthesis KW - Promoter Regions, Genetic -- immunology KW - Transcription Factors -- metabolism KW - Neutrophils -- immunology KW - Humans KW - Lipopolysaccharides -- pharmacology KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Promoter Regions, Genetic -- drug effects KW - Chemotaxis, Leukocyte -- immunology KW - Chemokine CCL2 -- biosynthesis KW - Cell-Free System -- physiology KW - Transcription Factors -- physiology KW - Peroxisomes -- metabolism KW - Interleukin-8 -- antagonists & inhibitors KW - Receptors, Cytoplasmic and Nuclear -- biosynthesis KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Interleukin-8 -- biosynthesis KW - Transfection KW - Cells, Cultured KW - Monocytes -- immunology KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Monocytes -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Interleukin-8 -- genetics KW - DNA-Binding Proteins -- physiology KW - Prostaglandin D2 -- pharmacology KW - Chemokines -- genetics KW - Prostaglandin D2 -- metabolism KW - Prostaglandin D2 -- analogs & derivatives KW - Chemokines -- biosynthesis KW - Gene Expression Regulation -- drug effects KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70890083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Differential+regulation+of+chemokine+gene+expression+by+15-deoxy-delta+12%2C14+prostaglandin+J2.&rft.au=Zhang%2C+X%3BWang%2C+J+M%3BGong%2C+W+H%3BMukaida%2C+N%3BYoung%2C+H+A&rft.aulast=Zhang&rft.aufirst=X&rft.date=2001-06-15&rft.volume=166&rft.issue=12&rft.spage=7104&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunopathogenesis of human immunodeficiency virus: implications for immune-based therapies. AN - 70855824; 11360217 AB - Human immunodeficiency virus (HIV) infection leads to a state of CD4 lymphopenia and generalized immune activation with subsequent development of opportunistic infections and neoplasms. The use of highly active antiretroviral treatment has dramatically improved the clinical outcome for HIV-infected patients, but the associated cost and toxicity and the eventual development of drug resistance have underscored the need for additional therapeutic strategies. Immune-based therapies, such as treatment with cytokines or immunosuppressants, adoptive immunotherapy, and therapeutic immunizations, are being intensely investigated as potential supplements to antiretroviral therapy. Although much data have been generated as a result of these efforts, to date there has been little evidence of the clinical efficacy of these strategies. Randomized clinical studies remain critical in evaluating the clinical significance and the role of immune-based therapies in the therapeutic armamentarium against HIV. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Sereti, I AU - Lane, H C AD - Cellular and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 1738 EP - 1755 VL - 32 IS - 12 SN - 1058-4838, 1058-4838 KW - Index Medicus KW - Acute Disease KW - CD4-Positive T-Lymphocytes -- cytology KW - Animals KW - Virus Latency KW - Humans KW - Antiretroviral Therapy, Highly Active KW - CD4-Positive T-Lymphocytes -- immunology KW - Disease Reservoirs KW - Chronic Disease KW - Immune System KW - HIV-1 -- genetics KW - HIV-1 -- immunology KW - HIV Infections -- virology KW - HIV Infections -- therapy KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - HIV-1 -- physiology KW - Immunotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70855824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Immunopathogenesis+of+human+immunodeficiency+virus%3A+implications+for+immune-based+therapies.&rft.au=Sereti%2C+I%3BLane%2C+H+C&rft.aulast=Sereti&rft.aufirst=I&rft.date=2001-06-15&rft.volume=32&rft.issue=12&rft.spage=1738&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of new anti-CD30 scFvs from DNA-immunized mice by phage display and biologic activity of recombinant immunotoxins produced by fusion with truncated pseudomonas exotoxin. AN - 70841812; 11351308 AB - To target CD30 on Hodgkin's disease and anaplastic large-cell lymphoma, anti-CD30 single-chain antibodies were obtained by DNA immunization of mice with the complete human CD30 cDNA. Spleens were isolated from mice with high anti-CD30 titer, and the RNA was used for the production of an scFv-displaying phage library. Specific phages were enriched by 3 rounds of panning on soluble CD30 or CD30+ K562 cells. Recombinant immunotoxins (rITs) were made from 3 ELISA-positive scFv phages by fusion to a 38 kDa truncated mutant of Pseudomonas exotoxin (PE38) with or without a KDEL mutant sequence at the C terminus. In vitro cytotoxicity of purified anti-CD30 rITs was measured on CD30-transfected A431 cells. IC50 values ranged from 3 to 7 ng/ml (50-110 pM) for PE38 rITs and 0.1 ng/ml (2 pM) for the PE38-KDEL IT on A431-CD30 cells. The parental A431 cells were resistant, indicating that the cytotoxicity was specific and CD30-mediated. rITs were tested for anti-tumor activity in a nude mouse model. A431-CD30 cells were injected s.c. on day 0; then, mice bearing measurable tumors were treated beginning on day 4 with 3 alternate daily doses i.v. Anti-tumor activity was dose-dependent and not found when irrelevant ITs were administered or when CD30- tumors were treated. Our data show that DNA immunization and antibody phage display may be useful in producing new rITs against hematologic malignancies. Published 2001 Wiley-Liss, Inc. JF - International journal of cancer AU - Rozemuller, H AU - Chowdhury, P S AU - Pastan, I AU - Kreitman, R J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/06/15/ PY - 2001 DA - 2001 Jun 15 SP - 861 EP - 870 VL - 92 IS - 6 SN - 0020-7136, 0020-7136 KW - Antigens, CD30 KW - 0 KW - Bacterial Toxins KW - Cancer Vaccines KW - Codon KW - DNA, Complementary KW - Exotoxins KW - Immunoglobulin Fragments KW - Peptide Library KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Virulence Factors KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Humans KW - Surface Plasmon Resonance KW - Mice, Nude KW - Mice, Inbred BALB C KW - Models, Biological KW - Tumor Cells, Cultured KW - RNA -- metabolism KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Inhibitory Concentration 50 KW - Sequence Homology, Amino Acid KW - Time Factors KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Mice KW - Amino Acid Sequence KW - RNA, Messenger -- metabolism KW - Transfection KW - Kinetics KW - DNA, Complementary -- metabolism KW - Mice, Inbred C57BL KW - Cell Line KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Proteins -- metabolism KW - DNA -- metabolism KW - Immunoglobulin Fragments -- metabolism KW - Exotoxins -- metabolism KW - Antigens, CD30 -- chemistry KW - Antigens, CD30 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70841812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Isolation+of+new+anti-CD30+scFvs+from+DNA-immunized+mice+by+phage+display+and+biologic+activity+of+recombinant+immunotoxins+produced+by+fusion+with+truncated+pseudomonas+exotoxin.&rft.au=Rozemuller%2C+H%3BChowdhury%2C+P+S%3BPastan%2C+I%3BKreitman%2C+R+J&rft.aulast=Rozemuller&rft.aufirst=H&rft.date=2001-06-15&rft.volume=92&rft.issue=6&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cost of immunization with a locally produced, oral cholera vaccine in Viet Nam AN - 17906059; 5142455 AB - Policy decisions regarding whether to incorporate new vaccines into routine public health practice in developing countries will depend in part on the costs of vaccine purchase and of vaccine delivery. In March, 1997, a large-scale effectiveness trial of a locally produced, orally administered bivalent vaccine against Vibrio cholerae 01 and 0139 began in Viet Nam. Empirical data obtained from the trial was used to determine the costs of the immunization campaign from the government perspective. The study population, including the children less than one year of age and pregnant women who were ineligible for immunization, was 353926. A total of 289041 persons received two doses of vaccine, and 13340 persons received one dose of vaccine. Two-dose vaccine coverage was 83.4%. The total cost of vaccine delivery during the immunization campaign was $66527. The cost of each dose of vaccine was $0.31. Therefore, the total cost of the immunization campaign was $0.44 per dose administered, and $0.91 per fully immunized person. Attempts to reduce the cost per dose of vaccine (e.g. the use of a monovalent vaccine against serogroup 01) are likely to have a large impact on the cost of future similar immunization campaigns. JF - Vaccine AU - Naficy, AB AU - Trach, D D AU - Ke, N T AU - Chuc, NTK AU - Sorkin, A AU - Rao, M R AU - Sy, TH AU - Thiem, V D AU - Canh, D G AU - Mahoney, R T AU - Holmgren, J AU - Ivanoff, B AU - Clemens, J D AD - Epidemiology Branch, National Institute of Child Health and Human Development, 6100 Executive Blvd., Suite 7B03, Rockville, MD 20852, USA, an38i@nih.gov Y1 - 2001/06/14/ PY - 2001 DA - 2001 Jun 14 SP - 3720 EP - 3725 VL - 19 IS - 27 SN - 0264-410X, 0264-410X KW - man KW - Vibrio cholerae KW - Vietnam KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Cost-benefit analysis KW - Cholera KW - Vaccines KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17906059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Cost+of+immunization+with+a+locally+produced%2C+oral+cholera+vaccine+in+Viet+Nam&rft.au=Naficy%2C+AB%3BTrach%2C+D+D%3BKe%2C+N+T%3BChuc%2C+NTK%3BSorkin%2C+A%3BRao%2C+M+R%3BSy%2C+TH%3BThiem%2C+V+D%3BCanh%2C+D+G%3BMahoney%2C+R+T%3BHolmgren%2C+J%3BIvanoff%2C+B%3BClemens%2C+J+D&rft.aulast=Naficy&rft.aufirst=AB&rft.date=2001-06-14&rft.volume=19&rft.issue=27&rft.spage=3720&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae; Cholera; Vaccines; Cost-benefit analysis ER - TY - JOUR T1 - Mutual antagonism of calcium entry by capacitative and arachidonic acid-mediated calcium entry pathways. AN - 70907708; 11274150 AB - In nonexcitable cells, the predominant mechanism for regulated entry of Ca(2+) is capacitative calcium entry, whereby depletion of intracellular Ca(2+) stores signals the activation of plasma membrane calcium channels. A number of other regulated Ca(2+) entry pathways occur in specific cell types, however, and it is not know to what degree the different pathways interact when present in the same cell. In this study, we have examined the interaction between capacitative calcium entry and arachidonic acid-activated calcium entry, which co-exist in HEK293 cells. These two pathways exhibit mutual antagonism. That is, capacitative calcium entry is potently inhibited by arachidonic acid, and arachidonic acid-activated entry is inhibited by the pre-activation of capacitative calcium entry with thapsigargin. In the latter case, the inhibition does not seem to result from a direct action of thapsigargin, inhibition of endoplasmic reticulum Ca(2+) pumps, depletion of Ca(2+) stores, or entry of Ca(2+) through capacitative calcium entry channels. Rather, it seems that a discrete step in the pathway signaling capacitative calcium entry interacts with and inhibits the arachidonic acid pathway. The findings reveal a novel process of mutual antagonism between two distinct calcium entry pathways. This mutual antagonism may provide an important protective mechanism for the cell, guarding against toxic Ca(2+) overload. JF - The Journal of biological chemistry AU - Luo, D AU - Broad, L M AU - Bird, G S AU - Putney, J W AD - Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/06/08/ PY - 2001 DA - 2001 Jun 08 SP - 20186 EP - 20189 VL - 276 IS - 23 SN - 0021-9258, 0021-9258 KW - Calcium Channel Blockers KW - 0 KW - Arachidonic Acid KW - 27YG812J1I KW - Thapsigargin KW - 67526-95-8 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Thapsigargin -- pharmacology KW - Calcium Channel Blockers -- pharmacology KW - Humans KW - Cell Line KW - Calcium -- metabolism KW - Calcium -- antagonists & inhibitors KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70907708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Mutual+antagonism+of+calcium+entry+by+capacitative+and+arachidonic+acid-mediated+calcium+entry+pathways.&rft.au=Luo%2C+D%3BBroad%2C+L+M%3BBird%2C+G+S%3BPutney%2C+J+W&rft.aulast=Luo&rft.aufirst=D&rft.date=2001-06-08&rft.volume=276&rft.issue=23&rft.spage=20186&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional characterization of transforming growth factor beta signaling in Smad2- and Smad3-deficient fibroblasts. AN - 70904580; 11262418 AB - A prominent pathway of transforming growth factor (TGF)-beta signaling involves receptor-dependent phosphorylation of Smad2 and Smad3, which then translocate to the nucleus to activate transcription of target genes. To investigate the relative importance of these two Smad proteins in TGF-beta1 signal transduction, we have utilized a loss of function approach, based on analysis of the effects of TGF-beta1 on fibroblasts derived from mouse embryos deficient in Smad2 (S2KO) or Smad3 (S3KO). TGF-beta1 caused 50% inhibition of cellular proliferation in wild-type fibroblasts as assessed by [(3)H]thymidine incorporation, whereas the growth of S2KO or S3KO cells was only weakly inhibited by TGF-beta1. Lack of Smad2 or Smad3 expression did not affect TGF-beta1-induced fibronectin synthesis but resulted in markedly suppressed induction of plasminogen activator inhibitor-1 by TGF-beta1. Moreover, TGF-beta1-mediated induction of matrix metalloproteinase-2 was selectively dependent on Smad2, whereas induction of c-fos, Smad7, and TGF-beta1 autoinduction relied on expression of Smad3. Investigation of transcriptional activation of TGF-beta-sensitive reporter genes in the different fibroblasts showed that activation of the (Smad binding element)(4)-Lux reporter by TGF-beta1 was dependent on expression of Smad3, but not Smad2, whereas activation of the activin response element-Lux reporter was strongly suppressed in S2KO fibroblasts but, on the contrary, enhanced in S3KO cells. Our findings indicate specific roles for Smad2 and Smad3 in TGF-beta1 signaling. JF - The Journal of biological chemistry AU - Piek, E AU - Ju, W J AU - Heyer, J AU - Escalante-Alcalde, D AU - Stewart, C L AU - Weinstein, M AU - Deng, C AU - Kucherlapati, R AU - Bottinger, E P AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. pieke@mail.nih.gov Y1 - 2001/06/08/ PY - 2001 DA - 2001 Jun 08 SP - 19945 EP - 19953 VL - 276 IS - 23 SN - 0021-9258, 0021-9258 KW - Cdkn1a protein, mouse KW - 0 KW - Cdkn2b protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor beta KW - Tumor Suppressor Proteins KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Transcription, Genetic KW - Fibroblasts -- cytology KW - Mice KW - Fibroblasts -- metabolism KW - Genes, Immediate-Early KW - Mice, Knockout KW - Genes, Reporter KW - Cyclins -- metabolism KW - Genes, fos KW - Cell Division KW - Transforming Growth Factor beta -- biosynthesis KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70904580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+characterization+of+transforming+growth+factor+beta+signaling+in+Smad2-+and+Smad3-deficient+fibroblasts.&rft.au=Piek%2C+E%3BJu%2C+W+J%3BHeyer%2C+J%3BEscalante-Alcalde%2C+D%3BStewart%2C+C+L%3BWeinstein%2C+M%3BDeng%2C+C%3BKucherlapati%2C+R%3BBottinger%2C+E+P%3BRoberts%2C+A+B&rft.aulast=Piek&rft.aufirst=E&rft.date=2001-06-08&rft.volume=276&rft.issue=23&rft.spage=19945&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Domain 1.1 of the Subunit of Escherichia coli RNA Polymerase Modulates the Formation of Stable Polymerase-Promoter Complexes AN - 17895727; 5131704 AB - The sigma 70 ( super(70)) subunit of Escherichia coli RNA polymerase specifies transcription from promoters that are responsible for basal gene expression during vegetative growth. When super(70) is present within polymerase holoenzyme, two of its domains, 2.4 and 4.2, interact with sequences within the 10 and 35 regions, respectively, of promoter DNA. However, in free super(70), DNA binding is prevented by domain 1.1, the N-terminal domain of the protein. Previous work has demonstrated that the presence of domain 1.1 is required for efficient transcription initiation at the lambda promoter P sub(R). To investigate whether this is a general property of domain 1.1, we have used five promoters to compare polymerases with and without domain 1.1 in in vitro transcription assays, and in assays assessing the formation and decay of stable, pretranscription complexes. We find that the absence of domain 1.1 does not render the polymerase defective at all of these promoters. Depending on the promoter, the absence of domain 1.1 can promote or inhibit transcription initiation by affecting the formation of stable pretranscription complexes. However, domain 1.1 does not affect the stability of these complexes once they are formed. For polymerases containing domain 1.1, the efficiency of stable complex formation correlates with how well the 10 and 35 regions of a promoter match the ideal super(70) recognition sequences. However, when domain 1.1 is absent, having this match becomes less important in determining how efficiently stable complexes are made. We suggest that domain 1.1 influences initiation by constraining polymerase to assess a promoter primarily by the fitness of its 10 and 35 regions to the canonical sequences. Copyright 2001 Academic Press JF - Journal of Molecular Biology AU - Vuthoori, S AU - Bowers, C W AU - Mccracken, A AU - Dombroski, A J AU - Hinton, D M AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room 2A-13, Bethesda, MD, 20892, USA Y1 - 2001/06/08/ PY - 2001 DA - 2001 Jun 08 SP - 571 EP - 582 PB - Academic Press VL - 309 IS - 3 SN - 0022-2836, 0022-2836 KW - sigma 70 factor KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - s70 factor KW - ^s70 factor KW - Promoters KW - DNA-directed RNA polymerase KW - Escherichia coli KW - N-Terminus KW - Transcription initiation KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Domain+1.1+of+the+Subunit+of+Escherichia+coli+RNA+Polymerase+Modulates+the+Formation+of+Stable+Polymerase-Promoter+Complexes&rft.au=Vuthoori%2C+S%3BBowers%2C+C+W%3BMccracken%2C+A%3BDombroski%2C+A+J%3BHinton%2C+D+M&rft.aulast=Vuthoori&rft.aufirst=S&rft.date=2001-06-08&rft.volume=309&rft.issue=3&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2001.4690 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed RNA polymerase; Transcription initiation; Promoters; N-Terminus DO - http://dx.doi.org/10.1006/jmbi.2001.4690 ER - TY - JOUR T1 - Novel human p53 mutations that are toxic to yeast can enhance transactivation of specific promoters and reactivate tumor p53 mutants. AN - 70962558; 11423991 AB - Since highly expressed human p53 can inhibit human and yeast cell growth, we predicted that p53 mutants could be generated with increased growth inhibition of the yeast Saccharomyces cerevisiae and that these would be useful for characterizing p53 functions and tumor p53 mutants. A random mutagenesis screen led to the isolation of mutations in the DNA binding domain that result in p53 being lethal even at moderate expression levels in yeast. Three independent mutants had an alanine change at the evolutionary invariant V122 in the L1 loop. The other toxic mutations affected codons 277 (C277R, C277W) and 279 (G279R). This latter amino acid change was also reported in tumors, while all the other mutations are novel. A recently developed rheostatable GALI promoter system that provides graded increases in expression of p53 was used to examine the transactivation function of the toxic mutations when expression was greatly reduced and cells were viable. At low expression levels the toxic mutants lacked transactivation from a 3xRGC responsive element (RE). Surprisingly some exhibited enhanced transactivation with p21 and bax REs. The V122A mutant was able to re-activate transactivation of various p53 tumor mutants and retained growth inhibition when co-expressed with dominant-negative tumor mutations. Upon expression in human Saos-2 cells the V122A p53 mutant caused growth suppression, was capable of transactivation and exhibited higher than wild type activity with the bax promoter in luciferase assays. A non-functional p53 tumor mutant was partially reactivated by V122A for both transactivation and growth suppression. Thus, the screen for toxic p53 mutants in yeast can identify novel p53 variants that may be useful in dissecting p53 regulated cellular responses and in developing p53-based cancer therapies. JF - Oncogene AU - Inga, A AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, PO Box 12233, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/06/07/ PY - 2001 DA - 2001 Jun 07 SP - 3409 EP - 3419 VL - 20 IS - 26 SN - 0950-9232, 0950-9232 KW - BAX protein, human KW - 0 KW - DNA, Fungal KW - Fungal Proteins KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Fusion Proteins KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - DNA -- metabolism KW - Humans KW - Fungal Proteins -- genetics KW - Mutation, Missense KW - Binding Sites KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Regulatory Sequences, Nucleic Acid KW - Fungal Proteins -- metabolism KW - Tumor Cells, Cultured KW - Genes, Dominant KW - Transformation, Genetic KW - Neoplasm Proteins -- genetics KW - Genetic Complementation Test KW - Proto-Oncogene Proteins -- genetics KW - Protein Structure, Tertiary KW - Neoplasm Proteins -- metabolism KW - DNA, Fungal -- metabolism KW - Genes, Lethal KW - Amino Acid Substitution KW - Tumor Suppressor Protein p53 -- physiology KW - Saccharomyces cerevisiae -- metabolism KW - Genes, p53 KW - Saccharomyces cerevisiae -- growth & development KW - Osteosarcoma -- pathology KW - Transcriptional Activation -- genetics KW - Osteosarcoma -- genetics KW - Promoter Regions, Genetic -- genetics KW - Bone Neoplasms -- pathology KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- genetics KW - Bone Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70962558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Novel+human+p53+mutations+that+are+toxic+to+yeast+can+enhance+transactivation+of+specific+promoters+and+reactivate+tumor+p53+mutants.&rft.au=Inga%2C+A%3BResnick%2C+M+A&rft.aulast=Inga&rft.aufirst=A&rft.date=2001-06-07&rft.volume=20&rft.issue=26&rft.spage=3409&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An optimized protein kinase C activating diacylglycerol combining high binding affinity (Ki) with reduced lipophilicity (log P). AN - 70884365; 11384235 AB - A small, focused combinatorial library encompassing all possible permutations of acyl branched alkyl chains-small and large, saturated and unsaturated-was generated from the active diacylglycerol enantiomer (S-DAG) to help identify the analogue with the highest binding affinity (lowest Ki) for protein kinase C (PK-C) combined with the minimum lipophilicity (log P). The selected ligand (3B) activated PK-C more effectively than sn-1,2-dioctanoylglycerol (diC8) despite being 1.4 log units more hydrophilic. Compound 3B indeed represents the most potent, hydrophilic DAG ligand to date. With the help of a green fluorescent protein (GFP)-tagged PK-Calpha, 3B was able to translocate the full length protein to the membrane with an optimal dose of 100 microM in CHO-K1 cells, while diC8 failed to achieve translocation even at doses 3-fold higher. Molecular modeling of 3B into an empty C1b domain of PK-Cdelta clearly showed the existence of a preferred binding orientation. In addition, molecular dynamic simulations suggest that binding discrimination could result from a favorable van der Waals (VDW) interaction between the large, branched sn-1 acyl group of 3B and the aromatic rings of Trp252 (PK-Cdelta) or Tyr252 (PK-Calpha). The DAG analogue of 3B in which the acyl groups are reversed (2C) showed a decrease in binding affinity reflecting the capacity of PK-C to effectively discriminate between alternative orientations of the acyl chains. JF - Journal of medicinal chemistry AU - Nacro, K AU - Sigano, D M AU - Yan, S AU - Nicklaus, M C AU - Pearce, L L AU - Lewin, N E AU - Garfield, S H AU - Blumberg, P M AU - Marquez, V E AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2001/06/07/ PY - 2001 DA - 2001 Jun 07 SP - 1892 EP - 1904 VL - 44 IS - 12 SN - 0022-2623, 0022-2623 KW - Diglycerides KW - 0 KW - Recombinant Fusion Proteins KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Tyrosine KW - 42HK56048U KW - Tryptophan KW - 8DUH1N11BX KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Enzyme Activation KW - Models, Molecular KW - Databases as Topic KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Transfection KW - Kinetics KW - Binding, Competitive KW - CHO Cells KW - Zinc Fingers KW - Molecular Conformation KW - Hydrogen Bonding KW - Phorbol 12,13-Dibutyrate -- pharmacokinetics KW - Protein Conformation KW - Cricetinae KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Diglycerides -- pharmacology KW - Diglycerides -- chemical synthesis KW - Protein Kinase C -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70884365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=An+optimized+protein+kinase+C+activating+diacylglycerol+combining+high+binding+affinity+%28Ki%29+with+reduced+lipophilicity+%28log+P%29.&rft.au=Nacro%2C+K%3BSigano%2C+D+M%3BYan%2C+S%3BNicklaus%2C+M+C%3BPearce%2C+L+L%3BLewin%2C+N+E%3BGarfield%2C+S+H%3BBlumberg%2C+P+M%3BMarquez%2C+V+E&rft.aulast=Nacro&rft.aufirst=K&rft.date=2001-06-07&rft.volume=44&rft.issue=12&rft.spage=1892&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2). AN - 70923699; 11406094 AB - The fluorescent compounds rhodamine 123, LysoTracker Green DMD-26, mitoxantrone, and BODIPY-prazosin were used with the antagonist fumitremorgin C (FTC) in order to develop functional assays for the half-transporter, MXR/BCRP/ABCP1. A measure of FTC-inhibitable efflux was generated for each compound in a series of MXR-overexpressing drug-selected cell lines and in ten unselected cell lines which were used to determine if the four fluorescent compounds were sensitive enough to detect the low MXR levels found in drug-sensitive cell lines. FTC-inhibitable efflux of mitoxantrone and prazosin was found in four of the ten cell lines, SF295, KM12, NCI-H460, and A549, and low but detectable levels of MXR mRNA were also observed by Northern analysis in these cells. FTC-inhibitable mitoxantrone and prazosin efflux in both selected and unselected cell lines was found to correlate well with MXR levels as determined by Northern blotting, r(2)=0.89 and r(2)=0.70 respectively. In contrast, rhodamine and LysoTracker were not able to reliably detect MXR. Cytotoxicity assays performed on two of the four unselected cell lines confirmed increased sensitivity to mitoxantrone in the presence of FTC. FTC was found to be a specific inhibitor of MXR, with half-maximal inhibition of MXR-associated ATPase activity at 1 microM FTC. Short term selections of the SF295, KM12, NCI-H460 and A549 cell lines in mitoxantrone resulted in a small but measurable increase in MXR by both Northern blot and functional assay. These studies show that flow cytometric measurement of FTC-inhibitable mitoxantrone or prazosin efflux is a sensitive and specific method for measuring the function of the MXR half-transporter in both selected and unselected cell lines. JF - Biochimica et biophysica acta AU - Robey, R W AU - Honjo, Y AU - van de Laar, A AU - Miyake, K AU - Regis, J T AU - Litman, T AU - Bates, S E AD - Developmental Therapeutics Department, Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2001/06/06/ PY - 2001 DA - 2001 Jun 06 SP - 171 EP - 182 VL - 1512 IS - 2 SN - 0006-3002, 0006-3002 KW - 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene KW - 0 KW - ABCG2 protein, human KW - ATP Binding Cassette Transporter, Sub-Family G, Member 2 KW - Boron Compounds KW - Fluorescent Dyes KW - Neoplasm Proteins KW - P-Glycoprotein KW - RNA, Messenger KW - Mitoxantrone KW - BZ114NVM5P KW - Verapamil KW - CJ0O37KU29 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Prazosin KW - XM03YJ541D KW - Index Medicus KW - Humans KW - Breast Neoplasms KW - Verapamil -- pharmacology KW - RNA, Messenger -- genetics KW - Gene Expression Regulation, Neoplastic KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - Kinetics KW - Prazosin -- pharmacokinetics KW - Colonic Neoplasms KW - Female KW - Mitoxantrone -- toxicity KW - Drug Resistance, Multiple -- physiology KW - Microsomes -- metabolism KW - ATP-Binding Cassette Transporters -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - Transcription, Genetic KW - Intracellular Membranes -- metabolism KW - Adenosine Triphosphatases -- genetics KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70923699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=A+functional+assay+for+detection+of+the+mitoxantrone+resistance+protein%2C+MXR+%28ABCG2%29.&rft.au=Robey%2C+R+W%3BHonjo%2C+Y%3Bvan+de+Laar%2C+A%3BMiyake%2C+K%3BRegis%2C+J+T%3BLitman%2C+T%3BBates%2C+S+E&rft.aulast=Robey&rft.aufirst=R&rft.date=2001-06-06&rft.volume=1512&rft.issue=2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High efficiency mutagenesis, repair, and engineering of chromosomal DNA using single-stranded oligonucleotides AN - 17891977; 5130912 AB - Homologous DNA recombination is a fundamental, regenerative process within living organisms. However, in most organisms, homologous recombination is a rare event, requiring a complex set of reactions and extensive homology. We demonstrate in this paper that Beta protein of phage lambda generates recombinants in chromosomal DNA by using synthetic single-stranded DNAs (ssDNA) as short as 30 bases long. This ssDNA recombination can be used to mutagenize or repair the chromosome with efficiencies that generate up to 6% recombinants among treated cells. Mechanistically, it appears that Beta protein, a Rad52-like protein, binds and anneals the ssDNA donor to a complementary single-strand near the DNA replication fork to generate the recombinant. This type of homologous recombination with ssDNA provides new avenues for studying and modifying genomes ranging from bacterial pathogens to eukaryotes. Beta protein and ssDNA may prove generally applicable for repairing DNA in many organisms. JF - Proceedings of the National Academy of Sciences, USA AU - Ellis, H M AU - Yu, D AU - DiTizio, T AU - Court, D L AD - Gene Regulation and Chromosome Biology Laboratory, Division of Basic Sciences, National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702, court@ncifcrf.gov Y1 - 2001/06/05/ PY - 2001 DA - 2001 Jun 05 SP - 6742 EP - 6746 VL - 98 IS - 12 SN - 0027-8424, 0027-8424 KW - Beta protein KW - Phage lambda KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Phage l KW - Recombination KW - Chromosomes KW - Phage ^l KW - DNA repair KW - Oligonucleotides KW - Mutagenesis KW - W3 33243:Molecular methods KW - N 14652:DNA repair KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17891977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=High+efficiency+mutagenesis%2C+repair%2C+and+engineering+of+chromosomal+DNA+using+single-stranded+oligonucleotides&rft.au=Ellis%2C+H+M%3BYu%2C+D%3BDiTizio%2C+T%3BCourt%2C+D+L&rft.aulast=Ellis&rft.aufirst=H&rft.date=2001-06-05&rft.volume=98&rft.issue=12&rft.spage=6742&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.121164898 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage ^l; DNA repair; Mutagenesis; Chromosomes; Recombination; Oligonucleotides DO - http://dx.doi.org/10.1073/pnas.121164898 ER - TY - JOUR T1 - Understanding the role of xenobiotic-metabolism in chemical carcinogenesis using gene knockout mice. AN - 70882128; 11376689 AB - Most chemical carcinogens require metabolic activation to electrophilic metabolites that are capable of binding to DNA and causing gene mutations. Carcinogen metabolism is carried out by large groups of xenobiotic-metabolizing enzymes that include the phase I cytochromes P450 (P450) and microsomal epoxide hydrolase, and various phase II transferase enzymes. It is extremely important to determine the role P450s play in the carcinogenesis and to establish if they are the rate limiting and critical interface between the chemical and its biological activities. The latter is essential in order to validate the use of rodent models to test safety of chemicals in humans. Since there are marked species differences in expressions and catalytic activities of the multiple P450 forms that activate carcinogens, this validation process becomes especially difficult. To address the role of P450s in whole animal carcinogenesis, mice were produced that lack the P450s known to catalyze carcinogen activation. Mouse lines having disrupted genes encoding the P450s CYP1A2, CYP2E1, and CYP1B1 were developed. Mice lacking expression of microsomal epoxide hydrolase (mEH) and NADPH-quinone oxidoreductase (NQO1) were also made. All of these mice exhibit no gross abnormal phenotypes, suggesting that the xenobiotic-metabolizing enzymes have no critical roles in mammalian development and physiological homeostasis. This explains the occurrence of polymorphisms in xenobiotic-metabolizing enzymes among humans and other mammalian species. However, these null mice do show differences in sensitivities to acute chemical toxicities, thus establishing the importance of xenobiotic metabolism in activation pathways that lead to cell death. Rodent bioassays using null mice and known genotoxic carcinogens should establish whether these enzymes are required for carcinogenesis in an intact animal model. These studies will also provide a framework for the production of transgenic mice and carcinogen bioassay protocols that may be more predictive for identifying the human carcinogens and validate the molecular epidemiological studies ongoing in humans that seek to establish a role for polymorphisms in cancer risk. JF - Mutation research AU - Gonzalez, F J AU - Kimura, S AD - National Institutes of Health, National Cancer Institute, Building 37 Room 3E-24, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2001/06/02/ PY - 2001 DA - 2001 Jun 02 SP - 79 EP - 87 VL - 477 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Benz(a)Anthracenes KW - 0 KW - Carcinogens KW - Xenobiotics KW - 7,12-dihydroxymethylbenz(a)anthracene KW - 2564-65-0 KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cyp1b1 protein, mouse KW - Cytochrome P-450 CYP1B1 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Benzene KW - J64922108F KW - Index Medicus KW - Epoxide Hydrolases -- metabolism KW - Animals KW - Humans KW - Benzene -- toxicity KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Benz(a)Anthracenes -- toxicity KW - Acetaminophen -- toxicity KW - Mice, Knockout KW - Neoplasms -- enzymology KW - Carcinogens -- metabolism KW - Xenobiotics -- metabolism KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Xenobiotics -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70882128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Understanding+the+role+of+xenobiotic-metabolism+in+chemical+carcinogenesis+using+gene+knockout+mice.&rft.au=Gonzalez%2C+F+J%3BKimura%2C+S&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=2001-06-02&rft.volume=477&rft.issue=1-2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaccines to die for AN - 864949507; 13695304 JF - Nature Biotechnology AU - Restifo, Nicholas P AD - Nicholas P. Restifo is a principal investigator at the National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (restifo[AT]nih.gov). Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 527 EP - 528 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 19 IS - 6 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864949507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Vaccines+to+die+for&rft.au=Restifo%2C+Nicholas+P&rft.aulast=Restifo&rft.aufirst=Nicholas&rft.date=2001-06-01&rft.volume=19&rft.issue=6&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F89255 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2012-03-29 DO - http://dx.doi.org/10.1038/89255 ER - TY - JOUR T1 - Associating Semantic Space Abnormalities with Formal Thought Disorder in Schizophrenia: Use of Triadic Comparisons AN - 85542587; 200113353 AB - Recent studies of schizophrenia have suggested that thought disorder results from abnormalities in semantic processing. In the following pilot study, the cognitive system used for organizing & associating concepts was examined using a triadic comparison task. The semantic maps of schizophrenia patients with high thought disorder (N = 5) were compared to that of schizophrenia patients with low levels of thought disorder (N = 5) & normal controls (N = 10) with multidimensional scaling analysis. At initial testing & at retest, patients with high levels of thought disorder exhibited consistently lower semantic goodness of fit scores & failed to map results of triadic comparisons along well-defined dimensions. Results suggest that thought disorder in schizophrenia is related to a disturbance in the organization of semantic networks. 4 Tables, 3 Figures, 31 References. Adapted from the source document JF - Journal of Clinical and Experimental Neuropsychology AU - Tallent, Kathleen A AU - Weinberger, Daniel R AU - Goldberg, Terry E AD - c/o Goldberg-Clincal Brain Disorders Branch, National Instit Mental Health, Bethesda, MD goldbert@intra.nimh.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 285 EP - 296 VL - 23 IS - 3 SN - 1380-3395, 1380-3395 KW - Schizophrenia (75250) KW - Psychometric Analysis (69210) KW - Semantic Processing (76760) KW - article KW - 6710: linguistics and psychiatry; linguistics and psychiatry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85542587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+and+Experimental+Neuropsychology&rft.atitle=Associating+Semantic+Space+Abnormalities+with+Formal+Thought+Disorder+in+Schizophrenia%3A+Use+of+Triadic+Comparisons&rft.au=Tallent%2C+Kathleen+A%3BWeinberger%2C+Daniel+R%3BGoldberg%2C+Terry+E&rft.aulast=Tallent&rft.aufirst=Kathleen&rft.date=2001-06-01&rft.volume=23&rft.issue=3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+and+Experimental+Neuropsychology&rft.issn=13803395&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - JCENE8 N1 - SubjectsTermNotLitGenreText - Schizophrenia (75250); Semantic Processing (76760); Psychometric Analysis (69210) ER - TY - JOUR T1 - Brain Plasticity and Recovery from Hemiplegia AN - 85347352; llba-200108789 AB - The brain is capable of considerable reorganization even in adult life. This has been extensively studied in the motor system & can be demonstrated in a number of situations including deafferentation of a body part (eg, in an amputation) & motor learning. Techniques including neuroimaging & transcranial magnetic stimulation (TMS) can be used to demonstrate this plasticity by mapping representations in the brain; TMS can also be useful in assessing excitability & briefly deactivating brain regions. With brain lesions such as stroke, there can be considerable spontaneous recovery, & this appears to be due to plastic changes. Some recovery may be mediated by enhanced activity in ipsilateral pathways; this is most clear in the recovery of swallowing. The best recovery of the upper extremity after stroke, however, is due to reorganization of the lesioned hemisphere. Rehabilitative strategies might well be able to enhance rehabilitative efforts. 2 Figures, 61 References. Adapted from the source document JF - Journal of Medical Speech-Language Pathology AU - Hallett, Mark AD - Human Motor Control Section, NINDS, NIH, Bethesda, MD hallettm@ninds.nih.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 107 EP - 115 VL - 9 IS - 2 SN - 1065-1438, 1065-1438 KW - *Nervous System Disorders (57100) KW - *Therapy (89500) KW - *Brain Damage (09400) KW - *Brain (09350) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85347352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Medical+Speech-Language+Pathology&rft.atitle=Brain+Plasticity+and+Recovery+from+Hemiplegia&rft.au=Hallett%2C+Mark&rft.aulast=Hallett&rft.aufirst=Mark&rft.date=2001-06-01&rft.volume=9&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Speech-Language+Pathology&rft.issn=10651438&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2003-10-01 N1 - Last updated - 2014-06-17 N1 - CODEN - JSLPEP N1 - SubjectsTermNotLitGenreText - *Brain (09350); *Nervous System Disorders (57100); *Therapy (89500); *Brain Damage (09400) ER - TY - JOUR T1 - Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. AN - 85271133; pmid-11409421 AB - Aminoglycosides have previously been shown to suppress nonsense mutations, allowing translation of full-length proteins in vitro and in animal models. In the mdx mouse, where muscular dystrophy is due to a nonsense mutation in the dystrophin gene, gentamicin suppressed truncation of the protein and ameliorated the phenotype. A subset of patients with Duchenne and Becker muscular dystrophy similarly possess a nonsense mutation, causing premature termination of dystrophin translation. Four such patients, with various stop codon sequences, were treated once daily with intravenous gentamicin at 7.5 mg/kg/day for 2 weeks. No ototoxicity or nephrotoxicity was detected. Full-length dystrophin was not detected in pre- and post-treatment muscle biopsies. JF - Annals of Neurology AU - Wagner, K R AU - Hamed, S AU - Hadley, D W AU - Gropman, A L AU - Burstein, A H AU - Escolar, D M AU - Hoffman, E P AU - Fischbeck, K H AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. PY - 2001 SP - 706 EP - 711 VL - 49 IS - 6 SN - 0364-5134, 0364-5134 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Dystrophin KW - Biopsy KW - Child KW - Muscle, Skeletal KW - Codon, Nonsense KW - Phenotype KW - Blotting, Western KW - Creatine Kinase KW - Muscular Dystrophy, Duchenne KW - Gentamicins KW - Treatment Outcome KW - Support, Non-U.S. Gov't KW - Adolescent UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85271133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Neurology&rft.atitle=Gentamicin+treatment+of+Duchenne+and+Becker+muscular+dystrophy+due+to+nonsense+mutations.&rft.au=Wagner%2C+K+R%3BHamed%2C+S%3BHadley%2C+D+W%3BGropman%2C+A+L%3BBurstein%2C+A+H%3BEscolar%2C+D+M%3BHoffman%2C+E+P%3BFischbeck%2C+K+H&rft.aulast=Wagner&rft.aufirst=K&rft.date=2001-06-01&rft.volume=49&rft.issue=6&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Annals+of+Neurology&rft.issn=03645134&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Nested case-control analysis of high pesticide exposure events from the Agricultural Health Study. AN - 85258964; pmid-11385639 AB - BACKGROUND: A nested case-control analysis of high pesticide exposure events (HPEEs) was conducted using the Iowa farmers enrolled in the Agricultural Health Study (AHS). METHODS: In the 12 months of the study, 36 of the 5,970 farmer applicators randomly chosen from the AHS cohort (six per 1,000 farmer applicators per year) met our definition of an HPEE, by reporting "an incident with fertilizers, weed killers, or other pesticides that caused an unusually high personal exposure" resulting in physical symptoms or a visit to a health care provider or hospital. Eligibility criteria were met by 25 HPEE cases and 603 randomly selected controls. RESULTS: Significant risk factors for an HPEE included: poor financial condition of the farm which limited the purchase of rollover protective structures OR = 4.6 (1.5-16.6), and having a high score on a risk acceptance scale OR = 3.8 (1.4-11.2). Other non-significant factors were also identified. CONCLUSIONS: The limited statistical power of this study necessitates replication of these analyses with a larger sample. Nonetheless, the observed elevated odds ratios of an HPEE provide hypotheses for future studies that may lead to preventive action. JF - American Journal of Industrial Medicine AU - Alavanja, M C AU - Sprince, N L AU - Oliver, E AU - Whitten, P AU - Lynch, C F AU - Gillette, P P AU - Logsden-Sacket, N AU - Zwerling, C AD - Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd.(EPS), Rm. 8000, Rockville, MD, USA. PY - 2001 SP - 557 EP - 563 VL - 39 IS - 6 SN - 0271-3586, 0271-3586 KW - Occupational Exposure KW - Odds Ratio KW - Analysis of Variance KW - Questionnaires KW - Logistic Models KW - Human KW - Pesticides KW - Health Surveys KW - Adult KW - Case-Control Studies KW - Middle Age KW - Male KW - Agriculture KW - Risk-Taking KW - Accidents, Occupational UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85258964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Nested+case-control+analysis+of+high+pesticide+exposure+events+from+the+Agricultural+Health+Study.&rft.au=Alavanja%2C+M+C%3BSprince%2C+N+L%3BOliver%2C+E%3BWhitten%2C+P%3BLynch%2C+C+F%3BGillette%2C+P+P%3BLogsden-Sacket%2C+N%3BZwerling%2C+C&rft.aulast=Alavanja&rft.aufirst=M&rft.date=2001-06-01&rft.volume=39&rft.issue=6&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Evidence of a Hopf bifurcation in frog hair cells. AN - 85257927; pmid-11371437 AB - The membrane potential of hair cells in the low-frequency hearing organ of the bullfrog, the amphibian papilla, sinusoidally oscillates at small amplitude in the absence of acoustical input. We stimulate the cell with a series of periodic currents close to this natural frequency and observe that its current-to-voltage transfer function is compressively nonlinear, having a large gain for small stimuli and a smaller gain for larger currents. Along with the spontaneous oscillation, this implies that the cell is poised close to a dynamical instability such as a Hopf bifurcation, because distant from the instability the transfer function becomes linear. The cell's frequency selectivity is enhanced for small stimuli. Simulations show that the cell's membrane capacitance is effectively reduced due to a current gain provided by this dynamical instability. We propose that the Hopf resonance is widely used by transducer cells on the sensory periphery to achieve small-signal amplification. JF - Biophysical Journal AU - Ospeck, M AU - Eguíluz V M AU - Magnasco, M O AD - Biophysics Section, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-0922, USA. PY - 2001 SP - 2597 EP - 2607 VL - 80 IS - 6 SN - 0006-3495, 0006-3495 KW - Support, U.S. Gov't, P.H.S. KW - Microscopy, Phase-Contrast KW - Hair Cells KW - Electric Conductivity KW - Rana catesbeiana KW - Endolymph KW - Animal KW - Support, Non-U.S. Gov't KW - Membrane Potentials KW - Potassium KW - Acoustic Stimulation KW - Models, Biological KW - Potassium Channels UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85257927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Evidence+of+a+Hopf+bifurcation+in+frog+hair+cells.&rft.au=Ospeck%2C+M%3BEgu%C3%ADluz+V+M%3BMagnasco%2C+M+O&rft.aulast=Ospeck&rft.aufirst=M&rft.date=2001-06-01&rft.volume=80&rft.issue=6&rft.spage=2597&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Differential zinc and DNA binding by partial peptides of human protamine HP2 AN - 815537018; 13861522 AB - The Zn(II) binding by partial peptides of human protamine HP2: HP2 sub(1-15); HP2 sub(1-25), HP2 sub(26-40), HP2 sub(37-47), and HP2 sub(43-57) was studied by circular dichroism (CD). Precipitation of a 20-mer DNA by these partial peptides and the effects of Zn(II) thereon were investigated using polyacrylamide gel electrophoresis (GE). The results of this study suggest that reduced HP2 (thiol groups intact) can bind Zn(II) at various parts of the molecule. In the absence of DNA, the primary Zn(II) binding site in reduced HP2 is located in the 37-47 sequence (involving Cys-37, His-39, His-43, and Cys-47), while in the presence of DNA, the strongest Zn(II) binding is provided by sequences 12-22 (by His-12, Cys-13, His-19, and His-22) and 43-57 (His-43, Cys-47, Cys-53, and His-57). In its oxidized form, HP2 can bind zinc through His residues of the 7-22 sequence. Zn(II) markedly enhances DNA binding by all partial peptides. These findings suggest that Zn(II) ions may be a regulatory factor for sperm chromatin condensation processes. JF - Molecular and Cellular Biochemistry AU - Bal, Wojciech AU - Dyba, Marcin AU - Szewczuk, Zbigniew AU - Jeowska-Bojczuk, Magorzata AU - Lukszo, Jan AU - Ramakrishna, Gayatri AU - Kasprzak, Kazimierz S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD, 21702-1201, USA, wbal@wchuwr.chem.uni.wroc.pl Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 97 EP - 106 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 222 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - Ions KW - Chromatin KW - Nucleotide sequence KW - Precipitation KW - Sperm KW - Gel electrophoresis KW - protamine KW - C.D. KW - Zinc KW - Thiols KW - DNA KW - Condensation KW - X 24360:Metals KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815537018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Cellular+Biochemistry&rft.atitle=Differential+zinc+and+DNA+binding+by+partial+peptides+of+human+protamine+HP2&rft.au=Bal%2C+Wojciech%3BDyba%2C+Marcin%3BSzewczuk%2C+Zbigniew%3BJeowska-Bojczuk%2C+Magorzata%3BLukszo%2C+Jan%3BRamakrishna%2C+Gayatri%3BKasprzak%2C+Kazimierz+S&rft.aulast=Bal&rft.aufirst=Wojciech&rft.date=2001-06-01&rft.volume=222&rft.issue=1-2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biochemistry&rft.issn=03008177&rft_id=info:doi/10.1023%2FA%3A1017971525105 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Ions; Chromatin; protamine; C.D.; Nucleotide sequence; Thiols; Zinc; DNA; Condensation; Sperm; Precipitation; Gel electrophoresis DO - http://dx.doi.org/10.1023/A:1017971525105 ER - TY - JOUR T1 - Novel approaches in the treatment of lupus nephritis. AN - 72387631; 11772239 AB - In systemic lupus erythematosus hyperactive helper T-cells drive polyclonal B-cell activation and secretion of pathogenic auto-antibodies. The auto-antibodies form immune complexes with their respective auto-antigens, which in turn deposit in sites such as the kidney and initiate a destructive inflammatory reaction. Lupus nephritis can be managed successfully in the majority of cases; however, the most widely used immunosuppressive therapies, notably corticosteroids and cyclophosphamide are non-specific and are associated with substantial toxicities. Novel treatments for lupus nephritis have to be at least as effective and less toxic than existing therapies. The ultimate aim is to develop treatments that target specific steps in the disease process. Novel therapeutic strategies in the short-term more likely will focus on refining regimens of drugs that are already in use (mycophenolate mofetil, adenosine analogues) and combinations of existing chemotherapeutic agents, as well as attempts to achieve immunological reconstitution using immunoablative chemotherapy with or without haematopoietic stem cell rescue. Several new agents targeting specific steps in the pathogenesis of lupus are in various phases of clinical development. Interrupting the interactions between T-lymphocytes and other cells by blocking co-stimulatory molecules, such as CD40 ligand or CTLA4-Ig, may interfere with the early steps of pathogenesis. Blocking IL-10 may decrease auto-antibody production and help normalise T-cell function. Treating patients with DNase or interfering with the complement cascade by blocking C5, or neutralising pathogenic antibodies by administering specific binding peptides or inducing specific anti-idiotype antibodies may prevent immune complex formation and/or deposition. JF - Expert opinion on investigational drugs AU - Illei, G G AU - Czirják, L AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Rm 9S205, Bethesda, MD 20892, USA. illeig@mail.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1117 EP - 1130 VL - 10 IS - 6 SN - 1354-3784, 1354-3784 KW - Immunologic Factors KW - 0 KW - Immunosuppressive Agents KW - Index Medicus KW - Animals KW - Immunologic Factors -- therapeutic use KW - Humans KW - Drug Delivery Systems -- methods KW - Immunosuppressive Agents -- therapeutic use KW - Lupus Nephritis -- drug therapy KW - Lupus Nephritis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72387631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Novel+approaches+in+the+treatment+of+lupus+nephritis.&rft.au=Illei%2C+G+G%3BCzirj%C3%A1k%2C+L&rft.aulast=Illei&rft.aufirst=G&rft.date=2001-06-01&rft.volume=10&rft.issue=6&rft.spage=1117&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=13543784&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-14 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abnormal ACTH-stimulation test in a patient with AIDS: adrenal insufficiency or toxoplasmosis? AN - 71181101; 11563937 AB - We here report a 32-year old homosexual man with AIDS who had an abnormal ACTH stimulation test while taking megestrol actetate (megace). On further evaluation, he was found to have recurrent Non-Hodgkin lymphoma (spleen) and intracranial toxoplasmosis, perhaps imitating or aggravating symptoms suggestive of adrenal insufficiency (AI). We diagnosed secondary AI due to megace treatment and tapered this medication under simultaneous hydrocortisone replacement therapy. After the patient's intracranial toxoplasmosis had been treated with intravenous bactrim, his symptoms disappeared. We conclude that patients with AIDS on megace therapy should receive special attention in regards to the potential development of AI, especially in stress situations such as infections or pain. JF - Endocrine regulations AU - Koch, C A AU - Pacak, K AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Helath and Human Development, National Intitutes of Health, Bethesda, MD 20892, USA. kochc@exchange.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 91 EP - 93 VL - 35 IS - 2 SN - 1210-0668, 1210-0668 KW - Anti-Infective Agents KW - 0 KW - Trimethoprim, Sulfamethoxazole Drug Combination KW - 8064-90-2 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Megestrol Acetate KW - TJ2M0FR8ES KW - Index Medicus KW - Anti-Infective Agents -- therapeutic use KW - Diagnosis, Differential KW - Humans KW - Trimethoprim, Sulfamethoxazole Drug Combination -- therapeutic use KW - Adult KW - Megestrol Acetate -- antagonists & inhibitors KW - Male KW - Adrenal Insufficiency -- diagnosis KW - Toxoplasmosis, Cerebral -- drug therapy KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Adrenal Insufficiency -- chemically induced KW - Toxoplasmosis, Cerebral -- diagnosis KW - Acquired Immunodeficiency Syndrome -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71181101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine+regulations&rft.atitle=Abnormal+ACTH-stimulation+test+in+a+patient+with+AIDS%3A+adrenal+insufficiency+or+toxoplasmosis%3F&rft.au=Koch%2C+C+A%3BPacak%2C+K&rft.aulast=Koch&rft.aufirst=C&rft.date=2001-06-01&rft.volume=35&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Endocrine+regulations&rft.issn=12100668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol. AN - 71069701; 11484844 AB - 2-butoxyethanol (BE; ethylene glycol monobutyl ether) is used extensively in the manufacture of a wide range of domestic and industrial products which may result in human exposure and toxicity. BE causes severe hemolytic anemia in male and female rats and mice. In a recent report, female F344 rats exposed to 500 ppm BE by inhalation and sacrificed moribund on day 4 of treatment exhibited disseminated thrombosis associated with infarction in several organs. In contrast, no such lesions were observed in male rats similarly exposed to BE. Additional studies were therefore undertaken to compare the effects of BE in rats of both sexes. Rats received 250 mg BE/kg/day by gavage for 1, 2 or 3 days and were sacrificed 24 or 48 hr after the last dose. Control rats received 5 ml/kg water. Progressive time-dependent hemolytic anemia--macrocytic, hypochromic, and regenerative--was observed in both sexes of rats exposed to BE. Additionally, BE caused significant morphological changes in erythrocytes, first observed 24 hr after a single dose, including stomatocytosis, macrocytosis with moderate rouleaux formation, and spherocytosis. These morphological changes became progressively more severe as BE dosing continued and included the occasional occurrence of schistocytes and ghost cells, rouleaux formation in rats of both sexes, and an increased number of red blood cells with micronuclei in female rats. Overall, the progression of hemolytic anemia and morphological changes as a function of the number of days of exposure varied with gender and suggested a faster onset of hemolysis in female rats. The range of BE-related histopathological changes noted in both sexes was comparable; however, while these lesions were observed in female rats following a single dose, similar effects were first observed in males after 3 consecutive days of exposure to BE. Pathological changes involved disseminated thrombosis in the lungs, nasal submucosa, eyes, liver, heart, bones and teeth, with evidence of infarction in the heart, eyes, teeth and bones. Hemoglobinuric nephrosis and splenic extramedullary hematopoiesis were also noted. An apparent correlation between the severity of hemolytic anemia and subsequent disseminated thrombosis in BE-treated rats is proposed. Thrombosis may be related to intravascular hemolysis, which could be triggered by procoagulant release and/or alterations in erythrocyte morphology, as well as increased rigidity. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Ghanayem, B I AU - Long, P H AU - Ward, S M AU - Chanas, B AU - Nyska, M AU - Nyska, A AD - National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Ghanayem@niehs.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 97 EP - 105 VL - 53 IS - 2-3 SN - 0940-2993, 0940-2993 KW - Ethylene Glycols KW - 0 KW - Solvents KW - n-butoxyethanol KW - I0P9XEZ9WV KW - Index Medicus KW - Administration, Oral KW - Animals KW - Erythrocytes -- drug effects KW - Anemia, Hypochromic -- chemically induced KW - Anemia, Macrocytic -- chemically induced KW - Sex Factors KW - Tooth -- drug effects KW - Anemia, Hypochromic -- pathology KW - Femur -- pathology KW - Rats KW - Hemolysis -- drug effects KW - Odontoblasts -- drug effects KW - Tooth -- pathology KW - Rats, Inbred F344 KW - Anemia, Macrocytic -- pathology KW - Odontoblasts -- pathology KW - Male KW - Erythrocytes -- pathology KW - Female KW - Femur -- drug effects KW - Thrombosis -- chemically induced KW - Anemia, Hemolytic -- pathology KW - Solvents -- toxicity KW - Anemia, Hemolytic -- chemically induced KW - Thrombosis -- pathology KW - Ethylene Glycols -- toxicity KW - Infarction -- chemically induced KW - Solvents -- administration & dosage KW - Ethylene Glycols -- administration & dosage KW - Infarction -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71069701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=Hemolytic+anemia%2C+thrombosis%2C+and+infarction+in+male+and+female+F344+rats+following+gavage+exposure+to+2-butoxyethanol.&rft.au=Ghanayem%2C+B+I%3BLong%2C+P+H%3BWard%2C+S+M%3BChanas%2C+B%3BNyska%2C+M%3BNyska%2C+A&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=2001-06-01&rft.volume=53&rft.issue=2-3&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=09402993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-13 N1 - Date created - 2001-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study on the relation between cisplatin neuropathy and vitamin E. AN - 71054939; 11484987 AB - Peripheral sensory neuropathy is the main non-hematological side-effect related to cisplatin chemotherapy. The strong similarity between clinical and neuropathological aspects in peripheral neuropathy induced by cisplatin and neurologic syndromes due to vitamin E deficiency, prompted us to investigate the relationship between cisplatin neuropathy and plasmatic level of vitamin E (alpha-tocopherol). We measured vitamin E in the plasma of 5 patients (Group 1) which developed severe neurotoxicity after cisplatin treatment and in another group of 5 patients (Group 2) we analyzed the plasmatic level of vitamin E before and after 2 or 4 cycles of cisplatin treatment. The results showed that the patients of group 1 presented low plasmatic levels of vitamin E and that the patients of group 2 presented significantly lower levels of vitamin E after 2 or 4 cycles of cisplatin than before treatment. Our preliminary data suggest that an inadequate amount of the antioxidant vitamin E due to cisplatin treatment could be responsible of the peripheral nerve damage induced by free-radicals. Given the lack of toxicity of vitamin E, we need to systematically assess the possible neuroprotective role of vitamin E supplementation in patients treated with cisplatin chemotherapy. JF - Journal of experimental & clinical cancer research : CR AU - Bove, L AU - Picardo, M AU - Maresca, V AU - Jandolo, B AU - Pace, A AD - Service of Neurology, Regina Elena National Cancer Institute, Rome, Italy. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 277 EP - 280 VL - 20 IS - 2 SN - 0392-9078, 0392-9078 KW - Antineoplastic Agents KW - 0 KW - Antioxidants KW - Neuroprotective Agents KW - Vitamin E KW - 1406-18-4 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Neoplasms -- drug therapy KW - Drug Administration Schedule KW - Humans KW - Adult KW - Aged KW - Pilot Projects KW - Middle Aged KW - Antioxidants -- metabolism KW - Peripheral Nervous System Diseases -- blood KW - Cisplatin -- adverse effects KW - Peripheral Nervous System Diseases -- chemically induced KW - Vitamin E -- blood KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71054939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=A+pilot+study+on+the+relation+between+cisplatin+neuropathy+and+vitamin+E.&rft.au=Bove%2C+L%3BPicardo%2C+M%3BMaresca%2C+V%3BJandolo%2C+B%3BPace%2C+A&rft.aulast=Bove&rft.aufirst=L&rft.date=2001-06-01&rft.volume=20&rft.issue=2&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-18 N1 - Date created - 2001-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of the behavioral and neurochemical effects of psychostimulants by kappa-opioid receptor systems. AN - 71034757; 11458540 AB - The repeated, intermittent use of cocaine and other drugs of abuse produces profound and often long-lasting alterations in behavior and brain chemistry. It has been suggested that these consequences of drug use play a critical role in drug craving and relapse to addiction. This article reviews the effects of psychostimulant administration on dopaminergic and excitatory amino acid neurotransmission in brain regions comprising the brain's motive circuit and provides evidence that the activation of endogenous kappa-opioid receptor systems in these regions opposes the behavioral and neurochemical consequences of repeated drug use. The role of this opioid system in mediating alterations in mood and affect that occur during abstinence from repeated psychostimulant use are also discussed. JF - Annals of the New York Academy of Sciences AU - Shippenberg, T S AU - Chefer, V I AU - Zapata, A AU - Heidbreder, C A AD - Integrative Neuroscience Unit, NIDA Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. tshippen@intra.nida.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 50 EP - 73 VL - 937 SN - 0077-8923, 0077-8923 KW - Dopamine Uptake Inhibitors KW - 0 KW - Ligands KW - Receptors, Dopamine KW - Receptors, Opioid, kappa KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Animals KW - Receptors, Dopamine -- physiology KW - Thalamic Nuclei -- physiology KW - Adaptation, Psychological KW - Humans KW - Brain Chemistry -- drug effects KW - Thalamic Nuclei -- drug effects KW - Basal Ganglia -- physiology KW - Affect KW - Basal Ganglia -- drug effects KW - Cocaine-Related Disorders -- physiopathology KW - Receptors, Opioid, kappa -- drug effects KW - Receptors, Opioid, kappa -- physiology KW - Cocaine -- pharmacology KW - Amphetamine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71034757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Modulation+of+the+behavioral+and+neurochemical+effects+of+psychostimulants+by+kappa-opioid+receptor+systems.&rft.au=Shippenberg%2C+T+S%3BChefer%2C+V+I%3BZapata%2C+A%3BHeidbreder%2C+C+A&rft.aulast=Shippenberg&rft.aufirst=T&rft.date=2001-06-01&rft.volume=937&rft.issue=&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose chemotherapy for rhabdomyosarcoma: where do we go from here. AN - 71029456; 11464979 JF - Journal of pediatric hematology/oncology AU - Mackall, C L AU - Helman, L J AD - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. PY - 2001 SP - 266 EP - 267 VL - 23 IS - 5 SN - 1077-4114, 1077-4114 KW - Index Medicus KW - Multicenter Studies as Topic KW - Randomized Controlled Trials as Topic KW - Survival Rate KW - Bone Marrow Diseases -- chemically induced KW - Humans KW - Treatment Outcome KW - Hematopoietic Stem Cell Transplantation KW - Bone Marrow Diseases -- therapy KW - Pilot Projects KW - Forecasting KW - Child KW - Soft Tissue Neoplasms -- mortality KW - Soft Tissue Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Rhabdomyosarcoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Rhabdomyosarcoma -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71029456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pediatric+hematology%2Foncology&rft.atitle=High-dose+chemotherapy+for+rhabdomyosarcoma%3A+where+do+we+go+from+here.&rft.au=Mackall%2C+C+L%3BHelman%2C+L+J&rft.aulast=Mackall&rft.aufirst=C&rft.date=2001-06-01&rft.volume=23&rft.issue=5&rft.spage=266&rft.isbn=&rft.btitle=&rft.title=Journal+of+pediatric+hematology%2Foncology&rft.issn=10774114&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: J Pediatr Hematol Oncol. 2001 Jun-Jul;23(5):272-6 [11464981] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of systemic vasculitis. AN - 71028753; 11469822 AB - The systemic vasculitides are a wide-ranging group of diseases that are characterized by the presence of blood vessel inflammation. Despite this common feature, each type of vasculitis has a unique variety of clinical manifestations that influences its degree of disease severity and ultimately its management. Immunosuppressive therapy forms the foundation of treatment for almost all forms of systemic vasculitis. Because of this, treatment can be associated with its own risk of morbidity, or even mortality, related to specific medication side-effects or infections which occur as a result of impaired host defences. This chapter seeks to review the approach to management in selected forms of systemic vasculitis. Questions examined include the following. When should one treat systemic vasculitis? How does the nature of the disease and its severity affect treatment decisions? What are the data regarding the effectiveness of individual therapeutic regimens? Copyright 2001 Harcourt Publishers Ltd. JF - Best practice & research. Clinical rheumatology AU - Langford, C A AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 281 EP - 297 VL - 15 IS - 2 SN - 1521-6942, 1521-6942 KW - Drug Combinations KW - 0 KW - Glucocorticoids KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Azathioprine KW - MRK240IY2L KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- therapeutic use KW - Humans KW - Azathioprine -- therapeutic use KW - Methotrexate -- therapeutic use KW - Glucocorticoids -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Granulomatosis with Polyangiitis -- drug therapy KW - Vasculitis -- physiopathology KW - Vasculitis -- drug therapy KW - Vasculitis -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71028753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Best+practice+%26+research.+Clinical+rheumatology&rft.atitle=Management+of+systemic+vasculitis.&rft.au=Langford%2C+C+A&rft.aulast=Langford&rft.aufirst=C&rft.date=2001-06-01&rft.volume=15&rft.issue=2&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Best+practice+%26+research.+Clinical+rheumatology&rft.issn=15216942&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiviral medications improve cerebrovascular perfusion in HIV+ non-drug users and HIV+ cocaine abusers. AN - 71022030; 11462795 AB - Antiviral medications have been useful in delaying the time course of HIV infection. Antiviral medications have also been reported to delay or reduce symptoms associated with AIDS related dementia and to improve cortical perfusion. The mechanism for this improvement is unclear. Thus, this report studies the effects of antiviral medications on cerebral blood flow velocity in HIV+ cocaine abusers, HIV+ control individuals and appropriate control individuals. Thirty-two unmedicated HIV+ individuals (28 cocaine abusers and 4 control individuals), 22 HIV+ individuals using antiviral medications (16 cocaine abusers and 6 HIV+ control individuals), 47 HIV- cocaine abusers, and 27 control HIV- subjects were studied. Blood flow velocities were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography. HIV+ individuals on antiviral medications had lower pulsatility values, suggesting decreased resistance in the cerebral blood vessels, in comparison to HIV+ individuals not taking antiviral medications. HIV+ cocaine abusers and HIV+ control individuals using antiviral medications had pulsatility values similar to HIV- control subjects. Antiviral medications appear to reduce these cerebrovascular perfusion deficits in HIV+ individuals. The antiviral medications appear to have a direct neuroprotective effect in addition to their antiviral effects. The neuroprotective role of antiviral medications requires further investigation. JF - Annals of the New York Academy of Sciences AU - Herning, R I AU - Better, W E AU - Tate, K AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. rherning@intra.nida.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 405 EP - 412 VL - 939 SN - 0077-8923, 0077-8923 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - Middle Cerebral Artery -- physiology KW - Anterior Cerebral Artery -- drug effects KW - Anterior Cerebral Artery -- physiology KW - Pulsatile Flow -- drug effects KW - Humans KW - Blood Flow Velocity -- drug effects KW - AIDS Dementia Complex -- physiopathology KW - Pulsatile Flow -- physiology KW - AIDS Dementia Complex -- drug therapy KW - Middle Cerebral Artery -- drug effects KW - Blood Flow Velocity -- physiology KW - Adult KW - Middle Aged KW - Female KW - Male KW - HIV Infections -- physiopathology KW - Antiviral Agents -- therapeutic use KW - Cerebrovascular Circulation -- physiology KW - Cerebrovascular Circulation -- drug effects KW - Antiviral Agents -- pharmacology KW - HIV Infections -- drug therapy KW - Cocaine-Related Disorders -- drug therapy KW - Cocaine-Related Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71022030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Antiviral+medications+improve+cerebrovascular+perfusion+in+HIV%2B+non-drug+users+and+HIV%2B+cocaine+abusers.&rft.au=Herning%2C+R+I%3BBetter%2C+W+E%3BTate%2C+K%3BCadet%2C+J+L&rft.aulast=Herning&rft.aufirst=R&rft.date=2001-06-01&rft.volume=939&rft.issue=&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Marijuana abusers are at increased risk for stroke. Preliminary evidence from cerebrovascular perfusion data. AN - 71021868; 11462796 AB - We have recorded blood flow velocity in the anterior and middle cerebral arteries by transcranial Doppler sonography in abstinent marijuana abusers (n = 16) and control subjects (n = 19) to assess the effects of prolonged marijuana use of the cerebrovascular system. The pulsatility index, a measure of cerebrovascular resistance, and systolic velocity were significantly (p < 0.005) increased in marijuana abusers compared to the control subjects. These findings suggest that cerebral perfusion observed in 18-30 year old marijuana abusers is comparable to that of normal 60 year-olds. Thus, chronic abuse of marijuana might be a risk factor for stroke. JF - Annals of the New York Academy of Sciences AU - Herning, R I AU - Better, W E AU - Tate, K AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. rherning@intra.nida.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 413 EP - 415 VL - 939 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Blood Flow Velocity -- physiology KW - Risk Factors KW - Humans KW - Adult KW - Adolescent KW - Stroke -- chemically induced KW - Male KW - Middle Cerebral Artery -- physiology KW - Anterior Cerebral Artery -- physiology KW - Marijuana Abuse -- complications KW - Cerebrovascular Circulation -- physiology KW - Pulsatile Flow -- physiology KW - Marijuana Abuse -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71021868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Marijuana+abusers+are+at+increased+risk+for+stroke.+Preliminary+evidence+from+cerebrovascular+perfusion+data.&rft.au=Herning%2C+R+I%3BBetter%2C+W+E%3BTate%2C+K%3BCadet%2C+J+L&rft.aulast=Herning&rft.aufirst=R&rft.date=2001-06-01&rft.volume=939&rft.issue=&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Corticotropin-releasing hormone protects neurons against insults relevant to the pathogenesis of Alzheimer's disease. AN - 71021509; 11442356 AB - We previously reported that mice over-expressing the human amyloid precursor protein gene with the double Swedish mutation of familial Alzheimer's disease (mtAPP), which exhibit progressive deposition of amyloid beta-peptide in hippocampal and cortical brain regions, have an impaired ability to maintain a sustained glucocorticoid response to stress. Corticotropin releasing hormone (CRH), which initiates neuroendocrine responses to stress by activating the hypothalamic-pituitary-adrenal (HPA) axis, is expressed in brain regions prone to degeneration in Alzheimer's disease. We therefore tested the hypothesis that CRH can modify neuronal vulnerability to amyloid beta-peptide toxicity. In primary neuronal culture, CRH was protective against cell death caused by an amyloid-beta peptide, an effect that was blocked by a CRH receptor antagonist and by an inhibitor of cyclic AMP-dependent protein kinase. The increased resistance of CRH-treated neurons to amyloid toxicity was associated with stabilization of cellular calcium homeostasis. Moreover, CRH protected neurons against death caused by lipid peroxidation and the excitotoxic neurotransmitter glutamate. The level of mRNA encoding CRH was unchanged in mtAPP mouse brain, whereas the levels of mRNAs encoding glucocorticoid and mineralocorticoid receptors were subtly altered. Our results suggest that disturbances in HPA axis function can occur independently of alterations in CRH mRNA levels in Alzheimer's disease brain and further suggest an additional role for CRH in protecting neurons against cell death. Copyright 2001 Academic Press. JF - Neurobiology of disease AU - Pedersen, W A AU - McCullers, D AU - Culmsee, C AU - Haughey, N J AU - Herman, J P AU - Mattson, M P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 492 EP - 503 VL - 8 IS - 3 SN - 0969-9961, 0969-9961 KW - Amyloid beta-Peptides KW - 0 KW - Glucocorticoids KW - Neuroprotective Agents KW - RNA, Messenger KW - Glutamic Acid KW - 3KX376GY7L KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Cyclic AMP KW - E0399OZS9N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Cerebral Cortex -- cytology KW - Animals KW - Hypothalamo-Hypophyseal System -- drug effects KW - Mice, Transgenic KW - Homeostasis -- drug effects KW - Nerve Degeneration -- etiology KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Calcium -- metabolism KW - Nerve Degeneration -- drug therapy KW - Apoptosis -- drug effects KW - Amyloid beta-Peptides -- pharmacology KW - Nerve Degeneration -- pathology KW - Hypothalamo-Hypophyseal System -- pathology KW - Gene Expression -- physiology KW - Pituitary-Adrenal System -- drug effects KW - Glucocorticoids -- metabolism KW - Glutamic Acid -- metabolism KW - Pituitary-Adrenal System -- pathology KW - RNA, Messenger -- analysis KW - Lipid Peroxidation -- drug effects KW - Mice KW - Rats, Sprague-Dawley KW - Amyloid beta-Peptides -- genetics KW - Cells, Cultured KW - Hippocampus -- cytology KW - Cyclic AMP -- metabolism KW - Oxidative Stress -- drug effects KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Alzheimer Disease -- drug therapy KW - Neurons -- cytology KW - Alzheimer Disease -- etiology KW - Corticotropin-Releasing Hormone -- pharmacology KW - Corticotropin-Releasing Hormone -- genetics KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71021509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=Corticotropin-releasing+hormone+protects+neurons+against+insults+relevant+to+the+pathogenesis+of+Alzheimer%27s+disease.&rft.au=Pedersen%2C+W+A%3BMcCullers%2C+D%3BCulmsee%2C+C%3BHaughey%2C+N+J%3BHerman%2C+J+P%3BMattson%2C+M+P&rft.aulast=Pedersen&rft.aufirst=W&rft.date=2001-06-01&rft.volume=8&rft.issue=3&rft.spage=492&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=09699961&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reconstructing population history using JC virus: Amerinds, Spanish, and Africans in the ancestry of modern Puerto Ricans. AN - 71019942; 11459420 AB - The roots of the Hispanic populations of the Caribbean Islands and Central and South America go back to three continents of the Old World. In Puerto Rico major genetic contributions have come from (1) Asians in the form of the aboriginal Taino population, an Arawak tribe, present when Columbus arrived on the Island, (2) Europeans, largely Spanish explorers, settlers, government administrators, and soldiers, and (3) Africans who came as part of the slave trade. Since JC virus (JCV) genotypes characteristic of Asia, Europe, and Africa have been identified, and excretion of JCV in urine has been proposed as a marker for human migrations, we sought to characterize the JCV strains present in a Caribbean Hispanic population. We found that the strains of JCV present today in Puerto Rico are those derived from the Old World populations represented there: Types 1B and 4 from Spain, Types 3A, 3B, and 6 from Africa, and Type 2A from Asia. The Type 2A genotype represents the indigenous Taino people. This JCV genotype was represented much more frequently (61%) than would be predicted by the trihybrid model of genetic admixture. This might be attributable to characteristics of JCV Type 2A itself, as well as to the nature of the early relationships between Spanish men and native women. These findings indicate that the JCV strains carried by the Taino Indians can be found in today's Puerto Rican population despite the apparent demise of these people more than two centuries ago. Therefore, molecular characterization of JCV provides a tool to supplement genetic techniques for reconstructing population histories including admixed populations. JF - Human biology AU - Fernandez-Cobo, M AU - Jobes, D V AU - Yanagihara, R AU - Nerurkar, V R AU - Yamamura, Y AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 385 EP - 402 VL - 73 IS - 3 SN - 0018-7143, 0018-7143 KW - Index Medicus KW - Phylogeny KW - Genotype KW - Indians, Central American -- genetics KW - Puerto Rico KW - Spain KW - Humans KW - Adult KW - Africa KW - Middle Aged KW - Gene Pool KW - Male KW - Female KW - JC Virus -- genetics KW - Hispanic Americans -- genetics KW - Genetics, Population UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71019942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+biology&rft.atitle=Reconstructing+population+history+using+JC+virus%3A+Amerinds%2C+Spanish%2C+and+Africans+in+the+ancestry+of+modern+Puerto+Ricans.&rft.au=Fernandez-Cobo%2C+M%3BJobes%2C+D+V%3BYanagihara%2C+R%3BNerurkar%2C+V+R%3BYamamura%2C+Y%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Fernandez-Cobo&rft.aufirst=M&rft.date=2001-06-01&rft.volume=73&rft.issue=3&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Human+biology&rft.issn=00187143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression. AN - 71004350; 11432805 AB - The adaptor protein Grb2-associated binder-1 (Gab1) is known to bind to the SHP-2 tyrosine phosphatase on epidermal growth factor (EGF) receptor stimulation. To clarify the roles of these two proteins in EGF receptor (EGFR) signaling and determine their possible alteration during neoplastic cell progression, we studied these proteins in a Syrian hamster embryo (SHE) cell line model of neoplastic progression. Specifically, we used asbestos-transformed SHE fibroblasts: the 10W+8 clone, which is immortal but nontumorigenic; and the 10W2T clone, which is tumorigenic. Gab1 was detected, and the EGF-dependent formation of the EGFR-Gab1-SHP-2 complex was observed in 10W+8 cells. After cloning hamster Gab1 cDNA, exogenous expression of Gab1 significantly enhanced EGF-dependent mitogenic activity in 10W+8 cells. On the other hand, Gab1 was not detected in 10W2T cells, and the EGF-dependent association of SHP-2 with EGFR was also absent. Exogenous Gab1 expression in transfected 10W2T cells restored the EGF-dependent association of SHP-2 with EGFR, although it only showed a marginal effect on EGF-dependent mitogenic activity. Thus, Gab1 plays a pivotal role in the EGFR signaling pathway via the formation of the EGFR-Gab1-SHP-2 complex, and alteration in the expression and function of Gab1 is implicated in the neoplastic progression of SHE cells. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Kameda, H AU - Risinger, J I AU - Han, B B AU - Baek, S J AU - Barrett, J C AU - Glasgow, W C AU - Eling, T E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 307 EP - 318 VL - 12 IS - 6 SN - 1044-9523, 1044-9523 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - DNA, Complementary KW - GAB1 protein, human KW - Gab1 protein, mouse KW - Intracellular Signaling Peptides and Proteins KW - Mitogens KW - Phosphoproteins KW - Tyrosine KW - 42HK56048U KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - PTPN11 protein, human KW - EC 3.1.3.48 KW - PTPN6 protein, human KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Ptpn11 protein, mouse KW - Ptpn6 protein, mouse KW - Index Medicus KW - Mitogens -- pharmacology KW - Animals KW - Humans KW - Mice KW - Amino Acid Sequence KW - Mitogens -- metabolism KW - Epidermal Growth Factor -- pharmacology KW - Cloning, Molecular KW - Base Sequence KW - Tumor Cells, Cultured KW - Phosphorylation KW - Molecular Sequence Data KW - Mesocricetus KW - Tyrosine -- metabolism KW - Sequence Homology, Amino Acid KW - Epidermal Growth Factor -- metabolism KW - Cell Division KW - Cricetinae KW - Receptor, Epidermal Growth Factor -- metabolism KW - Phosphoproteins -- genetics KW - Protein Tyrosine Phosphatases -- metabolism KW - Phosphoproteins -- physiology KW - Protein Tyrosine Phosphatases -- physiology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71004350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Identification+of+epidermal+growth+factor+receptor-+Grb2-associated+binder-1-SHP-2+complex+formation+and+its+functional+loss+during+neoplastic+cell+progression.&rft.au=Kameda%2C+H%3BRisinger%2C+J+I%3BHan%2C+B+B%3BBaek%2C+S+J%3BBarrett%2C+J+C%3BGlasgow%2C+W+C%3BEling%2C+T+E&rft.aulast=Kameda&rft.aufirst=H&rft.date=2001-06-01&rft.volume=12&rft.issue=6&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-07-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AJ250669; GENBANK; U43885 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characteristics of patients with hypnotic-related psychiatric disorders in the nationwide mental hospital survey. AN - 70982762; 11422843 AB - We investigated the characteristics of patients with hypnotic-related psychiatric disorders. Subjects were 90 patients reported in the nationwide Mental Hospital Survey in 1998, who were divided into three groups according to their history of substances use. Group A (patients without history of any illicit substance use) was estimated to be the most common and core group with iatrogenic characteristics. Hypnotic use in Group B (patients with history of any illicit substance use) was recognized as one of behavioral disorders in the psychosocial context. Patients in Group C (patients with multiple-substance use and without history of any illicit substance use) showed the most serious disorders in the context of addiction. More specified treatment programs would be required considering patients' characteristics. JF - Psychiatry and clinical neurosciences AU - Ozaki, S AU - Kikuchi, S AU - Wada, K AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology, Ichikawa-shi, Japan. ozaki@ncnp-k.go.jp Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 205 EP - 207 VL - 55 IS - 3 SN - 1323-1316, 1323-1316 KW - Hypnotics and Sedatives KW - 0 KW - Index Medicus KW - Japan -- epidemiology KW - Humans KW - Adult KW - Alcoholism -- psychology KW - Male KW - Hospitals, Psychiatric KW - Female KW - Mental Disorders -- epidemiology KW - Mental Disorders -- chemically induced KW - Health Surveys KW - Mental Disorders -- etiology KW - Hypnotics and Sedatives -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70982762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+and+clinical+neurosciences&rft.atitle=Characteristics+of+patients+with+hypnotic-related+psychiatric+disorders+in+the+nationwide+mental+hospital+survey.&rft.au=Ozaki%2C+S%3BKikuchi%2C+S%3BWada%2C+K&rft.aulast=Ozaki&rft.aufirst=S&rft.date=2001-06-01&rft.volume=55&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Psychiatry+and+clinical+neurosciences&rft.issn=13231316&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Commitment of the National Institute of Environmental Health Sciences to community-based participatory research for rural health. AN - 70978551; 11427398 AB - The National Institute of Environmental Health Sciences (NIEHS) is the leading biomedical research institution in the United States whose mission is to support research that seeks to understand how environmental exposures affect human health. NIEHS possesses a longstanding interest in the health effects of agrochemical and other environmental exposures in rural America, including pesticides, to farmers and their families and to migrant farmworkers and their families. In recent years, NIEHS has begun augmenting traditional basic science investigations with innovative programs that translate findings from the laboratory to affected populations. It is through community-based participatory research that NIEHS strives to advance the public health field by fostering the development of culturally relevant interventions that will reduce exposures to environmental contaminants and the risk of environmentally induced disease. In this article, we describe the translational research program at NIEHS as it relates to the NIEHS mission and highlight activities pertinent to the health of rural communities, especially underserved populations. We provide an overview of NIEHS-supported projects addressing health concerns of Native American and rural African-American communities in addition to farmworkers. We conclude with a discussion of future plans for community-based participatory research at NIEHS. JF - Environmental health perspectives AU - O'Fallon, L R AU - Dearry, A AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. ofallon@niehs.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 469 EP - 473 VL - 109 Suppl 3 SN - 0091-6765, 0091-6765 KW - Pesticides KW - 0 KW - Index Medicus KW - United States KW - Occupational Exposure KW - Cultural Characteristics KW - Indians, North American KW - Minority Groups KW - Rural Population KW - Humans KW - Medically Underserved Area KW - Organizational Objectives KW - Emigration and Immigration KW - Agriculture KW - Environmental Health KW - National Institutes of Health (U.S.) KW - Community-Institutional Relations KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70978551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Commitment+of+the+National+Institute+of+Environmental+Health+Sciences+to+community-based+participatory+research+for+rural+health.&rft.au=O%27Fallon%2C+L+R%3BDearry%2C+A&rft.aulast=O%27Fallon&rft.aufirst=L&rft.date=2001-06-01&rft.volume=109+Suppl+3&rft.issue=&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Public Health Rep. 1999 Sep-Oct;114(5):459-68 [10590768] Health Educ Behav. 1999 Aug;26(4):563-78 [10435238] Health Place. 1999 Dec;5(4):259-70 [10984580] J Expo Anal Environ Epidemiol. 2000 Nov-Dec;10(6 Pt 2):630-7 [11138655] Environ Health Perspect. 2001 Jun;109 Suppl 3:429-34 [11427392] Environ Health Perspect. 2001 Jun;109 Suppl 3:449-55 [11427395] Environ Health Perspect. 2001 Jun;109 Suppl 3:461-8 [11427397] Pharmacol Ther. 1980;8(2):379-475 [6992159] J Toxicol Clin Toxicol. 1982 Aug;19(6-7):609-21 [7161848] Annu Rev Pharmacol Toxicol. 1984;24:19-42 [6375545] Environ Health Perspect. 1995 Sep;103 Suppl 6:127-30 [8549459] Environ Health Perspect. 1996 Apr;104(4):362-9 [8732939] Environ Health Perspect. 1998 Jul;106(7):415-20 [9637799] Environ Health Perspect. 1998 Jun;106 Suppl 3:849-55 [9646048] Environ Health Perspect. 1999 Jun;107 Suppl 3:409-19 [10346990] Environ Health Perspect. 2000 Mar;108(3):233-8 [10706529] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of galectin-10 (eosinophil Charcot-Leyden crystal protein): a GC box (-44 to -50) controls butyric acid induction of gene expression. AN - 70976910; 11441910 AB - Galectin-10 (gal-10, also known as Charcot-Leyden crystal protein) is a member of the galectin family of beta-galactoside binding proteins that is expressed uniquely in eosinophilic and basophilic leukocytes. To gain a better understanding of galectin gene expression, we present an analysis of the transcriptional regulation of the gene encoding gal-10. Analysis of the minimal promoter revealed nine consensus-binding sites for transcription factors, including several that are also found in the minimal promoters of galectins -1, -2, and -3. The decrease in gal-10 promoter activity after disruption of either the GC box (-44 to -50) or the Oct site (-255 to -261) suggests that these sites, along with the previously characterized GATA and EoTF sites, are necessary for full promoter activity. By supershift analysis, we demonstrate binding of the transcription factors Sp1 and Oct1 to the consensus GC box and the Oct site, respectively. Similar to gal-1, gal-10 expression is induced by butyric acid, an effect that is lost upon ablation of the GC box. Additionally, we demonstrate AML3 binding to the consensus AML site and YY1 binding to the Inr sequence, both elements functioning as silencers in the gal-10 promoter. JF - Life sciences AU - Dyer, K D AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 201 EP - 212 VL - 69 IS - 2 SN - 0024-3205, 0024-3205 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Erythroid-Specific DNA-Binding Factors KW - Glycoproteins KW - Membrane Proteins KW - Neoplasm Proteins KW - Nuclear Proteins KW - Organic Cation Transporter 1 KW - Transcription Factors KW - YY1 Transcription Factor KW - YY1 protein, human KW - Butyric Acid KW - 107-92-6 KW - Lysophospholipase KW - EC 3.1.1.5 KW - lysolecithin acylhydrolase KW - Index Medicus KW - Nuclear Proteins -- genetics KW - Carrier Proteins -- metabolism KW - Transcription Factors -- metabolism KW - HL-60 Cells KW - Carrier Proteins -- genetics KW - Humans KW - Membrane Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Transcription, Genetic KW - Membrane Proteins -- genetics KW - Transcription Factors -- genetics KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Butyric Acid -- pharmacology KW - Promoter Regions, Genetic KW - Glycoproteins -- metabolism KW - Eosinophils -- metabolism KW - Gene Expression Regulation KW - Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70976910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Transcriptional+regulation+of+galectin-10+%28eosinophil+Charcot-Leyden+crystal+protein%29%3A+a+GC+box+%28-44+to+-50%29+controls+butyric+acid+induction+of+gene+expression.&rft.au=Dyer%2C+K+D%3BRosenberg%2C+H+F&rft.aulast=Dyer&rft.aufirst=K&rft.date=2001-06-01&rft.volume=69&rft.issue=2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity. AN - 70972021; 11432713 AB - Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China. In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine. In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial. Compliance rates were 93% and 92.9% for 39 months of treatment with the vitamins/mineral and garlic preparation, respectively. The means for serum concentrations of vitamins C and E were 7.2 microg/ml and 1695 microg/dl among subjects in the active treatment groups compared with 3.1 microg/ml and 752 microg/dl among subjects in the placebo treatment group, respectively. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment groups during the 39-month trial period. JF - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) AU - You, W C AU - Chang, Y S AU - Heinrich, J AU - Ma, J L AU - Liu, W D AU - Zhang, L AU - Brown, L M AU - Yang, C S AU - Gail, M H AU - Fraumeni, J F AU - Xu, G W AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892, USA. youw@exchange.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 257 EP - 263 VL - 10 IS - 3 SN - 0959-8278, 0959-8278 KW - Antioxidants KW - 0 KW - Penicillins KW - beta Carotene KW - 01YAE03M7J KW - Vitamin E KW - 1406-18-4 KW - Amoxicillin KW - 804826J2HU KW - Selenium KW - H6241UJ22B KW - Omeprazole KW - KG60484QX9 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Phytotherapy KW - Helicobacter pylori KW - Ascorbic Acid -- therapeutic use KW - Double-Blind Method KW - Plants, Medicinal KW - Humans KW - Vitamin E -- therapeutic use KW - Aged KW - Drug Therapy, Combination KW - Amoxicillin -- therapeutic use KW - Selenium -- therapeutic use KW - beta Carotene -- therapeutic use KW - Patient Compliance KW - China -- epidemiology KW - Adult KW - Treatment Outcome KW - Omeprazole -- therapeutic use KW - Garlic -- therapeutic use KW - Middle Aged KW - Female KW - Male KW - Prevalence KW - Precancerous Conditions -- microbiology KW - Helicobacter Infections -- drug therapy KW - Helicobacter Infections -- microbiology KW - Precancerous Conditions -- drug therapy KW - Penicillins -- therapeutic use KW - Stomach Neoplasms -- prevention & control KW - Helicobacter Infections -- epidemiology KW - Precancerous Conditions -- epidemiology KW - Stomach Neoplasms -- drug therapy KW - Stomach Neoplasms -- microbiology KW - Antioxidants -- therapeutic use KW - Precancerous Conditions -- prevention & control KW - Stomach Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70972021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.atitle=An+intervention+trial+to+inhibit+the+progression+of+precancerous+gastric+lesions%3A+compliance%2C+serum+micronutrients+and+S-allyl+cysteine+levels%2C+and+toxicity.&rft.au=You%2C+W+C%3BChang%2C+Y+S%3BHeinrich%2C+J%3BMa%2C+J+L%3BLiu%2C+W+D%3BZhang%2C+L%3BBrown%2C+L+M%3BYang%2C+C+S%3BGail%2C+M+H%3BFraumeni%2C+J+F%3BXu%2C+G+W&rft.aulast=You&rft.aufirst=W&rft.date=2001-06-01&rft.volume=10&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.issn=09598278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial of carboxyamido-triazole and paclitaxel for relapsed solid tumors: potential efficacy of the combination and demonstration of pharmacokinetic interaction. AN - 70966640; 11410496 AB - Preclinical and clinical investigation of the combination of the antiangiogenesis/anti-invasion agent carboxyamido-triazole (CAI) administered with the cytotoxic agent paclitaxel (PAX). Colony-forming assays were used to test the activity of CAI plus PAX on A2780 human ovarian cancer. The sequence of CAI followed by PAX (CAI>Pax) was modeled in nude mice to test for potential additive toxicity. The Phase I clinical dose escalation schema tested p.o. administered CAI in PEG-400 (50-100 mg/m(2)) or micronized CAI (250 mg/m(2)) for 8 days followed by a 3-h infusion of PAX (110-250 mg/m(2)) every 21 days. Patients were assessed for toxicity, pharmacokinetics of CAI and PAX, and disease outcome. In preclinical studies, CAI>Pax was additive in A2780 human ovarian cancer cell lines when CAI (1 or 5 microM) preceded subtherapeutic doses of PAX. CAI did not reverse PAX resistance and collateral resistance to CAI was documented in PAX-resistant cells. CAI>PAX administration had no overt additive toxicity in nude mice. Thirty-nine patients were treated on a dose-escalation Phase I trial using daily oral CAI for 8 days followed by the PAX infusion. Pharmacokinetic analysis revealed that PAX caused an acute increase in circulating CAI concentrations in a dose-dependent fashion. No additive or cumulative toxicity was observed, and grade 3 nonhematological toxicity was rare. Three partial responses and two minor responses were observed. The sequential combination of CAI and PAX is well tolerated, and the activity observed suggests that further study of the combination is warranted. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kohn, E C AU - Reed, E AU - Sarosy, G A AU - Minasian, L AU - Bauer, K S AU - Bostick-Bruton, F AU - Kulpa, V AU - Fuse, E AU - Tompkins, A AU - Noone, M AU - Goldspiel, B AU - Pluda, J AU - Figg, W D AU - Liotta, L A AD - Medicine Branch, National Cancer Institute, and Warren G. Magnuson Clinical Center, NIH, Bethesda, Maryland 20892, USA. eckohn@helix.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1600 EP - 1609 VL - 7 IS - 6 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Antineoplastic Agents -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Mice, Nude KW - Mice KW - Ovarian Neoplasms -- drug therapy KW - Tumor Cells, Cultured KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Neovascularization, Pathologic KW - Inhibitory Concentration 50 KW - Antineoplastic Agents -- therapeutic use KW - Time Factors KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Male KW - Paclitaxel -- administration & dosage KW - Neoplasms -- drug therapy KW - Drug Interactions KW - Paclitaxel -- therapeutic use KW - Triazoles -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Recurrence KW - Triazoles -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70966640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+trial+of+carboxyamido-triazole+and+paclitaxel+for+relapsed+solid+tumors%3A+potential+efficacy+of+the+combination+and+demonstration+of+pharmacokinetic+interaction.&rft.au=Kohn%2C+E+C%3BReed%2C+E%3BSarosy%2C+G+A%3BMinasian%2C+L%3BBauer%2C+K+S%3BBostick-Bruton%2C+F%3BKulpa%2C+V%3BFuse%2C+E%3BTompkins%2C+A%3BNoone%2C+M%3BGoldspiel%2C+B%3BPluda%2C+J%3BFigg%2C+W+D%3BLiotta%2C+L+A&rft.aulast=Kohn&rft.aufirst=E&rft.date=2001-06-01&rft.volume=7&rft.issue=6&rft.spage=1600&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CTNNB1 mutations and beta-catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1. AN - 70962128; 11429783 AB - beta-Catenin plays a key role in the Wnt signaling pathway, and mutations of CTNNB1, the gene that encodes beta-catenin, have been identified in about one-fourth of human hepatocellular carcinomas from regions of low aflatoxin B1 exposure. In this study 62 hepatocellular carcinomas (HCCs) from people highly exposed to aflatoxin B1 in Guangxi, People's Republic of China, were laser-capture microdissected and examined for CTNNB1 mutations. In addition, 41 of the HCCs were evaluated for the presence of the beta-catenin protein by immunohistochemical methods. Twenty of the HCCs showed positive results for beta-catenin, with strong membrane staining, while adjacent non-neoplastic liver tissue lacked or showed only weak membrane staining. One HCC, in which a CTNNB1 mutation was not detected, showed nuclear staining for the beta-catenin protein. Mutations of CTNNB1 were identified in five HCCs. These consisted of four point mutations in the glycogen serine kinase-3beta phosphorylation region of codons 32-45 and one deletion of codons 32-38. These mutations were similar to those previously reported for human HCC, although at a lower frequency. A signature mutation profile associated with aflatoxin B1 exposure could not be identified. The immunohistochemical findings indicate a role for accumulation of beta-catenin and possibly increased Wnt signaling in aflatoxin B1-associated HCC. The low frequency of CTNNB1 mutations, however, suggests that mutation of another Wnt signaling component, such as the Wnt scaffolding protein axin or the adenomatous polyposis coli protein, both of which modulate beta-catenin stability, also may be involved in aflatoxin-associated HCC. Published 2001 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Devereux, T R AU - Stern, M C AU - Flake, G P AU - Yu, M C AU - Zhang, Z Q AU - London, S J AU - Taylor, J A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 68 EP - 73 VL - 31 IS - 2 SN - 0899-1987, 0899-1987 KW - CTNNB1 protein, human KW - 0 KW - Codon KW - Cytoskeletal Proteins KW - Trans-Activators KW - beta Catenin KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Exons KW - DNA Mutational Analysis KW - Humans KW - Aged KW - Polymorphism, Single-Stranded Conformational KW - Infant KW - Adult KW - Genes, p53 -- genetics KW - Middle Aged KW - Immunohistochemistry KW - Signal Transduction KW - Female KW - Male KW - Cytoskeletal Proteins -- biosynthesis KW - Aflatoxin B1 -- metabolism KW - Carcinoma, Hepatocellular -- genetics KW - Mutation KW - Liver Neoplasms -- genetics KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70962128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=CTNNB1+mutations+and+beta-catenin+protein+accumulation+in+human+hepatocellular+carcinomas+associated+with+high+exposure+to+aflatoxin+B1.&rft.au=Devereux%2C+T+R%3BStern%2C+M+C%3BFlake%2C+G+P%3BYu%2C+M+C%3BZhang%2C+Z+Q%3BLondon%2C+S+J%3BTaylor%2C+J+A&rft.aulast=Devereux&rft.aufirst=T&rft.date=2001-06-01&rft.volume=31&rft.issue=2&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Propionyl-L-carnitine as protector against adriamycin-induced cardiomyopathy. AN - 70955372; 11419959 AB - Propionyl- l -carnitine (PLC) is a naturally occurring compound that has been considered for the treatment of many forms of cardiomyopathies. In this study, the possible mechanisms whereby PLC could protect against adriamycin (ADR)-induced cardiomyopathy were carried out. Administration of ADR (3 mg kg(-1)i.p., every other day over a period of 2 weeks) resulted in a significant two-fold increase in serum levels of creatine phosphokinase, lactate dehydrogenase and glutamic oxaloacetic transaminase, whereas daily administration of PLC (250 mg kg(-1), i.p. for 2 weeks) induced non-significant change. Daily administration of PLC to ADR-treated rats resulted in complete reversal of ADR-induced increase in cardiac enzymes except lactate dehydrogenase which was only reversed by 66%. In cardiac tissue homogenate, ADR caused a significant 53% increase in malonedialdehyde (MDA) and a significant 50% decrease in reduced glutathione (GSH) levels, whereas PLC induced a significant 33% decrease in MDA and a significant 41% increase in GSH levels. Daily administration of PLC to ADR-treated rats completely reversed the increase in MDA and the decrease in GSH induced by ADR to the normal levels. In rat heart mitochondria isolated 24 h after the last dose, ADR induced a significant 48% and 42% decrease in(14)CO(2)released from the oxidation of [1-(14)C]palmitoyl-CoA and [1-(14)C]palmitoylcarnitine, respectively, whereas PLC resulted in a significant 66% and 54% increase in the oxidation of both substrates, respectively. Interestingly, administration of PLC to ADR-treated rats resulted in complete recovery of the ADR-induced decrease in the oxidation of both substrates. In addition, in rat heart mitochondria, the oxidation of [1-(14)C]pyruvate, [1-(14)C]pyruvate and [1-(14)C]octanoate were not affected by ADR and/or PLC treatment. Moreover, ADR caused severe histopathological lesions manifested as toxic myocarditis which is protected by PLC. Worth mentioning is that PLC had no effect on the antitumour activity of ADR in solid Ehrlich carcinoma. Results from this study suggest that: (1) in the heart, PLC therapy completely protects against ADR-induced inhibition of mitochondrial beta -oxidation of long-chain fatty acids; (2) PLC has and/or induces a powerful antioxidant defense mechanism against ADR-induced lipid peroxidation of cardiac membranes; and finally (3) PLC has no effect on the antitumour activity of ADR. Copyright 2001 Academic Press. JF - Pharmacological research AU - Sayed-Ahmed, M M AU - Salman, T M AU - Gaballah, H E AU - Abou El-Naga, S A AU - Nicolai, R AU - Calvani, M AD - Pharmacology Unit, National Cancer Institute, Fum El-Khalig, Kasr El-Aini Street, Cairo, Egypt. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 513 EP - 520 VL - 43 IS - 6 SN - 1043-6618, 1043-6618 KW - Antineoplastic Agents KW - 0 KW - Cardiotonic Agents KW - propionylcarnitine KW - 17298-37-2 KW - Malondialdehyde KW - 4Y8F71G49Q KW - Doxorubicin KW - 80168379AG KW - Glutathione KW - GAN16C9B8O KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - Animals KW - Glutathione -- metabolism KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Mice KW - Rats KW - Malondialdehyde -- metabolism KW - Oxidation-Reduction KW - Rats, Sprague-Dawley KW - Carcinoma, Ehrlich Tumor -- metabolism KW - In Vitro Techniques KW - Mitochondria, Heart -- drug effects KW - Mitochondria, Heart -- metabolism KW - Female KW - Male KW - Cardiomyopathies -- prevention & control KW - Antineoplastic Agents -- toxicity KW - Cardiotonic Agents -- therapeutic use KW - Doxorubicin -- toxicity KW - Carnitine -- analogs & derivatives KW - Cardiomyopathies -- chemically induced KW - Carnitine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70955372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=Propionyl-L-carnitine+as+protector+against+adriamycin-induced+cardiomyopathy.&rft.au=Sayed-Ahmed%2C+M+M%3BSalman%2C+T+M%3BGaballah%2C+H+E%3BAbou+El-Naga%2C+S+A%3BNicolai%2C+R%3BCalvani%2C+M&rft.aulast=Sayed-Ahmed&rft.aufirst=M&rft.date=2001-06-01&rft.volume=43&rft.issue=6&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=10436618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secondary partial empty sella syndrome in an elite bodybuilder. AN - 70954714; 11428511 AB - The pituitary gland is a hormone-responsive gland and is known to vary in size depending on the hormonal status of the patient and the multifaceted positive and negative feedback hypothalamic-pituitary-gonadal axis. Partial empty sella syndrome with an atrophied pituitary gland is seen in primary neuroendocrinopathies such as growth hormone deficiency, primary hypothyroidism, central diabetes insipidus and hypogonadism. Partial empty sella has also been shown to occur in patients with elevations in intracranial pressure. Secondary partial empty sella syndrome with significant pituitary gland atrophy from negative feedback inhibition of long-term exogenous hormonal use has not been previously reported. We are reporting on a case of partial empty sella syndrome occurring in an elite bodybuilder with a long history of exogenous abuse of growth hormone, testosterone and thyroid hormone. The pathophysiological mechanisms of secondary partial empty sella syndrome from exogenous hormone use and the possibility for elevations in intracranial pressure contributing to this syndrome will be discussed. JF - Neurological research AU - Dickerman, R D AU - Jaikumar, S AD - National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Surgical Neurology Branch, Bethesda, MD, USA. drrdd@yahoo.com Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 336 EP - 338 VL - 23 IS - 4 SN - 0161-6412, 0161-6412 KW - Anabolic Agents KW - 0 KW - Index Medicus KW - Self Administration KW - Humans KW - Adult KW - Feedback KW - Time Factors KW - Male KW - Empty Sella Syndrome -- chemically induced KW - Weight Lifting KW - Anabolic Agents -- administration & dosage KW - Anabolic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70954714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurological+research&rft.atitle=Secondary+partial+empty+sella+syndrome+in+an+elite+bodybuilder.&rft.au=Dickerman%2C+R+D%3BJaikumar%2C+S&rft.aulast=Dickerman&rft.aufirst=R&rft.date=2001-06-01&rft.volume=23&rft.issue=4&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=Neurological+research&rft.issn=01616412&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperthermia and hypoxia: new developments in anticancer chemotherapy. AN - 70948865; 11417976 AB - It has been demonstrated in vitro and in vivo that hyperthermia can enhance the cytotoxicity of some chemotherapeutic agents. The in vivo studies have demonstrated that the thermal advantage is maximized at mild temperatures such as at 40.5--43 degrees C. Thermo-chemotherapy is widely applied in limb perfusion and intraperitoneal chemotherapy. Hypoxia in solid tumours leads to resistance to most anticancer drugs and appears to accelerate malignant progression and increase metastasis. The recent development of new drugs highly toxic to hypoxic cells may bring new strategies in anticancer treatments and move this condition from being a problem to a new tool in cancer control. Copyright Harcourt Publishers Limited. JF - European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology AU - Zaffaroni, N AU - Fiorentini, G AU - De Giorgi, U AD - Department of Experimental Oncology, National Cancer Institute of Milano, Italy. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 340 EP - 342 VL - 27 IS - 4 SN - 0748-7983, 0748-7983 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Antineoplastic Agents -- administration & dosage KW - Hyperthermia, Induced KW - Cell Hypoxia -- drug effects KW - Chemotherapy, Cancer, Regional Perfusion -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70948865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+surgical+oncology+%3A+the+journal+of+the+European+Society+of+Surgical+Oncology+and+the+British+Association+of+Surgical+Oncology&rft.atitle=Hyperthermia+and+hypoxia%3A+new+developments+in+anticancer+chemotherapy.&rft.au=Zaffaroni%2C+N%3BFiorentini%2C+G%3BDe+Giorgi%2C+U&rft.aulast=Zaffaroni&rft.aufirst=N&rft.date=2001-06-01&rft.volume=27&rft.issue=4&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=European+journal+of+surgical+oncology+%3A+the+journal+of+the+European+Society+of+Surgical+Oncology+and+the+British+Association+of+Surgical+Oncology&rft.issn=07487983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Eur J Surg Oncol. 2002 Feb;28(1):95 [11869025] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paradoxical effects of platelet-derived growth factor-A overexpression in malignant mesothelioma. Antiproliferative effects in vitro and tumorigenic stimulation in vivo. AN - 70943392; 11415934 AB - Malignant mesothelioma is associated with asbestos exposure and remains resistant to all therapeutic intervention. Previous studies have suggested an enhancing role for platelet-derived growth factor (PDGF) in mesothelial tumorigenicity, although the mechanism by which PDGF facilitates tumorigenicity is unknown. Here, we evaluate the contribution of PDGF-A expression to mesothelial tumorigenicity using ectopic modulation of PDGF-A expression. We find, in accordance with other reports, that the receptor for PDGF-A, although expressed at high levels in normal human mesothelial cells, is not easily detectable in mesothelioma. Further, we show that PDGF-A overexpression is responsible for autocrine downregulation of its receptor. Our data indicate, surprisingly, that for mesothelioma cells in vitro, high-level activation of a PDGF-A-PDGF receptor loop is antiproliferative whereas abrogation of PDGF-A expression stimulates growth. These data suggest that PDGF-A does not contribute to tumorigenicity by autocrine stimulation of proliferation. In contrast, increased PDGF-A expression in vivo increases tumor incidence and growth rate and decreases the latency period to tumor formation whereas abrogation of PDGF-A expression decreases tumor incidence and increases latency. Thus, the tumorigenic effect of PDGF-A must act through paracrine mechanisms relevant at early stages of tumor initiation. JF - American journal of respiratory cell and molecular biology AU - Metheny-Barlow, L J AU - Flynn, B AU - van Gijssel, H E AU - Marrogi, A AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis; and Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland, USA. ljm@gunet.georgetown.edu Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 694 EP - 702 VL - 24 IS - 6 SN - 1044-1549, 1044-1549 KW - Platelet-Derived Growth Factor KW - 0 KW - platelet-derived growth factor A KW - Receptor, Platelet-Derived Growth Factor alpha KW - EC 2.7.10.1 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Receptor, Platelet-Derived Growth Factor alpha -- biosynthesis KW - Paracrine Communication KW - Down-Regulation KW - Humans KW - Autocrine Communication KW - Mice, Nude KW - Mice KW - Mesothelioma -- etiology KW - Platelet-Derived Growth Factor -- biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70943392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Paradoxical+effects+of+platelet-derived+growth+factor-A+overexpression+in+malignant+mesothelioma.+Antiproliferative+effects+in+vitro+and+tumorigenic+stimulation+in+vivo.&rft.au=Metheny-Barlow%2C+L+J%3BFlynn%2C+B%3Bvan+Gijssel%2C+H+E%3BMarrogi%2C+A%3BGerwin%2C+B+I&rft.aulast=Metheny-Barlow&rft.aufirst=L&rft.date=2001-06-01&rft.volume=24&rft.issue=6&rft.spage=694&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells. AN - 70940718; 11417480 AB - Many chemotherapeutic agents induce apoptosis in tumor cells, but killing of normal cells remains a major obstacle. Development of multidrug resistance further limits chemotherapy in cancer. Here, I show that multidrug resistance can be exploited for selective killing of multidrug-resistant cells by a combination of an apoptosis-inducing agent that is not a substrate of either Pgp or MRP (e.g. flavopiridol) with a caspase inhibitor that is a substrate (e.g. Z-DEVD-fmk). In normal cells, treatment with caspase inhibitors prevented PARP cleavage, nuclear fragmentation, and cell death caused by flavopiridol or epothilone B. In contrast, Pgp- and MRP-expressing cells were not rescued by caspase inhibitors. Furthermore, reversal of drug resistance renders Pgp cells sensitive to caspase inhibitors abolishing therapeutic advantage. Thus, caspase inhibitors, that are inactive in multidrug-resistant cells, protect normal but not multidrug-resistant cells against chemotherapy, permitting selective eradication of multidrug-resistant cells. Clinical application of this approach may diminish the toxic side-effects of chemotherapy in patients with multidrug-resistant tumors. JF - Leukemia AU - Blagosklonny, M V AD - Medicine Branch, National Cancer Institute, Building 10, R 12N226 NIH, Bethesda, MD 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 936 EP - 941 VL - 15 IS - 6 SN - 0887-6924, 0887-6924 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Antineoplastic Agents KW - Boronic Acids KW - Cyclosporins KW - Cysteine Proteinase Inhibitors KW - Epothilones KW - Epoxy Compounds KW - Flavonoids KW - Multidrug Resistance-Associated Proteins KW - Neoplasm Proteins KW - Oligopeptides KW - P-Glycoprotein KW - Piperidines KW - Pyrazines KW - Thiazoles KW - benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone KW - benzoylcarbonyl-valyl-aspartyl-valyl-alanyl-aspartyl-fluoromethyl ketone KW - benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone KW - benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - alvocidib KW - 45AD6X575G KW - Bortezomib KW - 69G8BD63PP KW - Doxorubicin KW - 80168379AG KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Paclitaxel KW - P88XT4IS4D KW - valspodar KW - Q7ZP55KF3X KW - epothilone B KW - UEC0H0URSE KW - Index Medicus KW - Boronic Acids -- pharmacology KW - Cysteine Endopeptidases -- physiology KW - Jurkat Cells -- metabolism KW - Humans KW - Paclitaxel -- pharmacology KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Hematopoietic Stem Cells -- drug effects KW - Jurkat Cells -- drug effects KW - Doxorubicin -- pharmacology KW - Cell Survival -- drug effects KW - Flavonoids -- pharmacology KW - DNA Fragmentation KW - Pyrazines -- pharmacology KW - Cyclosporins -- pharmacology KW - Thiazoles -- pharmacology KW - Piperidines -- pharmacology KW - HL-60 Cells -- drug effects KW - HL-60 Cells -- metabolism KW - Epoxy Compounds -- pharmacology KW - Oligopeptides -- pharmacology KW - Substrate Specificity KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Cell Cycle -- drug effects KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- antagonists & inhibitors KW - P-Glycoprotein -- metabolism KW - ATP-Binding Cassette Transporters -- metabolism KW - Apoptosis -- drug effects KW - Drug Resistance, Neoplasm KW - Neoplasm Proteins -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70940718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Treatment+with+inhibitors+of+caspases%2C+that+are+substrates+of+drug+transporters%2C+selectively+permits+chemotherapy-induced+apoptosis+in+multidrug-resistant+cells+but+protects+normal+cells.&rft.au=Blagosklonny%2C+M+V&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2001-06-01&rft.volume=15&rft.issue=6&rft.spage=936&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences between the mutational consequences of replication of cis- and trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-deoxyguanosine adducts in M13mp7L2 constructs. AN - 70936520; 11409943 AB - The four adducts at N(2) of deoxyguanosine derived from cis-opening at C-10 of four optically active isomers of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene were incorporated into 5'-TTCGAATCCTTCCCCC [context III(G)] and 5'-GGGGTTCCCGAGCGGC [context IV(G)] at the underlined site. The mutagenic consequences of these lesions in each of the two sequence contexts were examined after ligation of the modified oligonucleotides into single-stranded M13mp7L2 and replication of the vector in SOS-induced Escherichia coli. Total frequencies of base substitution mutations ranged between 14 and 48%. The mutation frequencies were generally higher in context IV(G) than in context III(G), and consisted mainly of G-->T followed by G-->C base substitutions. A substantial number of deletions or insertions of one guanine was also found for all adducts in context IV(G), where the adduct is located at the 3'-end of a run of five guanines. The overall frequencies of base substitution mutations induced by cis-opened adducts were substantially higher than those observed with the trans-opened dGuo adducts in the same sequences [Page et al. (1998) Biochemistry 37, 9127-9137]. Although G-->T base substitutions predominated for both the cis- and trans-opened adducts, the cis-opened dGuo adducts generally resulted in a higher proportion of G-->C [particularly in context III(G)] relative to G-->A, whereas the opposite was true for the trans-opened dGuo adducts. The present results along with previous data indicate that mutagenicity is highly dependent on a combination of sequence context and adduct stereochemistry. JF - Chemical research in toxicology AU - Pontén, I AU - Kroth, H AU - Sayer, J M AU - Dipple, A AU - Jerina, D M AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 720 EP - 726 VL - 14 IS - 6 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - DNA Adducts KW - Benzo(a)pyrene KW - 3417WMA06D KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Mutagenicity Tests KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Isomerism KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Chromatography, High Pressure Liquid KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- adverse effects KW - Carcinogens -- chemistry KW - Benzo(a)pyrene -- chemistry KW - Benzo(a)pyrene -- adverse effects KW - Deoxyguanosine -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Amino Acid Substitution KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70936520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Differences+between+the+mutational+consequences+of+replication+of+cis-+and+trans-opened+benzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide-deoxyguanosine+adducts+in+M13mp7L2+constructs.&rft.au=Pont%C3%A9n%2C+I%3BKroth%2C+H%3BSayer%2C+J+M%3BDipple%2C+A%3BJerina%2C+D+M&rft.aulast=Pont%C3%A9n&rft.aufirst=I&rft.date=2001-06-01&rft.volume=14&rft.issue=6&rft.spage=720&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The P-glycoprotein antagonist PSC 833 increases the plasma concentrations of 6alpha-hydroxypaclitaxel, a major metabolite of paclitaxel. AN - 70932628; 11410497 AB - Overexpression of P-glycoprotein (Pgp) is one mechanism of drug resistance in cancer chemotherapy. A Phase I trial was conducted using PSC 833, a Pgp antagonist, in combination with paclitaxel in patients with refractory cancer. The objective of this study was to assess the effect of PSC 833 on the metabolism of paclitaxel and characterize the differences in 6alpha-hydroxypaclitaxel pharmacokinetics. In addition, we examined the possibility of enhanced cytotoxicity of paclitaxel by the coexistence of 6alpha-hydroxypaclitaxel. Patients received paclitaxel 35 mg/m(2)/day by continuous intravenous infusion (CIVI) x 4 days without PSC 833 in cycle 1 and escalating doses of paclitaxel (13.1, 17.5, or 21.3 mg/m(2)/day CIVI x 4 days) with 5 mg/kg PSC 833 by mouth every 6 h x 7 days in cycle 2. Plasma samples were analyzed for both paclitaxel and its major metabolite with high-performance liquid chromatography methods. Using human liver microsomes, we studied the effect of PSC 833 on the metabolism of paclitaxel. In addition, the in vitro cytotoxicity of 6alpha-hydroxypaclitaxel alone and in combination with paclitaxel was evaluated. Twenty-one of 22 patients had a metabolite peak (6alpha-hydroxypaclitaxel) observed in the chromatogram of plasma samples from cycle 2 when they received paclitaxel in combination with PSC 833. This metabolite was not detectable in plasma obtained during the first cycle when they received paclitaxel without PSC 833. During cycle 2, the mean concentrations of 6alpha-hydroxypaclitaxel and paclitaxel were 0.10 +/- 0.074 and 0.079 +/- 0.041 microg/ml, respectively. A moderate association was observed between total bilirubin and 6alpha-hydroxypaclitaxel concentrations (P = 0.015, r = 0.52; n = 21). Human liver microsome experiments showed that a PSC 833 concentration as high as 10 microM did not affect the production of 6alpha-hydroxypaclitaxel. Paclitaxel cytotoxicity in HL60 and K562 human leukemia cells was increased in the presence of noncytotoxic concentrations of 6alpha-hydroxypaclitaxel. PSC 833 increases the plasma concentration of 6alpha-hydroxypaclitaxel during paclitaxel therapy. Inhibition of cytochrome P-450 3A4 by PSC 833 may explain this in part, although other mechanisms cannot be excluded. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kang, M H AU - Figg, W D AU - Ando, Y AU - Blagosklonny, M V AU - Liewehr, D AU - Fojo, T AU - Bates, S E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1610 EP - 1617 VL - 7 IS - 6 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Coloring Agents KW - Cyclosporins KW - P-Glycoprotein KW - Taxoids KW - Tetrazolium Salts KW - Thiazoles KW - 6-hydroxytaxol KW - 153212-75-0 KW - thiazolyl blue KW - EUY85H477I KW - Paclitaxel KW - P88XT4IS4D KW - valspodar KW - Q7ZP55KF3X KW - Bilirubin KW - RFM9X3LJ49 KW - Index Medicus KW - Coloring Agents -- pharmacology KW - Dose-Response Relationship, Drug KW - HL-60 Cells KW - Humans KW - Microsomes, Liver -- metabolism KW - K562 Cells KW - Tetrazolium Salts -- pharmacology KW - Chromatography, High Pressure Liquid KW - Thiazoles -- pharmacology KW - Bilirubin -- metabolism KW - Models, Chemical KW - Inhibitory Concentration 50 KW - Time Factors KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Paclitaxel -- blood KW - Paclitaxel -- metabolism KW - Paclitaxel -- pharmacokinetics KW - Paclitaxel -- analogs & derivatives KW - Cyclosporins -- pharmacology KW - Antineoplastic Agents, Phytogenic -- metabolism KW - P-Glycoprotein -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70932628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=The+P-glycoprotein+antagonist+PSC+833+increases+the+plasma+concentrations+of+6alpha-hydroxypaclitaxel%2C+a+major+metabolite+of+paclitaxel.&rft.au=Kang%2C+M+H%3BFigg%2C+W+D%3BAndo%2C+Y%3BBlagosklonny%2C+M+V%3BLiewehr%2C+D%3BFojo%2C+T%3BBates%2C+S+E&rft.aulast=Kang&rft.aufirst=M&rft.date=2001-06-01&rft.volume=7&rft.issue=6&rft.spage=1610&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding. AN - 70930399; 11408162 AB - High affinity binding of peptides to Src homology 2 (SH2) domains, often requires the presence of phosphotyrosyl (pTyr) or pTyr-mimicking moieties in the N-terminal position of the binding ligand. Several reports have shown that N(alpha)-acylation of the critical pTyr residue can result in increased SH2 domain binding potency. For Grb2 SH2 domains which recognize pTyr-Xxx-Asn-NH(2) motifs, significant potency enhancement can be incurred by N(alpha)-(3-amino)Z derivatization of tripeptides such as pTyr-Ile-Asn-NH(2). Using ligands based on the high affinity pY-Ac(6)c-Asn-(naphthylpropylamide) motif, (where Ac(6)c=1-aminocyclohexanecarboxylic acid), additional reports have shown moderate potentiating effects of N(alpha)-oxalyl derivatization. The current study examined variations of the N(alpha)-oxalyl theme in the context of a Xxx-Ac(6)c-Asn-(naphthylpropylamide) platform, where Xxx=the hydrolytically stable pTyr mimetics phosphonomethyl phenylalanine (Pmp) or carboxymethyl phenylalanine (Cmf). The effects of N(alpha)-(3-amino)Z derivatization were also investigated for this platform, to ascertain whether the large binding enhancement reported for tripeptides such as pTyr-Ile-Asn-NH(2) could be observed. In ELISA-based extracellular Grb2 SH2 domain binding assays, it was found for the Pmp-based series, that extending the oxalyl carboxyl out by one methylene unit or replacing carboxyl functionality with a tetrazole isostere, resulted in binding potency greater than the parent N(alpha)-acetyl-containing compound, with enhancement approximating that observed for the N(alpha)-oxalyl derivative. When Cmf was used as the pTyr mimetic, only modest differences in IC(50) values were observed for the series. Examination of the N(alpha)-(3-amino)Z derivatized Pmp-Ac(6)c-Asn-(naphthylpropylamide), showed that binding affinity was reduced relative to the parent N(alpha)-acetyl analogue, in contrast to the reported significant enhancement of affinity observed with other peptide ligands. Treatment of MDA-453 tumor cells, which are mitogenically driven through erbB-2 tyrosine kinase-dependent pathways, with Pmp-containing inhibitors resulted in growth inhibition, with the N(alpha)-oxalyl and N(alpha)-malonyl-containing compounds exhibiting IC(50) values (4.3 and 4.6 microM, respectively) approximately five-fold lower than the parent N(alpha)-acetyl-containing compound. Tetrazole and N(alpha)-(3-amino)Z-containing inhibitors were from two- to four-fold less potent than these latter analogues in the growth inhibition assays. JF - Bioorganic & medicinal chemistry AU - Burke, T R AU - Yao, Z J AU - Gao, Y AU - Wu, J X AU - Zhu, X AU - Luo, J H AU - Guo, R AU - Yang, D AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 376, FCRDC, Frederick, MD 21702-1201, USA. tburke@helix.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1439 EP - 1445 VL - 9 IS - 6 SN - 0968-0896, 0968-0896 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Amides KW - Antineoplastic Agents KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Ligands KW - Naphthalenes KW - Oligopeptides KW - Proteins KW - Tetrazoles KW - 1H-tetrazole KW - 288-94-8 KW - Index Medicus KW - Tumor Cells, Cultured KW - Tetrazoles -- chemistry KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Inhibitory Concentration 50 KW - Drug Screening Assays, Antitumor -- methods KW - Amides -- chemistry KW - Structure-Activity Relationship KW - Binding Sites KW - Proteins -- drug effects KW - Naphthalenes -- pharmacology KW - Naphthalenes -- chemistry KW - Oligopeptides -- chemistry KW - Antineoplastic Agents -- metabolism KW - Oligopeptides -- metabolism KW - Oligopeptides -- pharmacology KW - Antineoplastic Agents -- chemistry KW - Proteins -- metabolism KW - Antineoplastic Agents -- pharmacology KW - src Homology Domains -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70930399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=N-terminal+carboxyl+and+tetrazole-containing+amides+as+adjuvants+to+Grb2+SH2+domain+ligand+binding.&rft.au=Burke%2C+T+R%3BYao%2C+Z+J%3BGao%2C+Y%3BWu%2C+J+X%3BZhu%2C+X%3BLuo%2C+J+H%3BGuo%2C+R%3BYang%2C+D&rft.aulast=Burke&rft.aufirst=T&rft.date=2001-06-01&rft.volume=9&rft.issue=6&rft.spage=1439&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry&rft.issn=09680896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early indicators of response in biologically based risk assessment for nongenotoxic carcinogens. AN - 70929694; 11407940 AB - The proposed existence of dose-response thresholds for nongenotoxic carcinogens has led to a major controversy in the risk extrapolation process. To resolve this debate, there has been a significant investment in mechanism-based risk assessment research. The ability to utilize this mechanistic research for risk assessment procedures is still limited and may not warrant the expense. Alternatively, an approach can be used to identify dose-response thresholds through the utilization of sensitive indicators of biological response. This approach does not rely upon a mechanistic framework for the development of pathology, is solely dependent on already existing technology, and takes into account the possibility of background levels of pathway activation. For this approach, sensitive biochemical responses need to be identified and linked to the introduction of the toxicant through dose response, by time of response, and, when possible, through a proposed biochemical mechanism. The weakness of this approach is that more sensitive unidentified responses may exist requiring that a safety factor of 10 be used to define a NOEL. For dioxin-like compounds, using a surrogate marker of response CYP1A1 induction, this approach yields an estimate of the acceptable daily intake of 5-50 fg/kg/day. This limit is remarkably similar to the results of the original EPA linear extrapolation (6 fg/kg/day). A similar approach can be used for other nongenotoxic carcinogens and the analysis can be completed within 1 year. JF - Regulatory toxicology and pharmacology : RTP AU - Gastel, J A AD - National Institutes of Health, Building 49, Room 5A-32, Bethesda, Maryland 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 393 EP - 398 VL - 33 IS - 3 SN - 0273-2300, 0273-2300 KW - Carcinogens KW - 0 KW - Dioxins KW - Environmental Pollutants KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Policy Making KW - Public Health KW - No-Observed-Adverse-Effect Level KW - Humans KW - Enzyme Induction KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Forecasting KW - Public Policy KW - Structure-Activity Relationship KW - Risk Assessment KW - Models, Theoretical KW - Cytochrome P-450 CYP1A1 -- drug effects KW - Dioxins -- adverse effects KW - Environmental Pollutants -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70929694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Early+indicators+of+response+in+biologically+based+risk+assessment+for+nongenotoxic+carcinogens.&rft.au=Gastel%2C+J+A&rft.aulast=Gastel&rft.aufirst=J&rft.date=2001-06-01&rft.volume=33&rft.issue=3&rft.spage=393&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis B, aflatoxin B(1), and p53 codon 249 mutation in hepatocellular carcinomas from Guangxi, People's Republic of China, and a meta-analysis of existing studies. AN - 70926952; 11401911 AB - The incidence of hepatocellular carcinomas (HCC) varies widely worldwide, with some of the highest incidence rates found in China. Chronic infection with the hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs are the main risk factors. A G to T transversion at codon 249 of the p53 gene (249(ser)) is commonly found in HCCs from patients in regions with dietary aflatoxin exposure. Because HBV infection is often endemic in high aflatoxin exposure areas, it is still unclear whether HBV acts as a confounder or as a synergistic partner in the development of the 249(ser) p53 mutation. Our report has two aims. First, we contribute data on HCCs from southern Guangxi, a high aflatoxin exposure area. Using DNA sequencing, we found that 36% (18 of 50) of tumors had a 249(ser) mutation. Also, 50% (30 of 60) were positive for p53 protein accumulation and 78% (28 of 36) were positive for HBV surface antigen, as detected by immunohistochemistry. Second, we present a meta-analysis, using our results along with those from 48 published studies, that examines the interrelationships among aflatoxin exposure, HBV infection, and p53 mutations in HCCs. We used a method that takes into account both within-study and study-to-study variability and found that the mean proportion of HCCs with the 249(ser) mutation was positively correlated with aflatoxin exposure (P = 0.0001). We found little evidence for an HBV-aflatoxin interaction modulating the presence of the p53 249(ser) mutation or any type of p53 mutation. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Stern, M C AU - Umbach, D M AU - Yu, M C AU - London, S J AU - Zhang, Z Q AU - Taylor, J A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 617 EP - 625 VL - 10 IS - 6 SN - 1055-9965, 1055-9965 KW - DNA, Neoplasm KW - 0 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Humans KW - DNA Mutational Analysis KW - China -- epidemiology KW - Point Mutation KW - Environmental Exposure KW - Incidence KW - Diet KW - Carcinoma, Hepatocellular -- virology KW - Liver Neoplasms -- pathology KW - Hepatitis B -- complications KW - Aflatoxin B1 -- adverse effects KW - Hepatitis B virus -- pathogenicity KW - Carcinoma, Hepatocellular -- genetics KW - Genes, p53 -- genetics KW - Liver Neoplasms -- virology KW - Carcinoma, Hepatocellular -- pathology KW - DNA, Neoplasm -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70926952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Hepatitis+B%2C+aflatoxin+B%281%29%2C+and+p53+codon+249+mutation+in+hepatocellular+carcinomas+from+Guangxi%2C+People%27s+Republic+of+China%2C+and+a+meta-analysis+of+existing+studies.&rft.au=Stern%2C+M+C%3BUmbach%2C+D+M%3BYu%2C+M+C%3BLondon%2C+S+J%3BZhang%2C+Z+Q%3BTaylor%2C+J+A&rft.aulast=Stern&rft.aufirst=M&rft.date=2001-06-01&rft.volume=10&rft.issue=6&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of T-cell responsiveness by inducible cAMP early repressor (ICER). AN - 70920531; 11404394 AB - Depending on the nature of the costimulation of T lymphocytes, expression of regulatory cytokines and chemokines is either susceptible or resistant to cyclic AMP (cAMP)-mediated inhibition. Our data show that cAMP-mediated inhibition of endogenously expressed cytokines, which is characteristic for T helper (Th) 1- and Th 2-like phenotypes, correlates with the induction of a potent transcriptional repressor, inducible cAMP early repressor (ICER), in both subsets of T cells activated under conditions of suboptimal interleukin-2 (IL-2) expression. Importantly, Th-specific expression of certain chemokines is also susceptible to cAMP-mediated transcriptional attenuation. To determine whether ICER per se, rather than forskolin-mediated elevation of intracellular cAMP, is responsible for the observed inhibitory effect, we generated transgenic mice expressing ICER under the control of a lymphocyte-specific lck promoter. On stimulation, transgenic thymocytes overexpressing ICER exhibited reduced levels of IL-2 and interferon (IFN)-gamma and failed to express the macrophage inflammatory protein (MIP)-1alpha and MIP-1beta genes. Splenic T cells from ICER-transgenic mice showed a defect in proliferation and lacked a mixed lymphocyte reaction response, implying that ICER-mediated inhibition of cytokine and chemokine expression might play an important role in T-cell inactivation. JF - Journal of leukocyte biology AU - Bodor, J AU - Feigenbaum, L AU - Bodorova, J AU - Bare, C AU - Reitz, M S AU - Gress, R E AD - Experimental Immunology Branch, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1053 EP - 1059 VL - 69 IS - 6 SN - 0741-5400, 0741-5400 KW - Chemokines KW - 0 KW - Cytokines KW - DNA-Binding Proteins KW - Interleukin-2 KW - Repressor Proteins KW - Cyclic AMP Response Element Modulator KW - 135844-64-3 KW - Colforsin KW - 1F7A44V6OU KW - Ionomycin KW - 56092-81-0 KW - Interferon-gamma KW - 82115-62-6 KW - Cyclic AMP KW - E0399OZS9N KW - Dinoprostone KW - K7Q1JQR04M KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Dinoprostone -- pharmacology KW - Transcription, Genetic -- drug effects KW - Humans KW - Ionomycin -- pharmacology KW - Interleukin-2 -- genetics KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Lymphocyte Activation -- drug effects KW - Colforsin -- pharmacology KW - Promoter Regions, Genetic KW - Second Messenger Systems -- physiology KW - Second Messenger Systems -- drug effects KW - Interferon-gamma -- genetics KW - Chemokines -- genetics KW - Spleen -- cytology KW - Lymphocyte Culture Test, Mixed KW - Cell Division -- drug effects KW - Interleukin-2 -- biosynthesis KW - Interferon-gamma -- biosynthesis KW - Chemokines -- biosynthesis KW - Mice KW - Mice, Inbred C57BL KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Th2 Cells -- metabolism KW - Cytokines -- genetics KW - Cytokines -- biosynthesis KW - Th1 Cells -- drug effects KW - Cyclic AMP -- pharmacology KW - Th2 Cells -- drug effects KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Th1 Cells -- metabolism KW - Gene Expression Regulation -- drug effects KW - DNA-Binding Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70920531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Suppression+of+T-cell+responsiveness+by+inducible+cAMP+early+repressor+%28ICER%29.&rft.au=Bodor%2C+J%3BFeigenbaum%2C+L%3BBodorova%2C+J%3BBare%2C+C%3BReitz%2C+M+S%3BGress%2C+R+E&rft.aulast=Bodor&rft.aufirst=J&rft.date=2001-06-01&rft.volume=69&rft.issue=6&rft.spage=1053&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - O(6)-allyl protected deoxyguanosine adducts of polycyclic aromatic hydrocarbons as building blocks for the synthesis of oligonucleotides. AN - 70920202; 11409942 AB - We describe a synthetic strategy for the preparation of oligonucleotides using N(2)-alkylated and O(6)-allyl protected deoxyguanosine phosphoramidite building blocks derived from cis- and trans-opened (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and from trans-opened (+/-)-3alpha,4beta-dihydroxy-1alpha,2alpha-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene. The appropriately blocked phosphoramidite building blocks were obtained as mixtures of the cis- and trans-opened diol epoxide adducts upon initial reaction of the diol epoxides with O(6)-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine. Key to the present approach is the removal of the O(6)-allyl protecting group utilizing a palladium catalyst prior to release of the constructed oligonucleotide with ammonia from the solid support. The methodology described enables a very convenient access to oligonucleotides containing cis- and trans-N(2)-deoxyguanosine adducts of polycyclic aromatic hydrocarbons in different sequence contexts. JF - Chemical research in toxicology AU - Kroth, H AU - Yagi, H AU - Sayer, J M AU - Kumar, S AU - Jerina, D M AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 708 EP - 719 VL - 14 IS - 6 SN - 0893-228X, 0893-228X KW - DNA Adducts KW - 0 KW - Environmental Pollutants KW - Oligonucleotides KW - Polycyclic Aromatic Hydrocarbons KW - Palladium KW - 5TWQ1V240M KW - Ammonia KW - 7664-41-7 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Palladium -- chemistry KW - Oligonucleotides -- chemical synthesis KW - Deoxyguanosine -- chemistry KW - Polycyclic Aromatic Hydrocarbons -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70920202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=O%286%29-allyl+protected+deoxyguanosine+adducts+of+polycyclic+aromatic+hydrocarbons+as+building+blocks+for+the+synthesis+of+oligonucleotides.&rft.au=Kroth%2C+H%3BYagi%2C+H%3BSayer%2C+J+M%3BKumar%2C+S%3BJerina%2C+D+M&rft.aulast=Kroth&rft.aufirst=H&rft.date=2001-06-01&rft.volume=14&rft.issue=6&rft.spage=708&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative carcinogenicity of 1,3-butadiene, isoprene, and chloroprene in rats and mice. AN - 70917873; 11397379 AB - 1,3-Butadiene, isoprene (2-methyl-1,3-butadiene), and chloroprene (2-chloro-1,3-butadiene) are high-production-volume chemicals used mainly in the manufacture of synthetic rubber. Inhalation studies have demonstrated multiple organ tumorigenic effects with each of these chemicals in mice and rats. Sites of tumor induction by these epoxide-forming chemicals were compared to each other and to ethylene oxide, a chemical classified by the National Toxicology Program (NTP) and by the International Agency for Research on Cancer (IARC) as carcinogenic to humans. For this group of chemicals, there are substantial species differences in sites of neoplasia; neoplasia of the mammary gland is the only common tumorigenic effect in rats and mice. Within each species, there are several common sites of tumor induction; these include the hematopoietic system, circulatory system, lung, liver, forestomach, Harderian gland, and mammary gland in mice, and the mammary gland and possibly the brain, thyroid, testis, and kidney in rats. For studies in which individual animal data were available, mortality-adjusted tumor rates were calculated, and estimates were made of the shape of the exposure-response curves and ED10 values (i.e. exposure concentrations associated with an excess risk of 10% at each tumor site). Most tumorigenic effects reported here were consistent with linear or supralinear models. For chloroprene and butadiene, the most potent response was for the induction of lung neoplasms in female mice, with ED10 values of 0.3 ppm. Based on animal cancer data, isoprene and chloroprene are listed in the NTP's Report on Carcinogens (RoC) as reasonably anticipated to be a human carcinogen. Butadiene is listed in the RoC as known to be a human carcinogen 'based on sufficient evidence of carcinogenicity from studies in humans, including epidemiological and mechanistic information', with support from experimental studies in laboratory animals. Epidemiology data for isoprene and chloroprene are not considered adequate to evaluate the potential carcinogenicity of these agents in humans. JF - Chemico-biological interactions AU - Melnick, R L AU - Sills, R C AD - National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA. melnickr@niehs.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 27 EP - 42 VL - 135-136 SN - 0009-2797, 0009-2797 KW - Air Pollutants, Occupational KW - 0 KW - Butadienes KW - Carcinogens KW - Hemiterpenes KW - Pentanes KW - isoprene KW - 0A62964IBU KW - Chloroprene KW - 126-99-8 KW - Rubber KW - 9006-04-6 KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Occupational Exposure KW - Mammary Neoplasms, Experimental -- chemically induced KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Risk Factors KW - Humans KW - Mice KW - Air Pollutants, Occupational -- toxicity KW - Administration, Inhalation KW - Male KW - Female KW - Butadienes -- toxicity KW - Carcinogens -- toxicity KW - Chloroprene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70917873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Comparative+carcinogenicity+of+1%2C3-butadiene%2C+isoprene%2C+and+chloroprene+in+rats+and+mice.&rft.au=Melnick%2C+R+L%3BSills%2C+R+C&rft.aulast=Melnick&rft.aufirst=R&rft.date=2001-06-01&rft.volume=135-136&rft.issue=&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current research on respiratory viral infections: Third International Symposium. AN - 70912938; 11397506 JF - Antiviral research AU - Schmidt, A C AU - Couch, R B AU - Galasso, G J AU - Hayden, F G AU - Mills, J AU - Murphy, B R AU - Chanock, R M AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 7 Center Drive, Bethesda, MD 20892-0720, USA. aschmidt@niaid.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 157 EP - 196 VL - 50 IS - 3 SN - 0166-3542, 0166-3542 KW - Antiviral Agents KW - 0 KW - Vaccines KW - Index Medicus KW - Vaccines -- adverse effects KW - Vaccines -- immunology KW - Adenoviridae -- immunology KW - Animals KW - Humans KW - Vaccines -- therapeutic use KW - Disease Outbreaks KW - Adenoviridae -- genetics KW - Orthomyxoviridae -- immunology KW - Respiratory Syncytial Viruses -- immunology KW - Respiratory Syncytial Viruses -- pathogenicity KW - Rhinovirus -- pathogenicity KW - Adenoviridae -- pathogenicity KW - Respiratory Syncytial Viruses -- genetics KW - Risk Factors KW - Rhinovirus -- genetics KW - Orthomyxoviridae -- genetics KW - Orthomyxoviridae -- pathogenicity KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- administration & dosage KW - Respiratory Tract Infections -- epidemiology KW - Respiratory Tract Infections -- virology KW - Antiviral Agents -- adverse effects KW - Respiratory Tract Infections -- drug therapy KW - Respiratory Tract Infections -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70912938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=Current+research+on+respiratory+viral+infections%3A+Third+International+Symposium.&rft.au=Schmidt%2C+A+C%3BCouch%2C+R+B%3BGalasso%2C+G+J%3BHayden%2C+F+G%3BMills%2C+J%3BMurphy%2C+B+R%3BChanock%2C+R+M&rft.aulast=Schmidt&rft.aufirst=A&rft.date=2001-06-01&rft.volume=50&rft.issue=3&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiological modeling of butadiene disposition in mice and rats. AN - 70908683; 11397397 AB - The earliest physiological models of 1,3-butadiene disposition reproduced uptake of the gas from closed chambers but over-predicted steady-state circulating concentrations of the mutagenic intermediates 1,2-epoxybut-3-ene and 1,2:3,4-diepoxybutane. A preliminary model based on the observation of a transient complex between cytochrome P450 and microsomal epoxide hydrolase on the endoplasmic reticulum membrane reproduced the blood epoxide concentrations as well as the chamber uptake data. This model was enhanced by the addition of equations for the production and detoxication of 3,4-epoxybutane-1,2-diol in the liver, lungs, and kidneys. The model includes flow-restricted delivery of butadiene and its metabolites to compartments for lungs, liver, fat, kidneys, gastrointestinal tract, other rapidly perfused tissues, and other slowly perfused tissues. Blood was distributed among compartments for arterial, venous, and tissue capillary spaces. Channeling of the three bound epoxides to epoxide hydrolase and their release from the endoplasmic reticulum are competing processes in this model. Parameters were estimated to fit data for chamber uptake of butadiene and epoxybutene, steady-state blood concentrations of epoxybutene and diepoxybutane, and the fractions of the inhaled dose of butadiene that appears as various excreted metabolites. The optimal values of the apparent K(m)s of membrane-bound epoxides for epoxide hydrolase were only 5% of the values for the cytosolic substrate, consistent with the observation of a transient complex between epoxide hydrolase and the cytochrome P450 that produces the epoxide. This proximity effect corresponds to the notion that epoxides produced in situ have privileged access to epoxide hydrolase. The model also predicts considerable accumulation of epoxybutanediol, in agreement with the observation that most of the DNA adducts in animals exposed to butadiene arise from this metabolite. JF - Chemico-biological interactions AU - Kohn, M C AU - Melnick, R L AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Mail Drop A3-06, Research Triangle Park, NC 27709, USA. kohn@valiant.niehs.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 285 EP - 301 VL - 135-136 SN - 0009-2797, 0009-2797 KW - Butadienes KW - 0 KW - DNA Adducts KW - Epoxy Compounds KW - 3,4-epoxy-1-butene KW - 478ERR5NKR KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Epoxide Hydrolases -- metabolism KW - Animals KW - Kinetics KW - Epoxy Compounds -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Tissue Distribution KW - Models, Biological KW - Male KW - DNA Adducts -- metabolism KW - Butadienes -- chemistry KW - Butadienes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70908683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Physiological+modeling+of+butadiene+disposition+in+mice+and+rats.&rft.au=Kohn%2C+M+C%3BMelnick%2C+R+L&rft.aulast=Kohn&rft.aufirst=M&rft.date=2001-06-01&rft.volume=135-136&rft.issue=&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Markers for carcinogenicity among butadiene-polymer workers in China. AN - 70906183; 11397406 AB - We examined a spectrum of genotoxic and other outcomes in 41 butadiene-polymer production workers and 38 nonexposed controls, in China, to explore the role of butadiene in human carcinogenesis. Among butadiene-exposed workers, median air exposure was 2 ppm (6-h TWA), due largely to intermittent high-level exposures. Compared to unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P<0.0001), and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P=0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A, or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P=0.002) and platelet counts (P=0.07) and lymphocytes as a percent of white blood cells were moderately correlated with greater THBVal levels (Spearman's rho=0.32, P=0.07). Among butadiene-exposed workers, several serum cytokines correlated with THBVal adduct levels. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure. JF - Chemico-biological interactions AU - Hayes, R B AU - Zhang, L AU - Swenberg, J A AU - Yin, S N AU - Xi, L AU - Wiencke, J AU - Bechtold, W E AU - Yao, M AU - Rothman, N AU - Haas, R AU - O'Neill, J P AU - Wiemels, J AU - Dosemeci, M AU - Li, G AU - Smith, M T AD - Occupational Epidemology Branch, National Cancer Institute, National Institutes of Health, EPS 8114, Bethesda, MD, USA. hayes@mail.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 455 EP - 464 VL - 135-136 SN - 0009-2797, 0009-2797 KW - Air Pollutants, Occupational KW - 0 KW - Biomarkers KW - Butadienes KW - Carcinogens KW - Hemoglobins KW - Polymers KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Hemoglobins -- drug effects KW - Occupational Exposure KW - Humans KW - Air Pollutants, Occupational -- toxicity KW - Polymers -- toxicity KW - Mutagenicity Tests KW - Air Pollutants, Occupational -- analysis KW - Biomarkers -- analysis KW - Sister Chromatid Exchange -- drug effects KW - Hemoglobins -- chemistry KW - China KW - Female KW - Male KW - Butadienes -- toxicity KW - Butadienes -- analysis KW - Carcinogens -- toxicity KW - Carcinogens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70906183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Markers+for+carcinogenicity+among+butadiene-polymer+workers+in+China.&rft.au=Hayes%2C+R+B%3BZhang%2C+L%3BSwenberg%2C+J+A%3BYin%2C+S+N%3BXi%2C+L%3BWiencke%2C+J%3BBechtold%2C+W+E%3BYao%2C+M%3BRothman%2C+N%3BHaas%2C+R%3BO%27Neill%2C+J+P%3BWiemels%2C+J%3BDosemeci%2C+M%3BLi%2C+G%3BSmith%2C+M+T&rft.aulast=Hayes&rft.aufirst=R&rft.date=2001-06-01&rft.volume=135-136&rft.issue=&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Point mutations of K-ras and H-ras genes in forestomach neoplasms from control B6C3F1 mice and following exposure to 1,3-butadiene, isoprene or chloroprene for up to 2-years. AN - 70906131; 11397402 AB - 1,3 Butadiene (BD), isoprene (IP) and chloroprene (CP) are structural analogs. There were significantly increased incidences of forestomach neoplasms in B6C3F1 mice exposed to BD, IP or CP by inhalation for up to 2-years. The present study was designed to characterize genetic alterations in K- and H-ras proto-oncogenes in a total of 52 spontaneous and chemically induced forestomach neoplasms. ras mutations were identified by restriction fragment length polymorphism, single strand conformational polymorphism analysis, and cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded forestomach neoplasms. A higher frequency of K- and H-ras mutations was identified in BD-, IP- and CP-induced forestomach neoplasms (83, 70 and 57%, respectively, or combined 31/41, 76%) when compared to spontaneous forestomach neoplasms (4/11, 36%). Also a high frequency of H-ras codon 61 CAA-->CTA transversions (10/41, 24%) was detected in chemically induced forestomach neoplasms, but none were present in the spontaneous forestomach neoplasms examined. Furthermore, an increased frequency (treated 13/41, 32% versus untreated 1/11, 9%) of GGC-->CGC transversion at K-ras codon 13 was seen in BD-, and IP-induced forestomach neoplasms, similar to the predominant K-ras mutation pattern observed in BD-induced mouse lung neoplasms. These data suggest that the epoxide intermediates of the structurally related chemicals (BD, IP, and CP) may cause DNA damage in K-ras and H-ras proto-oncogenes of B6C3F1 mice following inhalation exposure and that mutational activation of these genes may be critical events in the pathogenesis of forestomach neoplasms induced in the B6C3F1 mouse. JF - Chemico-biological interactions AU - Sills, R C AU - Hong, H L AU - Boorman, G A AU - Devereux, T R AU - Melnick, R L AD - Laboratory of Experimental Pathology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. sills@niehs.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 373 EP - 386 VL - 135-136 SN - 0009-2797, 0009-2797 KW - Butadienes KW - 0 KW - DNA Primers KW - Hemiterpenes KW - Pentanes KW - isoprene KW - 0A62964IBU KW - Chloroprene KW - 126-99-8 KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Animals KW - Base Sequence KW - Polymorphism, Restriction Fragment Length KW - DNA Primers -- genetics KW - DNA Damage KW - Humans KW - Mice KW - Time Factors KW - Polymorphism, Single-Stranded Conformational KW - Male KW - Female KW - Stomach Neoplasms -- pathology KW - Stomach Neoplasms -- chemically induced KW - Genes, ras -- drug effects KW - Butadienes -- toxicity KW - Stomach Neoplasms -- genetics KW - Point Mutation KW - Chloroprene -- toxicity KW - Butadienes -- administration & dosage KW - Chloroprene -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70906131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Point+mutations+of+K-ras+and+H-ras+genes+in+forestomach+neoplasms+from+control+B6C3F1+mice+and+following+exposure+to+1%2C3-butadiene%2C+isoprene+or+chloroprene+for+up+to+2-years.&rft.au=Sills%2C+R+C%3BHong%2C+H+L%3BBoorman%2C+G+A%3BDevereux%2C+T+R%3BMelnick%2C+R+L&rft.aulast=Sills&rft.aufirst=R&rft.date=2001-06-01&rft.volume=135-136&rft.issue=&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uterine adenocarcinoma in mice treated neonatally with genistein. AN - 70904909; 11389053 AB - The developing fetus is uniquely sensitive to perturbation with estrogenic chemicals. The carcinogenic effect of prenatal exposure to diethylstilbestrol (DES) is the classic example. Because phytoestrogen use in nutritional and pharmaceutical applications for infants and children is increasing, we investigated the carcinogenic potential of genistein, a naturally occurring plant estrogen in soy, in an experimental animal model previously reported to result in a high incidence of uterine adenocarcinoma after neonatal DES exposure. Outbred female CD-1 mice were treated on days 1-5 with equivalent estrogenic doses of DES (0.001 mg/kg/day) or genistein (50 mg/kg/day). At 18 months, the incidence of uterine adenocarcinoma was 35% for genistein and 31% for DES. These data suggest that genistein is carcinogenic if exposure occurs during critical periods of differentiation. Thus, the use of soy-based infant formulas in the absence of medical necessity and the marketing of soy products designed to appeal to children should be closely examined. JF - Cancer research AU - Newbold, R R AU - Banks, E P AU - Bullock, B AU - Jefferson, W N AD - Developmental Endocrinology Section, Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. newbold1@niehs.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 4325 EP - 4328 VL - 61 IS - 11 SN - 0008-5472, 0008-5472 KW - Estrogens, Non-Steroidal KW - 0 KW - Isoflavones KW - Phytoestrogens KW - Plant Preparations KW - Diethylstilbestrol KW - 731DCA35BT KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Animals KW - Fallopian Tubes -- drug effects KW - Diethylstilbestrol -- toxicity KW - Mice KW - Fallopian Tubes -- abnormalities KW - Uterus -- drug effects KW - Pregnancy KW - Estrogens, Non-Steroidal -- toxicity KW - Uterus -- abnormalities KW - Female KW - Male KW - Adenocarcinoma -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Genistein -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70904909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Uterine+adenocarcinoma+in+mice+treated+neonatally+with+genistein.&rft.au=Newbold%2C+R+R%3BBanks%2C+E+P%3BBullock%2C+B%3BJefferson%2C+W+N&rft.aulast=Newbold&rft.aufirst=R&rft.date=2001-06-01&rft.volume=61&rft.issue=11&rft.spage=4325&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral and neural consequences of prenatal exposure to nicotine. AN - 70902712; 11392340 AB - To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns. This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined. A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine. Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Ernst, M AU - Moolchan, E T AU - Robinson, M L AD - Brain Imaging Center in the Neuroimaging Branch of the Intramural Research Program of the National Institute on Drug Abuse, Bethesda, MD 20892-0135, USA. ernstm@intra.nimh.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 630 EP - 641 VL - 40 IS - 6 SN - 0890-8567, 0890-8567 KW - Receptors, Nicotinic KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Rats KW - Maternal Behavior KW - Infant KW - Animals KW - Time KW - Dose-Response Relationship, Drug KW - Humans KW - Female KW - Pregnancy KW - Child, Preschool KW - Fetal Diseases -- etiology KW - Cognition Disorders -- etiology KW - Attention Deficit Disorder with Hyperactivity -- epidemiology KW - Cognition Disorders -- epidemiology KW - Brain -- drug effects KW - Nicotine -- adverse effects KW - Smoking -- adverse effects KW - Receptors, Nicotinic -- drug effects KW - Attention Deficit and Disruptive Behavior Disorders -- epidemiology KW - Attention Deficit and Disruptive Behavior Disorders -- etiology KW - Attention Deficit Disorder with Hyperactivity -- etiology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70902712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Behavioral+and+neural+consequences+of+prenatal+exposure+to+nicotine.&rft.au=Ernst%2C+M%3BMoolchan%2C+E+T%3BRobinson%2C+M+L&rft.aulast=Ernst&rft.aufirst=M&rft.date=2001-06-01&rft.volume=40&rft.issue=6&rft.spage=630&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MAPS: a microarray project system for gene expression experiment information and data validation. AN - 70898769; 11395436 AB - MAPS is a MicroArray Project System for management and interpretation of microarray gene expression experiment information and data. Microarray project information is organized to track experiments and results that are: (1) validated by performing analysis on stored replicate gene expression data; and (2) queried according to the biological classifications of genes deposited on microarray chips. JF - Bioinformatics (Oxford, England) AU - Bushel, P R AU - Hamadeh, H AU - Bennett, L AU - Sieber, S AU - Martin, K AU - Nuwaysir, E F AU - Johnson, K AU - Reynolds, K AU - Paules, R S AU - Afshari, C A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA. bushel@niehs.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 564 EP - 565 VL - 17 IS - 6 SN - 1367-4803, 1367-4803 KW - Index Medicus KW - Programming Languages KW - Computer Communication Networks KW - Data Display KW - Oligonucleotide Array Sequence Analysis -- standards KW - Database Management Systems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70898769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics+%28Oxford%2C+England%29&rft.atitle=MAPS%3A+a+microarray+project+system+for+gene+expression+experiment+information+and+data+validation.&rft.au=Bushel%2C+P+R%3BHamadeh%2C+H%3BBennett%2C+L%3BSieber%2C+S%3BMartin%2C+K%3BNuwaysir%2C+E+F%3BJohnson%2C+K%3BReynolds%2C+K%3BPaules%2C+R+S%3BAfshari%2C+C+A&rft.aulast=Bushel&rft.aufirst=P&rft.date=2001-06-01&rft.volume=17&rft.issue=6&rft.spage=564&rft.isbn=&rft.btitle=&rft.title=Bioinformatics+%28Oxford%2C+England%29&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploiting cancer cell cycling for selective protection of normal cells. AN - 70893591; 11389048 AB - Chemotherapy of cancer is limited by its toxicity to normal cells. On the basis of discoveries in signal transduction and cell cycle regulation, novel mechanism-based therapeutics are being developed. Although these cell cycle modulators were designed to target cancer cells, some of them can also be applied for a different purpose, i.e., to protect normal cells against the lethality of chemotherapy. Loss of sensitivity of cancer cells to cell cycle inhibitors can be exploited for selective protection of normal cells that retain this response. Indeed, inhibition of redundant or overactivated pathways (e.g., growth factor-activated pathways) or stimulation of absent pathways in cancer cells (e.g., p53, Rb, and p16) may not arrest cycling of cancer cells. But growth arrest of normal cells will then permit selective killing of cancer cells by cycle-dependent chemotherapy. JF - Cancer research AU - Blagosklonny, M V AU - Pardee, A B AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. mikhailb@box-m.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 4301 EP - 4305 VL - 61 IS - 11 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Cell Cycle -- physiology KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle -- drug effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70893591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Exploiting+cancer+cell+cycling+for+selective+protection+of+normal+cells.&rft.au=Blagosklonny%2C+M+V%3BPardee%2C+A+B&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2001-06-01&rft.volume=61&rft.issue=11&rft.spage=4301&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the nicotine content of tobacco used in bidis and conventional cigarettes. AN - 70892727; 11387541 AB - To compare the nicotine content of 12 unfiltered brands of bidi cigarettes (hand rolled cigarettes imported from India) with 8 popular brands of filtered and unfiltered US and conventional cigarettes from India. Identical laboratory procedures were used to determine nicotine content (in duplicate) and physical characteristics. The nicotine concentration in the tobacco of bidi cigarettes (21.2 mg/g) was significantly greater than the tobacco from the commercial filtered (16.3 mg/g) and unfiltered cigarettes (13.5 mg/g). Bidi cigarettes contain higher concentrations of nicotine than conventional cigarettes. Therefore, it is logical to presume that bidi smokers are at risk of becoming nicotine dependent. These findings belief a popular belief among US teens that bidis are a safe alternative to commercial cigarettes. JF - Tobacco control AU - Malson, J L AU - Sims, K AU - Murty, R AU - Pickworth, W B AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 181 EP - 183 VL - 10 IS - 2 SN - 0964-4563, 0964-4563 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - United States KW - Chromatography, Gas KW - Humans KW - Adolescent KW - India KW - Plants, Toxic KW - Tobacco -- chemistry KW - Nicotine -- analysis KW - Tobacco Use Disorder -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70892727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=Comparison+of+the+nicotine+content+of+tobacco+used+in+bidis+and+conventional+cigarettes.&rft.au=Malson%2C+J+L%3BSims%2C+K%3BMurty%2C+R%3BPickworth%2C+W+B&rft.aulast=Malson&rft.aufirst=J&rft.date=2001-06-01&rft.volume=10&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=09644563&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of hydrophobic residues in the C1b domain of protein kinase C delta on ligand and phospholipid interactions. AN - 70891063; 11278612 AB - The C1 domains of conventional and novel protein kinase C (PKC) isoforms bind diacylglycerol and phorbol esters with high affinity. Highly conserved hydrophobic residues at or near the rim of the binding cleft in the second cysteine-rich domain of PKC-delta (PKC-deltaC1b) were mutated to probe their roles in ligand recognition and lipid interaction. [(3)H]Phorbol 12,13-dibutyrate (PDBu) binding was carried out both in the presence and absence of phospholipids to determine the contribution of lipid association to the ligand affinity. Lipid dependence was determined as a function of lipid concentration and composition. The binding properties of a high affinity branched diacylglycerol with lipophilicity similar to PDBu were compared with those of PDBu to identify residues important for ligand selectivity. As expected, Leu-20 and Leu-24 strongly influenced binding. Substitution of either by aspartic acid abolished binding in either the presence or absence of phosphatidylserine. Mutation of Leu-20 to Arg or of Leu-24 to Lys caused a dramatic (340- and 250-fold, respectively) reduction in PDBu binding in the presence of lipid but only a modest reduction in the weaker binding of PDBu observed in the absence of lipid, suggesting that the main effect was on C1 domain -phospholipid interactions. Mutation of Leu-20 to Lys or of Trp-22 to Lys had modest (3-fold) effects and mutation of Phe-13 to Tyr or Lys was without effect. Binding of the branched diacylglycerol was less dependent on phospholipid and was more sensitive to mutation of Trp-22 to Tyr or Lys, especially in the presence of phospholipid, than was PDBu. In terms of specific PKC isoforms, our results suggest that the presence of Arg-20 in PKC-zeta may contribute to its lack of phorbol ester binding activity. More generally, the results emphasize the interplay between the C1 domain, ligand, and phospholipid in the ternary binding complex. JF - The Journal of biological chemistry AU - Wang, Q J AU - Fang, T W AU - Nacro, K AU - Marquez, V E AU - Wang, S AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion and Laboratory of Medicinal Chemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 19580 EP - 19587 VL - 276 IS - 22 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Ligands KW - Phorbol Esters KW - Phospholipids KW - Protein Isoforms KW - Recombinant Fusion Proteins KW - Tyrosine KW - 42HK56048U KW - Arginine KW - 94ZLA3W45F KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Leucine KW - GMW67QNF9C KW - Lysine KW - K3Z4F929H6 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Phorbol Esters -- metabolism KW - Lysine -- chemistry KW - Arginine -- chemistry KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - Glutathione Transferase -- metabolism KW - Amino Acid Sequence KW - Escherichia coli -- enzymology KW - Leucine -- chemistry KW - Protein Binding KW - Tyrosine -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Cysteine -- chemistry KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Mutation KW - Lipid Metabolism KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Phospholipids -- metabolism KW - Protein Kinase C -- chemistry KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70891063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Role+of+hydrophobic+residues+in+the+C1b+domain+of+protein+kinase+C+delta+on+ligand+and+phospholipid+interactions.&rft.au=Wang%2C+Q+J%3BFang%2C+T+W%3BNacro%2C+K%3BMarquez%2C+V+E%3BWang%2C+S%3BBlumberg%2C+P+M&rft.aulast=Wang&rft.aufirst=Q&rft.date=2001-06-01&rft.volume=276&rft.issue=22&rft.spage=19580&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-05-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of SCF/G-CSF prestimulation on radiation sensitivity and engraftment in nonmyeloablated murine hosts. AN - 70890896; 11378274 AB - Previous studies have shown improved engraftment in a murine model when granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) were administered for 5 days prior to irradiation, with significant levels of engraftment in the growth factor-preconditioned group even at very low radiation doses. We sought to explore the mechanisms behind this effect. The radiation sensitivity of mice with or without 5 days of prestimulation with G-CSF (200 microg/kg/d) and SCF (50 microg/kg/d) was compared. To further evaluate whether growth factor prestimulation enhances engraftment by mobilization of hematopoietic progenitors into peripheral blood, thus creating less endogenous competition within the marrow compartment, female mice were pretreated with 5 days of G-CSF/SCF or control diluent. Engraftment of 40 x 10(6) peripheral blood stem cells (PBSCs) harvested from G-CSF/SCF-mobilized male mice was compared in the two recipient groups. There was no difference in survival between the pretreated and control mice at the radiation doses tested. Additionally, there was no significant difference in the recovery of blood counts, bone marrow cellularity, colony-forming unit (CFU) content, or stem cell numbers assessed 4 months later in a competitive repopulation model. Engraftment levels of male cells did not differ between G-CSF/SCF-pretreated and control recipients, and could be detected in 30% of recipients at 20-24 weeks (4/12 in each group) at overall levels of 0.1-1%. The enhanced engraftment in cytokine pretreated recipients is unlikely to be due to increased endogenous stem-cell killing or to the creation of endogenous marrow "space" by egress of endogenous stem cells after cytokine prestimulation. JF - Experimental hematology AU - Giri, N AU - Kaushiva, A AU - Wu, T AU - Sellers, S E AU - Tisdale, J F AD - Molecular and Clinical Hematology Branch, NIDDK, Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 779 EP - 785 VL - 29 IS - 6 SN - 0301-472X, 0301-472X KW - Recombinant Proteins KW - 0 KW - Stem Cell Factor KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Hematopoietic Stem Cell Mobilization KW - Mice KW - Dose-Response Relationship, Radiation KW - Mice, Inbred BALB C KW - Leukocyte Count KW - Rats KW - Mice, Inbred Strains KW - Whole-Body Irradiation KW - Mice, Inbred C57BL KW - Female KW - Male KW - Bone Marrow Cells -- drug effects KW - Stem Cell Factor -- pharmacology KW - Hematopoietic Stem Cells -- cytology KW - Bone Marrow Cells -- radiation effects KW - Bone Marrow Cells -- cytology KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Hematopoietic Stem Cells -- radiation effects KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70890896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+hematology&rft.atitle=The+effects+of+SCF%2FG-CSF+prestimulation+on+radiation+sensitivity+and+engraftment+in+nonmyeloablated+murine+hosts.&rft.au=Giri%2C+N%3BKaushiva%2C+A%3BWu%2C+T%3BSellers%2C+S+E%3BTisdale%2C+J+F&rft.aulast=Giri&rft.aufirst=N&rft.date=2001-06-01&rft.volume=29&rft.issue=6&rft.spage=779&rft.isbn=&rft.btitle=&rft.title=Experimental+hematology&rft.issn=0301472X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of a human chloride channel. a paradigm for integrating input from calcium, type ii calmodulin-dependent protein kinase, and inositol 3,4,5,6-tetrakisphosphate. AN - 70890004; 11279175 AB - We have studied the regulation of Ca(2+)-dependent chloride (Cl(Ca)) channels in a human pancreatoma epithelial cell line (CFPAC-1), which does not express functional cAMP-dependent cystic fibrosis transmembrane conductance regulator chloride channels. In cell-free patches from these cells, physiological Ca(2+) concentrations activated a single class of 1-picosiemens Cl(-)-selective channels. The same channels were also stimulated by a purified type II calmodulin-dependent protein kinase (CaMKII), and in cell-attached patches by purinergic agonists. In whole-cell recordings, both Ca(2+)- and CaMKII-dependent mechanisms contributed to chloride channel stimulation by Ca(2+), but the CaMKII-dependent pathway was selectively inhibited by inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P(4)). This inhibitory effect of Ins(3,4,5,6)P(4) on Cl(Ca) channel stimulation by CaMKII was reduced by raising [Ca(2+)] and prevented by inhibition of protein phosphatase activity with 100 nm okadaic acid. These data provide a new context for understanding the physiological relevance of Ins(3,4,5,6)P(4) in the longer term regulation of Ca(2+)-dependent Cl(-) fluxes in epithelial cells. JF - The Journal of biological chemistry AU - Ho, M W AU - Kaetzel, M A AU - Armstrong, D L AU - Shears, S B AD - Inositide Signaling and Membrane Signaling Groups, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. ho1@niehs.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 18673 EP - 18680 VL - 276 IS - 22 SN - 0021-9258, 0021-9258 KW - Chloride Channels KW - 0 KW - Inositol Phosphates KW - Ionophores KW - Protein Isoforms KW - inositol-3,4,5,6-tetrakisphosphate KW - 112791-61-4 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Cyclic AMP KW - E0399OZS9N KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Calcium KW - SY7Q814VUP KW - Uridine Triphosphate KW - UT0S826Z60 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Electrophysiology KW - Models, Biological KW - Uridine Triphosphate -- metabolism KW - Epithelial Cells -- metabolism KW - Patch-Clamp Techniques KW - Tumor Cells, Cultured KW - Ionophores -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Cyclic AMP -- metabolism KW - Okadaic Acid -- pharmacology KW - Up-Regulation KW - Cell Membrane -- metabolism KW - Calcium -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Inositol Phosphates -- metabolism KW - Chloride Channels -- metabolism KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70890004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+a+human+chloride+channel.+a+paradigm+for+integrating+input+from+calcium%2C+type+ii+calmodulin-dependent+protein+kinase%2C+and+inositol+3%2C4%2C5%2C6-tetrakisphosphate.&rft.au=Ho%2C+M+W%3BKaetzel%2C+M+A%3BArmstrong%2C+D+L%3BShears%2C+S+B&rft.aulast=Ho&rft.aufirst=M&rft.date=2001-06-01&rft.volume=276&rft.issue=22&rft.spage=18673&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-05-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered nucleotide misinsertion fidelity associated with poliota-dependent replication at the end of a DNA template. AN - 70889134; 11387224 AB - A hallmark of human DNA polymerase iota (poliota) is the asymmetric fidelity of replication at template A and T when the enzyme extends primers annealed to a single-stranded template. Here, we report on the efficiency and accuracy of poliota-dependent replication at a nick, a gap, the very end of a template and from a mispaired primer. Poliota cannot initiate synthesis on a nicked DNA substrate, but fills short gaps efficiently. Surprisingly, poliota's ability to blunt-end a 1 bp recessed terminus is dependent upon the template nucleotide encountered and is highly erroneous. At template G, both C and T are inserted with roughly equal efficiency, whilst at template C, C and A are misinserted 8- and 3-fold more often than the correct base, G. Using substrates containing mispaired primer termini, we show that poliota can extend all 12 mispairs, but with differing efficiencies. Poliota can also extend a tandem mispair, especially when it is located within a short gap. The enzymatic properties of poliota appear consistent with that of a somatic hypermutase and suggest that poliota may be one of the low-fidelity DNA polymerases hypothesized to participate in the hypermutation of immunoglobulin variable genes in vivo. JF - The EMBO journal AU - Frank, E G AU - Tissier, A AU - McDonald, J P AU - Rapić-Otrin, V AU - Zeng, X AU - Gearhart, P J AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 2914 EP - 2922 VL - 20 IS - 11 SN - 0261-4189, 0261-4189 KW - DNA Primers KW - 0 KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Spleen -- immunology KW - Templates, Genetic KW - Substrate Specificity KW - B-Lymphocytes -- enzymology KW - Spleen -- enzymology KW - Base Pair Mismatch KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70889134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Altered+nucleotide+misinsertion+fidelity+associated+with+poliota-dependent+replication+at+the+end+of+a+DNA+template.&rft.au=Frank%2C+E+G%3BTissier%2C+A%3BMcDonald%2C+J+P%3BRapi%C4%87-Otrin%2C+V%3BZeng%2C+X%3BGearhart%2C+P+J%3BWoodgate%2C+R&rft.aulast=Frank&rft.aufirst=E&rft.date=2001-06-01&rft.volume=20&rft.issue=11&rft.spage=2914&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1166-71 [10655502] Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11922-7 [10518552] EMBO J. 2000 Jun 15;19(12):3100-9 [10856253] Mol Immunol. 2000 Feb-Mar;37(3-4):125-31 [10865111] Genes Dev. 2000 Jul 1;14(13):1642-50 [10887158] Mol Cell. 2000 Jun;5(6):1059-65 [10912000] Nature. 2000 Aug 31;406(6799):1015-9 [10984059] Annu Rev Biochem. 2000;69:497-529 [10966467] Mol Cell Biol. 2000 Oct;20(19):7099-108 [10982826] EMBO J. 2000 Oct 2;19(19):5259-66 [11013228] J Exp Med. 2000 Nov 20;192(10):F27-30 [11085756] Nature. 2000 Nov 9;408(6809):216-21 [11089977] Immunity. 2000 Nov;13(5):589-97 [11114372] Philos Trans R Soc Lond B Biol Sci. 2001 Jan 29;356(1405):53-60 [11205331] Nucleic Acids Res. 2001 Feb 15;29(4):928-35 [11160925] Nat Rev Mol Cell Biol. 2000 Nov;1(2):101-9 [11253362] Science. 2001 Mar 16;291(5511):2156-9 [11251121] J Biol Chem. 2001 May 4;276(18):15155-63 [11297519] J Clin Immunol. 2001 Mar;21(2):102-15 [11332649] Nature. 1966 Jul 16;211(5046):242-3 [5965537] Proc Natl Acad Sci U S A. 1983 Jun;80(11):3439-43 [6222379] J Biol Chem. 1987 Oct 25;262(30):14689-96 [3667598] EMBO J. 1988 Mar;7(3):727-38 [3396540] J Exp Med. 1990 Dec 1;172(6):1717-27 [2258702] Nucleic Acids Res. 1991 Aug 11;19(15):4045-57 [1870963] Nature. 1991 Dec 5;354(6352):389-92 [1956400] Biochim Biophys Acta. 1992 Nov 15;1171(1):11-8 [1420357] Nucleic Acids Res. 1993 Feb 25;21(4):787-802 [8451181] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2385-8 [8460148] Mol Cell Biol. 1993 Jul;13(7):4276-83 [8321229] J Exp Med. 1993 Oct 1;178(4):1293-307 [8376935] Cell. 1994 Apr 22;77(2):239-48 [8168132] Science. 1994 Jul 1;265(5168):103-6 [8016642] Methods Enzymol. 1995;262:232-56 [8594351] Trends Biochem Sci. 2000 Mar;25(3):143-7 [10694886] J Biol Chem. 2000 Mar 17;275(11):7447-50 [10713043] Eur J Immunol. 1999 Oct;29(10):3122-32 [10540323] Immunity. 1996 Jan;4(1):57-65 [8574852] J Immunol. 1996 Apr 1;156(7):2642-52 [8786330] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2941-6 [8610147] Genetics. 1997 Dec;147(4):1557-68 [9409821] Mol Gen Genet. 1998 Apr;257(6):686-92 [9604893] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6953-8 [9618520] Immunity. 1998 Jul;9(1):105-14 [9697840] Immunity. 1998 Jul;9(1):135-41 [9697843] Mol Cell Biol. 1999 Jan;19(1):147-54 [9858539] Immunity. 1998 Dec;9(6):859-69 [9881976] Science. 1999 Feb 12;283(5404):1001-4 [9974380] J Biol Chem. 1999 May 14;274(20):13741-3 [10318775] J Immunol. 1999 Jun 1;162(11):6596-601 [10352276] EMBO J. 1999 Jun 15;18(12):3491-501 [10369688] Nature. 1999 Jun 17;399(6737):700-4 [10385124] Science. 1999 Jul 9;285(5425):263-5 [10398605] Genetics. 1999 Aug;152(4):1249-67 [10430556] Genomics. 1999 Aug 15;60(1):20-30 [10458907] Genes Dev. 1999 Sep 1;13(17):2191-5 [10485842] J Biol Chem. 2000 Feb 11;275(6):4460-6 [10660619] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiovascular responses to scalp infiltration with different concentrations of epinephrine with or without lidocaine during craniotomy. AN - 70879804; 11375836 AB - Intraoperative blood pressure changes alter cerebral blood flow in neurosurgical patients with impaired autoregulation. Infiltration of the scalp before craniotomy may cause hemodynamic changes that depend on the composition of the solution used. We investigated cardiovascular responses to infiltration of the scalp with five different combinations of epinephrine and lidocaine in 112 patients: Group A, lidocaine 0.5%; Group B, lidocaine 0.5% with epinephrine 1:200,000; Group C, lidocaine 0.5% with epinephrine 1:100,000; Group D, normal saline with epinephrine 1:200,000; and Group E, normal saline with epinephrine 1:100,000. Episodes of tachycardia occurred more frequently in group E (P = 0.03). Plain lidocaine did not cause any significant change in blood pressure. The incidence of systolic, diastolic, and mean arterial hypertension was significantly increased in group E (P < 0.01). Episodes of diastolic hypertension occurred more frequently in Group D (P < 0.01). A biphasic diastolic and mean arterial hypotension (around Minute 2 and Minutes 9-15) occurred in Groups C and B (P < 0.001). In conclusion, epinephrine 1:100,000 causes significant tachycardia. Epinephrine in concentrations of 1:100,000 and 1:200,000 causes significant hypertension. The combination of lidocaine and epinephrine attenuates the hypertension but results in a biphasic hypotensive response. JF - Anesthesia and analgesia AU - Murthy, H S AU - Rao, G S AD - Department of Neuroanaesthesia, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1516 EP - 1519 VL - 92 IS - 6 SN - 0003-2999, 0003-2999 KW - Anesthetics, Local KW - 0 KW - Vasoconstrictor Agents KW - Lidocaine KW - 98PI200987 KW - Epinephrine KW - YKH834O4BH KW - Abridged Index Medicus KW - Index Medicus KW - Hypertension -- prevention & control KW - Humans KW - Adult KW - Blood Pressure -- drug effects KW - Tachycardia -- chemically induced KW - Male KW - Female KW - Hemodynamics -- drug effects KW - Vasoconstrictor Agents -- pharmacology KW - Anesthetics, Local -- pharmacology KW - Epinephrine -- pharmacology KW - Vasoconstrictor Agents -- administration & dosage KW - Scalp -- physiology KW - Lidocaine -- pharmacology KW - Epinephrine -- administration & dosage KW - Craniotomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70879804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesia+and+analgesia&rft.atitle=Cardiovascular+responses+to+scalp+infiltration+with+different+concentrations+of+epinephrine+with+or+without+lidocaine+during+craniotomy.&rft.au=Murthy%2C+H+S%3BRao%2C+G+S&rft.aulast=Murthy&rft.aufirst=H&rft.date=2001-06-01&rft.volume=92&rft.issue=6&rft.spage=1516&rft.isbn=&rft.btitle=&rft.title=Anesthesia+and+analgesia&rft.issn=00032999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety of intra-arterial thrombolysis in the postoperative period. AN - 70879767; 11387500 AB - Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of postoperative strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of postoperative IAT. This was a retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality rates were determined. Death or complications directly related to IAT were determined. Thirty-six patients (median age, 71.5 years; range, 45 to 85) were identified. Median time from surgery to stroke was 21.5 hours (range, 1 to 120). Open heart surgery was done in 18 (50%), carotid endarterectomy in 6 (17%), craniotomy in 3 (8%), ophthalmologic-ear, nose and throat surgery in 2 (6%), urologic-gynecologic surgery in 4 (11%), orthopedic surgery in 2 (6%), and plastic surgery in 1 (3%). The stroke causes were cardioembolism in 24 (67%), large-vessel atherosclerosis in 4 (11%), dissection in 3 (8%), postendarterectomy occlusion in 4 (11%), and radiation arteriopathy in 1 (3%). Median time to angiogram was 2.5 hours (0.1 to 5.5). Occlusion sites were M1 in 19 (53%), M2 in 9 (25%), internal carotid artery in 5 (14%), basilar artery in 2 (6%), and posterior communicating artery in 1 (3%). Thrombolysis was completed at a median of 4.5 hours (range, 1 to 8.0). Tissue plasminogen activator was used in 19 (53%) and urokinase in 17 (47%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (25%) cases (minor in 6, major in 3). The major surgical bleeds were 2 post-craniotomy intracranial hemorrhages and 1 hemopericardium after coronary artery bypass grafting; all were fatal. Six deaths were non-IAT related: 3 caused by cerebral edema and 3 by systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (P<0.02). Postoperative IAT carries a risk of bleeding in up to 25% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality rate in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for postoperative strokes. JF - Stroke AU - Chalela, J A AU - Katzan, I AU - Liebeskind, D S AU - Rasmussen, P AU - Zaidat, O AU - Suarez, J I AU - Chiu, D AU - Klucznick, R P AU - Jauch, E AU - Cucchiara, B L AU - Saver, J AU - Kasner, S E AD - Department of Neurology, University of Pennsylvania, Philadelphia, USA. chalelaj@ninds.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1365 EP - 1369 VL - 32 IS - 6 KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Index Medicus KW - Severity of Illness Index KW - Infusions, Intra-Arterial KW - Dose-Response Relationship, Drug KW - Brain -- blood supply KW - Humans KW - Tomography, X-Ray Computed KW - Retrospective Studies KW - Aged KW - Postoperative Period KW - Surgical Procedures, Operative -- adverse effects KW - Tissue Plasminogen Activator -- administration & dosage KW - Brain -- diagnostic imaging KW - Postoperative Hemorrhage -- etiology KW - Urokinase-Type Plasminogen Activator -- administration & dosage KW - Aged, 80 and over KW - Brain -- pathology KW - Treatment Outcome KW - Middle Aged KW - Female KW - Male KW - Postoperative Complications -- drug therapy KW - Stroke -- drug therapy KW - Postoperative Complications -- prevention & control KW - Stroke -- diagnosis KW - Stroke -- prevention & control KW - Thrombolytic Therapy -- adverse effects KW - Postoperative Complications -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70879767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=Safety+of+intra-arterial+thrombolysis+in+the+postoperative+period.&rft.au=Chalela%2C+J+A%3BKatzan%2C+I%3BLiebeskind%2C+D+S%3BRasmussen%2C+P%3BZaidat%2C+O%3BSuarez%2C+J+I%3BChiu%2C+D%3BKlucznick%2C+R+P%3BJauch%2C+E%3BCucchiara%2C+B+L%3BSaver%2C+J%3BKasner%2C+S+E&rft.aulast=Chalela&rft.aufirst=J&rft.date=2001-06-01&rft.volume=32&rft.issue=6&rft.spage=1365&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=1524-4628&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that reduction of hepatocyte growth factor (HGF) is not required for peroxisome proliferator-induced hepatocyte proliferation. AN - 70877970; 11375907 AB - The mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis are not understood. Because of the uncertainty of human cancer risk associated with peroxisome proliferators, delineating the mechanisms of carcinogenesis by these agents is of great interest. Alterations in liver growth factors were postulated to contribute to the carcinogenic effect of peroxisome proliferators. Administration of these compounds to rodents results in down-regulation of hepatocyte growth factor (HGF) and supplementing culture medium with HGF is reported to suppress cell proliferation of preneoplastic and neoplastic cells from WY-14,643-treated livers. Combined, these observations suggest that reduced levels of hepatic HGF contribute to the mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis. To determine if HGF can prevent the effects of peroxisome proliferators in liver, the short-term influence of WY-14,643 in two different lines of HGF transgenic mice was examined. Mice were fed either a control diet or one containing 0.1% WY-14-643 for one week. Hepatomegaly was found in both HGF transgenic mouse lines fed WY-14,643 compared with controls. Additionally, hepatic expression of typical mRNA markers of peroxisome proliferation including those encoding peroxisomal fatty acid metabolizing enzymes and cell cycle control proteins were all significantly elevated in HGF transgenic mice fed WY-14,643 compared with controls. Down-regulation of HGF was found to be dependent on PPARalpha since lower levels of HGF mRNA and protein were observed in wild-type mice fed WY-14,643 for 1 week and not in similarly treated PPARalpha-null mice. These results demonstrate that the early increase in hepatic mRNAs associated with peroxisome and cell proliferation induced by WY-14,643 treatment can not be prevented by overexpression of HGF in vivo. JF - Carcinogenesis AU - Kiss, A AU - Ortiz-Aguayo, R AU - Sharp, R AU - Merlino, G AU - Thorgeirsson, S S AU - Gonzalez, F J AU - Peters, J M AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 975 EP - 979 VL - 22 IS - 6 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Peroxisome Proliferators KW - Pyrimidines KW - RNA, Messenger KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - pirinixic acid KW - 86C4MRT55A KW - Index Medicus KW - Animals KW - RNA, Messenger -- metabolism KW - Pyrimidines -- toxicity KW - Humans KW - Cell Division -- drug effects KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Hepatocyte Growth Factor -- physiology KW - Hepatocytes -- drug effects KW - Hepatocyte Growth Factor -- genetics KW - Peroxisome Proliferators -- toxicity KW - Hepatocyte Growth Factor -- metabolism KW - Hepatocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70877970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Evidence+that+reduction+of+hepatocyte+growth+factor+%28HGF%29+is+not+required+for+peroxisome+proliferator-induced+hepatocyte+proliferation.&rft.au=Kiss%2C+A%3BOrtiz-Aguayo%2C+R%3BSharp%2C+R%3BMerlino%2C+G%3BThorgeirsson%2C+S+S%3BGonzalez%2C+F+J%3BPeters%2C+J+M&rft.aulast=Kiss&rft.aufirst=A&rft.date=2001-06-01&rft.volume=22&rft.issue=6&rft.spage=975&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. AN - 70877886; 11279102 AB - Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with members of the transforming growth factor-beta family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of TbetaRII. Of the type I receptors, SNX6 was found to interact only with inactivated TbetaRI. SNXs 1-4 also interacted with the transforming growth factor-beta receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases. JF - The Journal of biological chemistry AU - Parks, W T AU - Frank, D B AU - Huff, C AU - Renfrew Haft, C AU - Martin, J AU - Meng, X AU - de Caestecker, M P AU - McNally, J G AU - Reddi, A AU - Taylor, S I AU - Roberts, A B AU - Wang, T AU - Lechleider, R J AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, the Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 19332 EP - 19339 VL - 276 IS - 22 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Epitopes KW - Ligands KW - RNA, Messenger KW - SNX6 protein, human KW - Sorting Nexins KW - Transforming Growth Factor beta KW - Vesicular Transport Proteins KW - Luciferases KW - EC 1.13.12.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - COS Cells KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Two-Hybrid System Techniques KW - Luciferases -- metabolism KW - Amino Acid Sequence KW - Tissue Distribution KW - Precipitin Tests KW - Protein Binding KW - Cloning, Molecular KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Transfection KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Signal Transduction KW - Cell Line KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Transforming Growth Factor beta -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70877886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Sorting+nexin+6%2C+a+novel+SNX%2C+interacts+with+the+transforming+growth+factor-beta+family+of+receptor+serine-threonine+kinases.&rft.au=Parks%2C+W+T%3BFrank%2C+D+B%3BHuff%2C+C%3BRenfrew+Haft%2C+C%3BMartin%2C+J%3BMeng%2C+X%3Bde+Caestecker%2C+M+P%3BMcNally%2C+J+G%3BReddi%2C+A%3BTaylor%2C+S+I%3BRoberts%2C+A+B%3BWang%2C+T%3BLechleider%2C+R+J&rft.aulast=Parks&rft.aufirst=W&rft.date=2001-06-01&rft.volume=276&rft.issue=22&rft.spage=19332&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-05-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of HIF-1- and wild-type p53-stimulated transcription by codon Arg175 p53 mutants with selective loss of functions. AN - 70873283; 11375890 AB - Overexpression of ectopic mutant p53 represses wild-type p53-stimulated transcription, known as a dominant negative effect. On the other hand, overexpression of wild-type p53 can repress transcription stimulated by several transcription factors, including hypoxia-inducible factor-1 (HIF-1). Using a panel of well-characterized Arg175 p53 mutants we found that only mutants (Tyr175, Trp175, Asp175 and Phe175) which have completely lost their ability to transactivate repress wild-type p53-stimulated Bax, p21 and PG13 promoter constructs. In contrast, Asn175, Gln175, Leu175 and Pro175 mutants which partially retained transactivating functions did not exert dominant negative effects against PG13 and p21 promoter constructs. However, these latter mutants failed to activate Bax and, instead, exerted a dominant negative effect on a Bax-Luc promoter construct. We conclude that a dominant negative effect is promoter selective as a consequence of selective loss of transactivating function. Albeit less potent than wild-type p53, all Arg175 p53 mutants retained partial ability to repress HIF-1-stimulated transcription. We propose that transrepression and the dominant negative effect have similar mechanisms and may involve competition with transcription factors (wild-type p53, HIF-1, etc.) for cofactors such as p300. Thus, a p53(22/23) mutant, which is deficient in p300 binding, did not exert dominant negative effects. Like transrepression, the dominant negative effect required overexpression of mutant p53 and, therefore, is not dominant. In the presence of a wild-type p53 allele, levels of endogenous mutant p53 protein were low in heterozygous cells. Endogenous mutant p53 became overexpressed only after loss of the second p53 allele. Therefore, endogenous mutant p53s are unable to display a dominant negative effect. This explains why loss of the second p53 allele is required to eliminate p53 functions in cancer cells. JF - Carcinogenesis AU - Blagosklonny, M V AU - Giannakakou, P AU - Romanova, L Y AU - Ryan, K M AU - Vousden, K H AU - Fojo, T AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. mikhailb@box-m.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 861 EP - 867 VL - 22 IS - 6 SN - 0143-3334, 0143-3334 KW - BAX protein, human KW - 0 KW - CDKN1A protein, human KW - Codon KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Arginine KW - 94ZLA3W45F KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Codon -- genetics KW - Humans KW - Prostatic Neoplasms -- genetics KW - Transcription, Genetic KW - Binding Sites KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Arginine -- genetics KW - Substrate Specificity KW - Consensus Sequence KW - Proto-Oncogene Proteins -- genetics KW - Cyclins -- genetics KW - Female KW - Male KW - Tumor Suppressor Protein p53 -- physiology KW - Nuclear Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - Nuclear Proteins -- antagonists & inhibitors KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Transcriptional Activation -- physiology KW - DNA-Binding Proteins -- antagonists & inhibitors KW - DNA-Binding Proteins -- physiology KW - Tumor Suppressor Protein p53 -- genetics KW - Mutation KW - Nuclear Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70873283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Inhibition+of+HIF-1-+and+wild-type+p53-stimulated+transcription+by+codon+Arg175+p53+mutants+with+selective+loss+of+functions.&rft.au=Blagosklonny%2C+M+V%3BGiannakakou%2C+P%3BRomanova%2C+L+Y%3BRyan%2C+K+M%3BVousden%2C+K+H%3BFojo%2C+T&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2001-06-01&rft.volume=22&rft.issue=6&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rigidity of circulating lymphocytes is primarily conferred by vimentin intermediate filaments. AN - 70865435; 11359818 AB - Lymphocytes need rigidity while in circulation, but must abruptly become deformable to undergo transmigration into tissue. Previously, the control of leukocyte deformability has been attributed to microfilaments or microtubules, but the present studies demonstrate the greater importance of vimentin intermediate filaments (IFs). In circulating T lymphocytes, IFs form a distinctive spherical cage that undergoes a rapid condensation into a juxtanuclear aggregate during chemokine-induced polarization. Measurements of the resistance of peripheral blood T lymphocytes to global deformation demonstrate that their rigidity is primarily dependent on intact vimentin filaments. Microtubules, in contrast, are not sufficient to maintain rigidity. Thus, vimentin IFs are a primary source of structural support in circulating human lymphocytes, and their regulated collapse is likely to be an essential element in chemokine-induced transendothelial migration. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Brown, M J AU - Hallam, J A AU - Colucci-Guyon, E AU - Shaw, S AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 6640 EP - 6646 VL - 166 IS - 11 SN - 0022-1767, 0022-1767 KW - Oxazoles KW - 0 KW - Vimentin KW - calyculin A KW - 7D07U14TK3 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cell Size -- physiology KW - Humans KW - Interphase -- physiology KW - Mice KW - Cell Membrane -- physiology KW - Cell Separation KW - Mice, Knockout KW - Cell Size -- drug effects KW - Cell Polarity -- physiology KW - Mice, Inbred Strains KW - Oxazoles -- pharmacology KW - Cells, Cultured KW - Stress, Mechanical KW - Cell Nucleus -- physiology KW - T-Lymphocytes -- cytology KW - Vimentin -- biosynthesis KW - Blood Circulation -- immunology KW - Cell Movement -- physiology KW - Blood Circulation -- physiology KW - Vimentin -- blood KW - T-Lymphocytes -- physiology KW - Intermediate Filaments -- physiology KW - T-Lymphocytes -- drug effects KW - Vimentin -- physiology KW - Vimentin -- genetics KW - Intermediate Filaments -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70865435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Rigidity+of+circulating+lymphocytes+is+primarily+conferred+by+vimentin+intermediate+filaments.&rft.au=Brown%2C+M+J%3BHallam%2C+J+A%3BColucci-Guyon%2C+E%3BShaw%2C+S&rft.aulast=Brown&rft.aufirst=M&rft.date=2001-06-01&rft.volume=166&rft.issue=11&rft.spage=6640&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone. AN - 70864215; 11278302 AB - Members of the transforming growth factor-beta (TGF-beta) superfamily signal through unique cell membrane receptor serine-threonine kinases to activate downstream targets. TRAP1 is a previously described 96-kDa cytoplasmic protein shown to bind to TGF-beta receptors and suggested to play a role in TGF-beta signaling. We now fully characterize the binding properties of TRAP1, and show that it associates strongly with inactive heteromeric TGF-beta and activin receptor complexes and is released upon activation of signaling. Moreover, we demonstrate that TRAP1 plays a role in the Smad-mediated signal transduction pathway, interacting with the common mediator, Smad4, in a ligand-dependent fashion. While TRAP1 has only a small stimulatory effect on TGF-beta signaling in functional assays, deletion constructs of TRAP1 inhibit TGF-beta signaling and diminish the interaction of Smad4 with Smad2. These are the first data to identify a specific molecular chaperone for Smad4, suggesting a model in which TRAP1 brings Smad4 into the vicinity of the receptor complex and facilitates its transfer to the receptor-activated Smad proteins. JF - The Journal of biological chemistry AU - Wurthner, J U AU - Frank, D B AU - Felici, A AU - Green, H M AU - Cao, Z AU - Schneider, M D AU - McNally, J G AU - Lechleider, R J AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis and Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 19495 EP - 19502 VL - 276 IS - 22 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Epitopes KW - Intracellular Signaling Peptides and Proteins KW - Ligands KW - Luminescent Proteins KW - Molecular Chaperones KW - SMAD2 protein, human KW - SMAD4 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad4 Protein KW - Smad4 protein, mouse KW - TGFBRAP1 protein, human KW - Trans-Activators KW - Transforming Growth Factor beta KW - Activins KW - 104625-48-1 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Inhibins KW - 57285-09-3 KW - Index Medicus KW - Animals KW - COS Cells KW - Molecular Chaperones -- metabolism KW - Humans KW - Transcription, Genetic KW - Models, Biological KW - Microscopy, Fluorescence KW - Inhibins -- metabolism KW - Cytoplasm -- metabolism KW - Genes, Reporter KW - Epitopes -- metabolism KW - Signal Transduction KW - Immunoblotting KW - Protein Biosynthesis KW - Plasmids -- metabolism KW - Luminescent Proteins -- metabolism KW - Mice KW - Precipitin Tests KW - Protein Binding KW - Gene Deletion KW - Transfection KW - Protein Structure, Tertiary KW - Transforming Growth Factor beta -- metabolism KW - Cell Line KW - Trans-Activators -- metabolism KW - Carrier Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70864215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transforming+growth+factor-beta+receptor-associated+protein+1+is+a+Smad4+chaperone.&rft.au=Wurthner%2C+J+U%3BFrank%2C+D+B%3BFelici%2C+A%3BGreen%2C+H+M%3BCao%2C+Z%3BSchneider%2C+M+D%3BMcNally%2C+J+G%3BLechleider%2C+R+J%3BRoberts%2C+A+B&rft.aulast=Wurthner&rft.aufirst=J&rft.date=2001-06-01&rft.volume=276&rft.issue=22&rft.spage=19495&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-05-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of practice-dependent plasticity in human motor cortex. AN - 70863780; 11353733 AB - Motor practice may lead to expansion of trained representations in the motor cortex, but it is unknown whether this practice-dependent plasticity can be purposefully enhanced or depressed. Evidence, mainly based on animal experiments, indicates that the activity of GABA-related cortical inhibition is important in controlling the extent to which plasticity may occur. We tested the role of GABA in modulating practice-dependent plasticity in the human motor cortex. A decrease in GABA-related cortical inhibition was achieved by ischaemic nerve block (INB) in the hand by deafferentation/deefferentation and an increase was achieved by administration of the GABA(A) receptor agonist lorazepam. In Experiment 1, healthy subjects performed motor practice (MP), consisting of repeated ballistic contractions of the biceps muscle in the absence (MP alone) or presence of INB (MP+INB). Changes in the biceps motor cortex representation were assessed by transcranial magnetic stimulation (TMS). MP+INB resulted in a dramatic increase in the size of the motor evoked potential (MEP) and in paired-pulse excitability compared with mild or no changes in the MP-alone and INB-alone conditions. In Experiment 2, this dramatic increase in biceps representation induced by MP+INB was replicated when subjects were pretreated with placebo, but this increase was prevented or even switched to a decrease when subjects were pretreated with lorazepam. These findings indicate that a decrease in GABA-related inhibition facilitates practice-dependent plasticity in the human motor cortex, whereas an increase depresses it. In Experiment 3, practice-dependent plasticity (assessed by TMS, as in the first two experiments) was also tested at the behavioural level. The dramatic increase in biceps MEP size induced by MP+INB was paralleled by an increase in peak acceleration of the fastest elbow flexion movements. Similarly, the lack of change in MEP size in the MP-alone condition was paralleled by a lack of change in peak acceleration. We propose that changes in GABA activity may be instrumented to modulate plasticity purposefully; for instance, to enhance plastic change and recovery of function after a lesion in neurological patients. JF - Brain : a journal of neurology AU - Ziemann, U AU - Muellbacher, W AU - Hallett, M AU - Cohen, L G AD - Clinic of Neurology, J. W. Goethe University, Schleusenweg 2-16, D-60590 Frankfurt am Main, Germany. ziemann@codon.nih.gov Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 1171 EP - 1181 VL - 124 SN - 0006-8950, 0006-8950 KW - GABA Modulators KW - 0 KW - GABA-A Receptor Agonists KW - Receptors, GABA-A KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Lorazepam KW - O26FZP769L KW - Abridged Index Medicus KW - Index Medicus KW - Evoked Potentials, Motor -- drug effects KW - Nerve Block -- adverse effects KW - Magnetics KW - Muscle, Skeletal -- physiology KW - Humans KW - Muscle, Skeletal -- innervation KW - Electromyography KW - Electric Stimulation KW - Lorazepam -- administration & dosage KW - Biomechanical Phenomena KW - Movement -- physiology KW - Adult KW - GABA Modulators -- adverse effects KW - Receptors, GABA-A -- metabolism KW - Evoked Potentials, Motor -- physiology KW - GABA Modulators -- administration & dosage KW - Movement -- drug effects KW - Lorazepam -- adverse effects KW - Motor Cortex -- cytology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neuronal Plasticity -- physiology KW - Neural Inhibition -- drug effects KW - Physical Fitness -- physiology KW - Motor Cortex -- metabolism KW - Neural Inhibition -- physiology KW - Motor Cortex -- drug effects KW - Motor Skills -- physiology KW - Motor Skills -- drug effects KW - Neurons -- cytology KW - Neuronal Plasticity -- drug effects KW - gamma-Aminobutyric Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70863780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+%3A+a+journal+of+neurology&rft.atitle=Modulation+of+practice-dependent+plasticity+in+human+motor+cortex.&rft.au=Ziemann%2C+U%3BMuellbacher%2C+W%3BHallett%2C+M%3BCohen%2C+L+G&rft.aulast=Ziemann&rft.aufirst=U&rft.date=2001-06-01&rft.volume=124&rft.issue=&rft.spage=1171&rft.isbn=&rft.btitle=&rft.title=Brain+%3A+a+journal+of+neurology&rft.issn=00068950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of induction of cytochrome p450 enzymes by the proestrogenic endocrine disruptor pesticide-methoxychlor: interactions of methoxychlor metabolites with the constitutive androstane receptor system. AN - 70862620; 11353743 AB - Methoxychlor, a structural analog of the DDT pesticide, was previously shown to induce rat hepatic CYP2B and -3A mRNAs and the corresponding proteins [J Biochem Mol Toxicol 1998;12:315-323], Additionally, methoxychlor was found to activate the constitutive androstane receptor (CAR) system and induce CYP2B6 (J Biol Chem 1999;274:6043-6046), suggesting a mechanism for methoxychlor-mediated cytochrome P450 (P450) 2B induction. However, it has not been established whether CAR activation and P450 induction was due to methoxychlor per se and/or due to its metabolites. Also, a possible link between the estrogenic potency of methoxychlor metabolites and CAR activation or P450 induction was not investigated. The current study explores the ability of methoxychlor and its metabolites to activate CAR and whether their potency of CAR activation correlates with their respective estrogenicity. Methoxychlor and its metabolites [mono-OH-M [1,1,1-trichloro-2 (4-hydroxyphenyl)-2'-(4-methoxyphenyl)ethane]; bis-OH-M [1,1,1-trichloro-2,2'-bis(4-hydroxyphenyl)ethane]; ring-OH-M [1,1,1-trichloro-2(4-methoxyphenyl)-2'-(3-hydroxy-4-methoxyphenyl)ethane]; and tris-OH-M [1,1,1-trichloro-2(4-hydroxyphenyl)-2'-(3,4-dihydroxyphenyl)ethane]] were found to be potent activators of CAR. Dose response curves indicated that tris-OH-M is a more potent CAR activator than methoxychlor, mono-OH-M, and bis-OH-M. Since tris-OH-M is a much weaker estrogen receptor-alpha agonist than mono-OH-M and bis-OH-M, it seems that estrogenicity is not a significant factor in CAR activation. These findings indicate that alteration of methoxychlor-benzene rings, i.e., generation of phenolic constituents, does not appreciably alter CAR activation and suggest that a common structural motif in the methoxychlor class of compounds controls CAR activation. Studies are needed to identify the structural motif necessary for CAR activation and CYP2B induction. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Blizard, D AU - Sueyoshi, T AU - Negishi, M AU - Dehal, S S AU - Kupfer, D AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 781 EP - 785 VL - 29 IS - 6 SN - 0090-9556, 0090-9556 KW - Androstanes KW - 0 KW - Estrogens, Non-Steroidal KW - Insecticides KW - Receptors, Androgen KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - androstane KW - KT649U81FE KW - Methoxychlor KW - RIA79UD69L KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Enzyme Induction KW - Male KW - Methoxychlor -- metabolism KW - Androstanes -- metabolism KW - Endocrine Glands -- drug effects KW - Receptors, Androgen -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Methoxychlor -- pharmacology KW - Estrogens, Non-Steroidal -- pharmacology KW - Insecticides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70862620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Mechanism+of+induction+of+cytochrome+p450+enzymes+by+the+proestrogenic+endocrine+disruptor+pesticide-methoxychlor%3A+interactions+of+methoxychlor+metabolites+with+the+constitutive+androstane+receptor+system.&rft.au=Blizard%2C+D%3BSueyoshi%2C+T%3BNegishi%2C+M%3BDehal%2C+S+S%3BKupfer%2C+D&rft.aulast=Blizard&rft.aufirst=D&rft.date=2001-06-01&rft.volume=29&rft.issue=6&rft.spage=781&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of telomerase activity during development of human mast cells from peripheral blood CD34+ cells: comparisons with tumor mast-cell lines. AN - 70862425; 11359819 AB - To further characterize the development of mast cells from human hemopoietic pluripotent cells we have investigated the expression of telomerase activity in cultured human peripheral blood CD34+ cells, and CD34+ /CD117+ /CD13+ progenitor mast cells selected therefrom, with the idea that induction of telomerase is associated with clonal expansion of CD34+ /CD117+ /CD13+ cells. A rapid increase in telomerase activity preceded proliferation of both populations of cells in the presence of stem cell factor and either IL-3 or IL-6. The induction was transient, and telomerase activity declined to basal levels well before the appearance of mature mast cells. Studies with pharmacologic inhibitors suggested that this induction was initially dependent on the p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase, but once cell replication was underway telomerase activity, but not cell replication, became resistant to the effects of inhibitors. Tumor mast cell lines, in contrast, expressed persistently high telomerase activity throughout the cell cycle, and this expression was unaffected by inhibitors of all known signaling pathways in mast cells even when cell proliferation was blocked for extended periods. These results suggest that the transient induction of telomerase activity in human progenitor mast cells was initially dependent on growth factor-mediated signals, whereas maintenance of high activity in tumor mast cell lines was not dependent on intracellular signals or cell replication. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Chaves-Dias, C AU - Hundley, T R AU - Gilfillan, A M AU - Kirshenbaum, A S AU - Cunha-Melo, J R AU - Metcalfe, D D AU - Beaven, M A AD - Laboratory of Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 6647 EP - 6656 VL - 166 IS - 11 SN - 0022-1767, 0022-1767 KW - Acetamides KW - 0 KW - Androstadienes KW - Antigens, CD34 KW - Enzyme Inhibitors KW - Growth Inhibitors KW - Growth Substances KW - Imidazoles KW - Interleukin-3 KW - Interleukin-6 KW - Protein Kinase Inhibitors KW - Protein Synthesis Inhibitors KW - Pyridines KW - Stem Cell Factor KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - Telomerase KW - EC 2.7.7.49 KW - Antigens, CD13 KW - EC 3.4.11.2 KW - hexamethylene bisacetamide KW - LA133J59VU KW - 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole KW - PVX798P8GI KW - wortmannin KW - XVA4O219QW KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Imidazoles -- pharmacology KW - Humans KW - Interleukin-3 -- pharmacology KW - Interleukin-6 -- pharmacology KW - Rats KW - Tumor Cells, Cultured KW - Enzyme Induction -- drug effects KW - Stem Cell Factor -- pharmacology KW - Enzyme Activation -- drug effects KW - Drug Synergism KW - Cell Differentiation -- drug effects KW - Antigens, CD13 -- biosynthesis KW - Cell Division -- drug effects KW - Androstadienes -- pharmacology KW - Acetamides -- pharmacology KW - Protein Synthesis Inhibitors -- pharmacology KW - Cells, Cultured KW - Growth Substances -- pharmacology KW - Growth Inhibitors -- pharmacology KW - Proto-Oncogene Proteins c-kit -- biosynthesis KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Activation -- immunology KW - Pyridines -- pharmacology KW - Cell Line KW - Cell Cycle -- drug effects KW - Telomerase -- antagonists & inhibitors KW - Mast Cells -- immunology KW - Leukemia, Basophilic, Acute -- immunology KW - Leukemia, Basophilic, Acute -- pathology KW - Antigens, CD34 -- biosynthesis KW - Mast Cells -- enzymology KW - Telomerase -- biosynthesis KW - Leukemia, Basophilic, Acute -- enzymology KW - Mast Cells -- cytology KW - Telomerase -- metabolism KW - Mast Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70862425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Induction+of+telomerase+activity+during+development+of+human+mast+cells+from+peripheral+blood+CD34%2B+cells%3A+comparisons+with+tumor+mast-cell+lines.&rft.au=Chaves-Dias%2C+C%3BHundley%2C+T+R%3BGilfillan%2C+A+M%3BKirshenbaum%2C+A+S%3BCunha-Melo%2C+J+R%3BMetcalfe%2C+D+D%3BBeaven%2C+M+A&rft.aulast=Chaves-Dias&rft.aufirst=C&rft.date=2001-06-01&rft.volume=166&rft.issue=11&rft.spage=6647&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic induction of apoptosis by the combination of trail and chemotherapy in chemoresistant ovarian cancer cells. AN - 70853420; 11371126 AB - The aim of this study was to investigate whether TNF-related apoptosis-inducing ligand (TRAIL) alone or in combination with chemotherapy could induce apoptosis in ovarian cancer cells resistant to chemotherapy. Twelve chemoresistant epithelial cancer cell lines were treated with each chemotherapeutic drug alone (cisplatin, doxorubicin, or paclitaxel), TRAIL alone, or the combination. Toxicity was assessed using the MTS assay. To assess whether growth inhibition was due to apoptosis, TUNEL assay, caspase activation (measured by caspase-3 and PARP cleavage), and the sub G0/G1 fraction of cells were measured. Synergism was confirmed by fractional inhibition and dose-effect analysis. Expression of death and decoy receptors was studied by immunoblotting and an RNase protection assay. Statistical comparison of means was performed using Student's t test. The majority of the chemoresistant cells were also resistant to TRAIL alone. In contrast, the combination of TRAIL and chemotherapy resulted in a significant growth inhibition over a wide range of concentrations. This interaction was synergistic by dose-effect analysis. Flow cytometry demonstrated a significant increase in the fraction of apoptotic cells by the combination compared to each reagent alone. A significant enhancement in caspase and PARP cleavage was observed upon treatment with the combination. Finally, no correlation between induction of apoptosis and level of death receptors was found. The data suggest that almost all the ovarian cancer cells, which are resistant to chemotherapy, are also resistant to TRAIL. The combination of TRAIL and chemotherapy overcomes this resistance in a synergistic fashion by triggering caspase-mediated apoptosis. The combination of TRAIL and chemotherapy could be useful as a therapy for chemoresistant ovarian cancers. Copyright 2001 Academic Press. JF - Gynecologic oncology AU - Cuello, M AU - Ettenberg, S A AU - Nau, M M AU - Lipkowitz, S AD - Genetics Department, National Cancer Institute, Bethesda, Maryland 20889, USA. Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 380 EP - 390 VL - 81 IS - 3 SN - 0090-8258, 0090-8258 KW - Antineoplastic Agents KW - 0 KW - Apoptosis Regulatory Proteins KW - Membrane Glycoproteins KW - RNA, Messenger KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - Receptors, Tumor Necrosis Factor KW - Recombinant Fusion Proteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFRSF10A protein, human KW - TNFRSF10B protein, human KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Doxorubicin KW - 80168379AG KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Humans KW - Drug Resistance, Neoplasm KW - Paclitaxel -- pharmacology KW - RNA, Messenger -- genetics KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Caspases -- metabolism KW - RNA, Messenger -- biosynthesis KW - Recombinant Fusion Proteins -- administration & dosage KW - Drug Resistance, Multiple KW - Cisplatin -- administration & dosage KW - Tumor Cells, Cultured KW - Doxorubicin -- pharmacology KW - Cisplatin -- pharmacology KW - Drug Synergism KW - Receptors, Tumor Necrosis Factor -- genetics KW - Cell Division -- drug effects KW - Doxorubicin -- administration & dosage KW - Receptors, Tumor Necrosis Factor -- biosynthesis KW - Recombinant Fusion Proteins -- pharmacology KW - Female KW - Ovarian Neoplasms -- metabolism KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Ovarian Neoplasms -- pathology KW - Apoptosis -- physiology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Membrane Glycoproteins -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Ovarian Neoplasms -- drug therapy KW - Membrane Glycoproteins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70853420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Synergistic+induction+of+apoptosis+by+the+combination+of+trail+and+chemotherapy+in+chemoresistant+ovarian+cancer+cells.&rft.au=Cuello%2C+M%3BEttenberg%2C+S+A%3BNau%2C+M+M%3BLipkowitz%2C+S&rft.aulast=Cuello&rft.aufirst=M&rft.date=2001-06-01&rft.volume=81&rft.issue=3&rft.spage=380&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression. AN - 70832634; 11343207 AB - A human immunodeficiency virus (HIV) type 1-transgenic mouse line (166) that previously showed up-regulated expression of viral proteins and infectious particles after infection with pathogenic agents was tested as a model for screening the in vitro and in vivo efficacy of inhibitors of HIV-1 immune activation. Two types of interventions were assessed: use of either the immunosuppressive drug prednisolone or an HIV-1 envelope-targeted toxin (sCD4-PE40). Both agents inhibited lipopolysaccharide-induced p24 expression by splenocytes in vitro and, when administered to transgenic mice, suppressed the induction of plasma p24, as well as the ex vivo production of p24 and infectious virus stimulated by in vivo infection with Mycobacterium avium. Moreover, HIV-1 mRNA levels in the spleen were greatly reduced in mice treated with either agent. Because HIV-1 expression cannot be induced in T lymphocytes from line 166 mice, this model may be of particular advantage for testing interventions that target virus production by non-T cell virus reservoirs. JF - The Journal of infectious diseases AU - Schito, M L AU - Kennedy, P E AU - Kowal, R P AU - Berger, E A AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. mschito@niaid.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 1592 EP - 1600 VL - 183 IS - 11 SN - 0022-1899, 0022-1899 KW - Anti-HIV Agents KW - 0 KW - Antigens, CD4 KW - CD4-Pseudomonas toxin KW - Exotoxins KW - Glucocorticoids KW - HIV Core Protein p24 KW - Immunotoxins KW - Lipopolysaccharides KW - RNA, Messenger KW - RNA, Viral KW - Recombinant Proteins KW - Prednisolone KW - 9PHQ9Y1OLM KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Mycobacterium avium KW - Humans KW - Antigens, CD4 -- administration & dosage KW - Mice, Transgenic KW - Spleen -- virology KW - Spleen -- drug effects KW - Recombinant Proteins -- administration & dosage KW - Exotoxins -- pharmacology KW - Exotoxins -- administration & dosage KW - Recombinant Proteins -- pharmacology KW - HIV Core Protein p24 -- blood KW - Dose-Response Relationship, Drug KW - RNA, Messenger -- analysis KW - Mice KW - Immunotoxins -- administration & dosage KW - Glucocorticoids -- pharmacology KW - Cells, Cultured KW - Prednisolone -- pharmacology KW - Glucocorticoids -- administration & dosage KW - Antigens, CD4 -- pharmacology KW - RNA, Viral -- genetics KW - Immunotoxins -- pharmacology KW - Prednisolone -- administration & dosage KW - HIV-1 -- genetics KW - HIV Infections -- blood KW - HIV-1 -- isolation & purification KW - Anti-HIV Agents -- pharmacology KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- administration & dosage KW - HIV Infections -- microbiology KW - Proviruses -- drug effects KW - Proviruses -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70832634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+human+immunodeficiency+virus-transgenic+mouse+model+for+assessing+interventions+that+block+microbial-induced+proviral+expression.&rft.au=Schito%2C+M+L%3BKennedy%2C+P+E%3BKowal%2C+R+P%3BBerger%2C+E+A%3BSher%2C+A&rft.aulast=Schito&rft.aufirst=M&rft.date=2001-06-01&rft.volume=183&rft.issue=11&rft.spage=1592&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Political Contacts: Analyzing the Role of Similarity in Theories of Prejudice AN - 60393970; 200118383 AB - Over the last 50 years, many theories of prejudice reduction in social psychology have embraced the premise that intergroup contact allows people to recognize similarities between themselves, & that this perceived similarity overwhelms the social distance associated with intergroup antipathy. Given the mixed empirical evidence, however, we suggest that the positive effects of perceived similarity have been overemphasized. Although similarity may be sufficient for improved intergroup relations, the relationship between similarity & intergroup relations is far more complex than the literature usually suggests. Moreover, studying difference in intergroup contexts may yield new ways to resolve intergroup conflict & address group inequalities. 54 References. Adapted from the source document. JF - Political Psychology AU - Brown, Lisa M AU - Lopez, Gretchen E AD - NIMH Center Study Emotion & Attention, U Florida, Gainesville Y1 - 2001/06// PY - 2001 DA - June 2001 SP - 279 EP - 292 VL - 22 IS - 2 SN - 0162-895X, 0162-895X KW - Social Distance KW - Racism KW - Prejudice KW - Intergroup Relations KW - Psychological Theories KW - Social Psychology KW - article KW - 0312: social psychology; personality & social roles (individual traits, social identity, adjustment, conformism, & deviance) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60393970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Political+Psychology&rft.atitle=Political+Contacts%3A+Analyzing+the+Role+of+Similarity+in+Theories+of+Prejudice&rft.au=Brown%2C+Lisa+M%3BLopez%2C+Gretchen+E&rft.aulast=Brown&rft.aufirst=Lisa&rft.date=2001-06-01&rft.volume=22&rft.issue=2&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Political+Psychology&rft.issn=0162895X&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Social Psychology; Psychological Theories; Prejudice; Racism; Intergroup Relations; Social Distance ER - TY - JOUR T1 - Saving the Gash Delta, Sudan AN - 26991352; 200206-35-0172 (CE); 05179676 (EN) AB - This article looks at a seasonal river flooded irrigation system in eastern Sudan called the Gash Delta. The Gash Delta, as an irrigation system, has been managed since the 1900s, firstly by the Anglo-Egyptian colonial administration and currently by the Gash Delta Agricultural Corporation (GDAC). The Gash Delta supports a range of ethnic groups who have a diversity of production strategies, some of which are more successful than others. Since the 1980s, there has been a recognition of a breakdown of the irrigation system, illustrated by the declining surface areas available for agriculture and a general degradation of the physical production base. This has had negative impacts on the ethnic groups who rely on the Gash Delta for subsistence and livelihood. This paper examines the process of degradation and the looks at the possibility for rehabilitating the Gash Delta. JF - Land Degradation & Development [Land Degrad. Dev.] AU - Kirkby, J AD - Division of Geography & Environmental Management, Lipman Building, University of Northumbria at Newcastle, Newcastle-upon-Tyne, NEI 8ST, UK john.kirkby@unn.ac.uk PY - 2001 SP - 225 EP - 236 PB - John Wiley & Sons Ltd , Baffins Lane, Chichester, Sussex, PO19 1UD, UK, [mailto:cs-journals@wiley.co.uk], [URL:http://www.interscience.wiley.com] VL - 12 IS - 3 SN - 1085-3278, 1085-3278 KW - Civil Engineering (CE); Environmental Engineering (EN) KW - Irrigation systems KW - Land KW - Surface area KW - Agricultural management KW - Rivers KW - Article KW - EE 10:General Environmental Engineering (EN) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/26991352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvironmentalengabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Land+Degradation+%26+Development+%5BLand+Degrad.+Dev.%5D&rft.atitle=Saving+the+Gash+Delta%2C+Sudan&rft.au=Kirkby%2C+J&rft.aulast=Kirkby&rft.aufirst=J&rft.date=2001-06-01&rft.volume=12&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Land+Degradation+%26+Development+%5BLand+Degrad.+Dev.%5D&rft.issn=10853278&rft_id=info:doi/10.1002%2Fldr.435 LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Special Issue: Rethinking environment and development in Africa and Asia. N1 - Last updated - 2011-11-11 DO - http://dx.doi.org/10.1002/ldr.435 ER - TY - JOUR T1 - Recruiting a community sample in collaboration with farmworkers. AN - 21249650; 11703809 AB - Few studies have examined health effects of pesticides in farmworkers, possibly because researchers perceive this population to be relatively inaccessible. We conducted an epidemiologic study of health effects among farmworkers in two towns in central Florida--Apopka and Pierson. Apopka is a suburb of Orlando with a diffuse farmworker community working in many crops, whereas Pierson is a small rural town with a tightly knit farmworker community working mainly in ferns. We collaborated with the Farmworker Association of Florida, a grassroots organization representing 6,700 farmworker families. We identified potential participants using membership lists of the Community Trust Federal Credit Union. Members of the Farmworker Association served as recruiters for the study, locating randomly selected Credit Union members and administering a screening interview to determine eligibility. In Apopka 90% of contacted workers were screened, and 79% of eligible workers participated in the study; corresponding proportions in Pierson were 94 and 85%. Farmworkers who had worked for 6-15 years and those who worked in a defined type of agriculture (nursery, citrus, or ferns) were more likely to enroll than others. Thus, while the response rate was good for a multistage recruiting process, study participants had a slightly different work history from those who chose not to enroll. We conclude that it is possible to conduct a study of health outcomes in farmworkers with a defined population and good response rates. Collaboration with the community is essential to the success of such a project, and community characteristics can affect response rates. JF - Environmental Health Perspectives AU - Kamel, F AU - Moreno, T AU - Rowland, A S AU - Stallone, L AU - Ramirez-Garnica, G AU - Sandler, D P AD - National Institute of Environmental Health Sciences, 111 TW Alexander Dr., Research Triangle Park, NC 27709, USA., kamel@niehs.nih.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 457 EP - 459 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 109 IS - Suppl 3 SN - 0091-6765, 0091-6765 KW - Environment Abstracts KW - Historical account KW - suburbs KW - USA, Florida KW - towns KW - Pesticides KW - agriculture KW - USA, Florida, Orlando KW - ferns KW - Crops KW - Rural areas KW - ENA 06:Food & Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21249650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Recruiting+a+community+sample+in+collaboration+with+farmworkers.&rft.au=Kamel%2C+F%3BMoreno%2C+T%3BRowland%2C+A+S%3BStallone%2C+L%3BRamirez-Garnica%2C+G%3BSandler%2C+D+P&rft.aulast=Kamel&rft.aufirst=F&rft.date=2001-06-01&rft.volume=109&rft.issue=Suppl+3&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - suburbs; Historical account; towns; Pesticides; agriculture; ferns; Crops; Rural areas; USA, Florida; USA, Florida, Orlando ER - TY - JOUR T1 - Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) AN - 20938582; 11014313 AB - The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive-compulsive disorder (OCD) and-or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and-or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2-5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment. JF - International Journal of Neuropsychopharmacology AU - Leonard, Henrietta L AU - Swedo, Susan E AD - Pediatric and Developmental Neuropsychiatry Branch, NIMH, Bethesda, MD USA, Henrietta_Leonard@Brown.edu Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 191 EP - 198 PB - Cambridge University Press, 32 Avenue of the Americas New York NY 10013-2473 USA VL - 4 IS - 2 SN - 1461-1457, 1461-1457 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; CSA Neurosciences Abstracts KW - Obsessive-compulsive disorder KW - tic disorders KW - Tourette syndrome KW - streptococcal infection KW - basal ganglia disease KW - Streptococcus KW - Intravenous administration KW - Pediatrics KW - Brain KW - Autoimmunity KW - Antibiotics KW - Functional anatomy KW - Children KW - Immunomodulation KW - Environmental factors KW - Mental disorders KW - Structure-function relationships KW - Prophylaxis KW - Recurrent infection KW - Immune response KW - Obsessive compulsive disorder KW - Basal ganglia KW - Immunoglobulins KW - N3 11001:Behavioral and Cognitive Neuroscience KW - J 02350:Immunology KW - F 06930:Autoimmunity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20938582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Neuropsychopharmacology&rft.atitle=Paediatric+autoimmune+neuropsychiatric+disorders+associated+with+streptococcal+infection+%28PANDAS%29&rft.au=Leonard%2C+Henrietta+L%3BSwedo%2C+Susan+E&rft.aulast=Leonard&rft.aufirst=Henrietta&rft.date=2001-06-01&rft.volume=4&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Neuropsychopharmacology&rft.issn=14611457&rft_id=info:doi/doi%3A10.1017%2FS1461145701002371 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Intravenous administration; Pediatrics; Brain; Autoimmunity; Antibiotics; Functional anatomy; Children; Environmental factors; Immunomodulation; Mental disorders; Structure-function relationships; Prophylaxis; Recurrent infection; Immune response; Obsessive compulsive disorder; Basal ganglia; Immunoglobulins; Streptococcus DO - http://dx.doi.org/10.1017/S1461145701002371 ER - TY - JOUR T1 - Effects of short nap and exercise on elderly people having difficulty in sleeping AN - 20466990; 9152391 AB - AbstractThe purpose of the present study was to examine the effects of short nap and exercise on the sleep quality of elderly people who reported difficulty in sleeping. 'Interventions' such as short nap after lunch and moderate-intensity exercise in the evening were carried out for 4 weeks. After the 'interventions', wake time after sleep onset significantly decreased and sleep efficiency significantly increased, which showed that sleep quality was improved. The frequency of nodding in the evening significantly decreased. These results demonstrated that the proper awakening maintenance in the evening was effective in improving sleep quality. After the 'intervention', mental health was also improved with improving sleep quality. JF - Psychiatry and Clinical Neurosciences AU - Tanaka, Hideki AU - Taira, Kazuhiko AU - Arakawa, Masashi AU - Toguti, Hiroki AU - Urasaki, Chisae AU - Yamamoto, Yukari AU - Uezu, Eiko AU - Hori, Tadao AU - Shirakawa, Shuichiro AD - 1Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawashi, Chiba, Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 173 EP - 174 PB - Blackwell Publishing Ltd., 9600 Garsington Road VL - 55 IS - 3 SN - 1323-1316, 1323-1316 KW - Physical Education Index; CSA Neurosciences Abstracts KW - elderly KW - exercise KW - intervention KW - lifestyle KW - nap KW - nodding KW - sleep KW - Gerontology KW - Exercise KW - Sleep and wakefulness KW - Maintenance KW - Physical training KW - Mental disorders KW - Efficiency KW - Sleep KW - Geriatrics KW - Mental health KW - Psychiatry KW - N3 11001:Behavioral and Cognitive Neuroscience KW - PE 120:Sport: Psychology, Sociology & History UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20466990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+and+Clinical+Neurosciences&rft.atitle=Effects+of+short+nap+and+exercise+on+elderly+people+having+difficulty+in+sleeping&rft.au=Tanaka%2C+Hideki%3BTaira%2C+Kazuhiko%3BArakawa%2C+Masashi%3BToguti%2C+Hiroki%3BUrasaki%2C+Chisae%3BYamamoto%2C+Yukari%3BUezu%2C+Eiko%3BHori%2C+Tadao%3BShirakawa%2C+Shuichiro&rft.aulast=Tanaka&rft.aufirst=Hideki&rft.date=2001-06-01&rft.volume=55&rft.issue=3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Psychiatry+and+Clinical+Neurosciences&rft.issn=13231316&rft_id=info:doi/10.1046%2Fj.1440-1819.2001.00813.x LA - English DB - Physical Education Index N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Efficiency; Sleep; Gerontology; Mental health; Exercise; Psychiatry; Maintenance; Mental disorders; Geriatrics; Sleep and wakefulness; Physical training DO - http://dx.doi.org/10.1046/j.1440-1819.2001.00813.x ER - TY - JOUR T1 - Stress-Related Gene Expression in Mice Treated with Inorganic Arsenicals AN - 18813591; 5700259 AB - Arsenic (As) is an environmental chemical of high concern for human health. Acute toxicity of arsenic is dependent on its chemical forms and proximity to high local arsenic concentrations is one of the mechanisms for cell death. This study was designed to define acute arsenic-induced stress-related gene expression in vivo. Mice were injected sc with either sodium arsenite [As(III), 100 mu mol/kg], sodium arsenate [As(V), 300 mu mol/kg], or saline. To examine stress-related gene expression, livers were removed 3 h after arsenic injection for RNA and protein extraction. The Atlas Mouse Stress/Toxicology array revealed that the expression of genes related to stress, DNA damage, and metabolism was altered by acute arsenic treatments. Expression of heme oxygenase 1 (HO-1), a hallmark for arsenic-induced stress, was increased 10-fold, along with increases in heat shock protein-60 (HSP60), DNA damage inducible protein GADD45, and the DNA excision repair protein ERCC1. Downregulation of certain cytochrome P450 enzymes occurred with arsenic treatment. Multiprobe RNase protection assay revealed the activation of the c-Jun/AP-1 transcription complex after arsenic treatments. Western blot analysis further confirmed the enhanced production of arsenic-induced stress proteins such as HO-1, HSP70, HSP90, metallothionein, the metal-responsive transcription factor MTF-1, nuclear factor kappa B and c-Jun/AP-1. Increases in caspase-1 and cytokines such as tumor necrosis factor- alpha (TNF- alpha ) and macrophage inflammatory protein-2 were also evident. In summary, this study profiled the gene expression pattern in mice treated with inorganic arsenicals, which adds to our understanding of acute arsenic poisoning and toxicity. JF - Toxicological Sciences AU - Liu, Jie AU - Kadiiska, M B AU - Liu, Yaping AU - Lu, Tong AU - Qu, Wei AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute for Environmental Health Sciences, Mail Drop F0-09, Research Triangle Park, NC 27709, USA Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 314 EP - 320 VL - 61 IS - 2 SN - 1096-6080, 1096-6080 KW - Gadd45 protein KW - Hsp60 protein KW - heme oxygenase-1 KW - mice KW - sodium arsenate KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18813591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Stress-Related+Gene+Expression+in+Mice+Treated+with+Inorganic+Arsenicals&rft.au=Liu%2C+Jie%3BKadiiska%2C+M+B%3BLiu%2C+Yaping%3BLu%2C+Tong%3BQu%2C+Wei%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2001-06-01&rft.volume=61&rft.issue=2&rft.spage=314&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Statistical Issues in the Analysis of Low-Dose Endocrine Disruptor Data AN - 18812135; 5700247 AB - The National Institute of Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (U.S. EPA) recently cosponsored the Endocrine Disruptors Low-Dose Peer Review. The purpose of this meeting was to examine data supporting the presence or absence of low-dose effects of endocrine disruptors in specific studies and then to evaluate the likelihood and significance of these and/or other potential low-dose effects for humans. All invited speakers agreed to provide their raw data in advance of the meeting to a Statistics Subpanel, which was asked to reevaluate the authors' experimental design, data analysis, and interpretation of experimental results. The purpose of this statistical reevaluation was to provide an independent assessment of the experimental design and data analysis used in each of the studies and to identify key statistical issues relevant to the evaluation and interpretation of the data. This paper presents a summary of the Statistics Subpanel's evaluation. Specific examples are presented to illustrate problems that arose in the experimental design and data analysis of certain studies. The statistical principles and issues that are discussed in this paper are not unique to endocrine disruptor studies and should provide important guidelines regarding appropriate experimental design and statistical analysis for other types of laboratory investigations. JF - Toxicological Sciences AU - Haseman, J K AU - Bailer, A J AU - Kodell, R L AU - Morris, R AU - Portier, K AD - Biostatistics Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 201 EP - 210 VL - 61 IS - 2 SN - 1096-6080, 1096-6080 KW - endocrine disruptors KW - Toxicology Abstracts KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18812135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Statistical+Issues+in+the+Analysis+of+Low-Dose+Endocrine+Disruptor+Data&rft.au=Haseman%2C+J+K%3BBailer%2C+A+J%3BKodell%2C+R+L%3BMorris%2C+R%3BPortier%2C+K&rft.aulast=Haseman&rft.aufirst=J&rft.date=2001-06-01&rft.volume=61&rft.issue=2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study AN - 18642332; 5538868 AB - Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degree /s in 2,627 men and women aged 70-79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 plus or minus 34.5 vs. 81.4 plus or minus 22.0 N times m, P < 0.01). Men had greater muscle attenuation values (37.3 plus or minus 6.5 vs. 34.7 plus or minus 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 plus or minus 22.4 vs. 93.3 plus or minus 17.5 cm super(2), P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 plus or minus 0.21 vs. 0.88 plus or minus 0.21 N times m times cm- super(2)). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 plus or minus 8.7 vs. 41.1 plus or minus 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest (P < 0.01) in the eldest men and women and were negatively associated with total body fat (r = _0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production (r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity. JF - Journal of Applied Physiology AU - Goodpaster, B H AU - Carlson, CL AU - Visser, M AU - Kelley, DE AU - Scherzinger, A AU - Harris, T B AU - Stamm, E AU - Newman, AB AD - Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; National Institute on Aging, Bethesda, Maryland 20892, USA Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 2157 EP - 2165 VL - 90 IS - 6 SN - 8750-7587, 8750-7587 KW - Physical Education Index KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18642332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Physiology&rft.atitle=Attenuation+of+skeletal+muscle+and+strength+in+the+elderly%3A+The+Health+ABC+Study&rft.au=Goodpaster%2C+B+H%3BCarlson%2C+CL%3BVisser%2C+M%3BKelley%2C+DE%3BScherzinger%2C+A%3BHarris%2C+T+B%3BStamm%2C+E%3BNewman%2C+AB&rft.aulast=Goodpaster&rft.aufirst=B&rft.date=2001-06-01&rft.volume=90&rft.issue=6&rft.spage=2157&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Physiology&rft.issn=87507587&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Radiation safety training for nuclear cardiologists AN - 18501858; 5475095 AB - Employees in the Nuclear Medicine and Positron Emission Tomography (PET) Departments require radiation safety training in order to safely perform their duties involving the use of radioactive material in humans. In the sub-field of Nuclear Cardiology, hospitals and clinics often order unit doses of radiopharmaceuticals, thus minimizing the need for full-time Radiopharmacy and Health Physics support staff. super(Tc-99)m labeled compounds such as sodium pertechnetate and sestamibi, and super(201)T1 in the form thallium chloride are widely used for gated blood pool and heart stress studies. PET radiopharmaceuticals such as super(13)N labeled ammonia and super(18)F labeled fluorodeoxyglucose (FDG) are used for perfusion and metabolism studies. The lack of on-site radiopharmaceutical preparation does not negate the need for radiation safety training, especially for physicians, technicians, and nurses who often have other obligations when dealing with patients. Training course materials prepared for nuclear cardiologists covered the following topics: basic radiation science; radiation dose profiles for the radiopharmaceuticals used; bioeffects of radiation; the ALARA concept and safety procedures; and emergency response. JF - Health Physics AU - Ribaudo, CA AD - National Institutes of Health, Building 21, 21 Wilson Drive, MSC-6780, Bethesda, MD 20892-6780, USA Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 1 PB - Williams & Wilkins, 351 W. Camden St. Baltimore MD 21201 USA VL - 80 IS - 6 SN - 0017-9078, 0017-9078 KW - Risk Abstracts; Health & Safety Science Abstracts KW - H 8000:Radiation Safety/Electrical Safety KW - R2 23020:Technological risks KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18501858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=Radiation+safety+training+for+nuclear+cardiologists&rft.au=Ribaudo%2C+CA&rft.aulast=Ribaudo&rft.aufirst=CA&rft.date=2001-06-01&rft.volume=80&rft.issue=6&rft.spage=S134&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Novel chemistry of abdominal defensive glands of nymphalid butterfly Agraulis vanillae AN - 18202480; 5238262 AB - Abdominal defensive glands of both sexes of the Gulf fritillary butterfly, Agraulis vanillae (Linnaeus) (Nymphalidae:Heliconiinae) emit a pronounced odor when disturbed. We have identified 6-methyl-5-hepten-2-one; oleic, palmitic, and stearic esters of the corresponding alcohol 6-methyl-5-hepten-2-ol; hexadecyl acetate; 1,16-hexadecanediol diacetate; and 1,15-hexadecanediol diacetate in the glandular exudate. Since we have determined that free-flying birds or birds in a butterfly conservatory discriminate against A. vanillae as prey, we suggest that the constituents in the glands may play a defensive role against potential avian predators. JF - Journal of Chemical Ecology AU - Ross, G N AU - Fales, H M AU - Lloyd, HA AU - Jones, T AU - Sokoloski, E A AU - Marshall-Batty, K AU - Blum AD - Laboratory of Biophysical Chemistry, NHLBI, NIH, Bethesda, Maryland 20892, USA Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 1219 EP - 1228 VL - 27 IS - 6 SN - 0098-0331, 0098-0331 KW - Lepidoptera KW - Brush-footed butterflies KW - Gulf fritillary KW - Ecology Abstracts; Animal Behavior Abstracts; Chemoreception Abstracts; Entomology Abstracts KW - Nymphalidae KW - Anti-predator behavior KW - Glands KW - Defense secretions KW - Agraulis vanillae KW - D 04659:Insects KW - Y 25693:Insects KW - R 18054:Others KW - Z 05179:Glands & secretions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18202480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Chemical+Ecology&rft.atitle=Novel+chemistry+of+abdominal+defensive+glands+of+nymphalid+butterfly+Agraulis+vanillae&rft.au=Ross%2C+G+N%3BFales%2C+H+M%3BLloyd%2C+HA%3BJones%2C+T%3BSokoloski%2C+E+A%3BMarshall-Batty%2C+K%3BBlum&rft.aulast=Ross&rft.aufirst=G&rft.date=2001-06-01&rft.volume=27&rft.issue=6&rft.spage=1219&rft.isbn=&rft.btitle=&rft.title=Journal+of+Chemical+Ecology&rft.issn=00980331&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nymphalidae; Agraulis vanillae; Glands; Defense secretions; Anti-predator behavior ER - TY - JOUR T1 - Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks AN - 18167801; 5144506 AB - The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification. Expression of several of these genes has been reported in SRBCTs, but most have not been associated with these cancers. To test the ability of the trained ANN models to recognize SRBCTs, we analyzed additional blinded samples that were not previously used for the training procedure, and correctly classified them in all cases. This study demonstrates the potential applications of these methods for tumor diagnosis and the identification of candidate targets for therapy. JF - Nature Medicine AU - Khan, J AU - Wei, J S AU - Ringner, M AU - Saal, L H AU - Ladanyi, M AU - Westermann, F AU - Berthold, F AU - Schwab, M AU - Antonescu, C R AU - Peterson, C AU - Meltzer, P S AD - Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA, khanjav@mail.nih.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 673 EP - 679 VL - 7 IS - 6 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene expression KW - Neural networks KW - Cancer KW - W3 33135:Diagnosis: Other KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18167801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Classification+and+diagnostic+prediction+of+cancers+using+gene+expression+profiling+and+artificial+neural+networks&rft.au=Khan%2C+J%3BWei%2C+J+S%3BRingner%2C+M%3BSaal%2C+L+H%3BLadanyi%2C+M%3BWestermann%2C+F%3BBerthold%2C+F%3BSchwab%2C+M%3BAntonescu%2C+C+R%3BPeterson%2C+C%3BMeltzer%2C+P+S&rft.aulast=Khan&rft.aufirst=J&rft.date=2001-06-01&rft.volume=7&rft.issue=6&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Gene expression; Neural networks ER - TY - JOUR T1 - An Improved GC/MS-Based Procedure for the Quantitation of the Isoprostane 15-F sub(2t)-IsoP in Rat Plasma AN - 18151781; 5160971 AB - This article describes a procedure for the quantitation of the isoprostane 15-F sub(2t)-IsoP (9a, 11a, 15S-trihydroxy-(8b)-prosta-5Z,13E-dien-1-oic acid [CAS#27415-26-5] formerly known as 8-epi-PGF sub(2a) or 8-iso-PGF sub(2a), and also as iPF sub(2a)-III). We have combined features from several earlier methods for 15-F sub(2t)-IsoP and prostaglandins, and identified and modified those steps that may lead to poor recoveries. The resulting protocol is precise and reliable, and was validated by a blind time-course study of plasma levels in rats treated with 120 and 1200 mg CCl sub(4)/ kg body weight. Plasma levels of 15-F sub(2t)-IsoP, as measured according to the procedure described above, are good indicators of acute oxidative stress as induced by CCl sub(4). The precision of the measurements allows detection of elevated plasma 15-F sub(2t)-IsoP levels as long as 16 h after an acute exposure of 120 mg CCl sub(4)/kg body weight, and 2 h after an exposure of 1 mg CCl sub(4)/kg body weight. The results of this low-dose, pilot study suggest that this method has sufficient analytical precision to allow the detection of the small changes in plasma isoprostane levels, which result from chronic and/or lower-level exposures to agents causing oxidative stress. JF - Molecular Biotechnology AU - Parker, CE AU - Graham, LRB AU - Nguyen, M-N AU - Gladen, B C AU - Kadiiska, M B AU - Barrett, J C AU - Tomer, K B AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 105 EP - 118 VL - 18 IS - 2 SN - 1073-6085, 1073-6085 KW - rats KW - isoprostane KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Plasma KW - Body weight KW - Oxidative stress KW - Gas chromatography KW - Mass spectroscopy KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18151781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=An+Improved+GC%2FMS-Based+Procedure+for+the+Quantitation+of+the+Isoprostane+15-F+sub%282t%29-IsoP+in+Rat+Plasma&rft.au=Parker%2C+CE%3BGraham%2C+LRB%3BNguyen%2C+M-N%3BGladen%2C+B+C%3BKadiiska%2C+M+B%3BBarrett%2C+J+C%3BTomer%2C+K+B&rft.aulast=Parker&rft.aufirst=CE&rft.date=2001-06-01&rft.volume=18&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mass spectroscopy; Gas chromatography; Plasma; Body weight; Oxidative stress ER - TY - JOUR T1 - Traffic-related air pollution in Calcutta associated with increased respiratory symptoms and impaired alveolar macrophage activity AN - 18116314; 5209286 AB - Lung response to vehicular pollution in Calcutta has been investigated. Respiratory symptoms including cough, sinusitis, bronchitis and asthma were found in about 78% of exposed group in Calcutta (traffic-policemen and street-hawkers) compared to 24% in rural controls. A 6.5-fold rise in the number of alveolar macrophages (AM) was found in sputum of urban group and the AM were highly active with respect to synthesis and release of hydrolytic enzymes, acid phosphatase and elastase. The study group comprises of only nonsmokers, hence the changes were not due to smoking habit. The results indicate that chronic exposure to traffic-related air pollution in Calcutta cause high incidence of respiratory illness and impaired macrophage activity. JF - Journal of Environment and Pollution AU - Basu, C AU - Ray, M R AU - Lahiri, T AD - Department of Neuroendocrinology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta-700 026, India Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 187 EP - 195 VL - 8 IS - 2 SN - 0971-4871, 0971-4871 KW - man KW - Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - Macrophages KW - India, Calcutta KW - Respiration KW - Motor vehicles KW - Pollution effects KW - Urban areas KW - Respiratory tract KW - Asthma KW - Alveoli KW - Air pollution KW - Automotive exhaust emissions KW - X 24240:Miscellaneous KW - H 11000:Diseases/Injuries/Trauma KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18116314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environment+and+Pollution&rft.atitle=Traffic-related+air+pollution+in+Calcutta+associated+with+increased+respiratory+symptoms+and+impaired+alveolar+macrophage+activity&rft.au=Basu%2C+C%3BRay%2C+M+R%3BLahiri%2C+T&rft.aulast=Basu&rft.aufirst=C&rft.date=2001-06-01&rft.volume=8&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environment+and+Pollution&rft.issn=09714871&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - India, Calcutta; Respiratory tract; Automotive exhaust emissions; Pollution effects; Air pollution; Urban areas; Asthma; Motor vehicles; Respiration; Macrophages; Alveoli ER - TY - JOUR T1 - Mouthwash in the etiology of oral cancer in Puerto Rico AN - 18106089; 5201601 AB - To determine if the risk of cancers of the mouth and pharynx is associated with mouthwash use in Puerto Rico, an area of relatively high risk. Interviews were conducted with 342 cases of oral and pharyngeal cancer registered in Puerto Rico and diagnosed between 1992 and 1995 and with 521 population-based controls regarding mouthwash use and other factors. Mouthwash-related risks were estimated using unconditional logistic regression controlling for potential confounders. The adjusted odds ratio associated with using mouthwash with an alcohol content of 25% or greater was 1.0. Risks were not higher with greater frequency, years of use, or lifetime mouthwash exposure. Among tobacco and alcohol abstainers the odds ratio associated with mouthwash use was 2.8 (CI = 0.8-9.9), in contrast to 0.8 (CI = 0.4-1.7) and 0.9 (CI = 0.6-1.3) among those with light and heavy cigarette smoking/alcohol drinking behaviors, respectively. There was no overall increased risk of oral cancer associated with mouthwash use. An elevated, but not statistically significant, risk was observed among the small number of subjects who neither smoked cigarettes nor drank alcohol, among whom an effect of alcohol-containing mouthwash would be most likely evident. Our findings indicate the need to clarify the mechanisms of oral carcinogenesis, including the possible role of alcohol-containing mouthwash. JF - Cancer Causes & Control AU - Winn, D M AU - Diehl AU - Brown, L M AU - Harty, L C AU - Bravo-Otero, E AU - Fraumeni, JF Jr AU - Kleinman, D V AU - Hayes, R B AD - Division of Cancer Control and Population Sciences, 6130 Executive Blvd., Room 5114, MSC 7395, Bethesda, MD 20892-7395, USA, Winnde@mail.nih.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 419 EP - 429 VL - 12 IS - 5 SN - 0957-5243, 0957-5243 KW - man KW - epidemiology KW - Toxicology Abstracts KW - Toiletries KW - Pharynx KW - Puerto Rico KW - Mouthwashes KW - Mouth KW - Oral cavity KW - Cancer KW - X 24140:Cosmetics, toiletries & household products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18106089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Mouthwash+in+the+etiology+of+oral+cancer+in+Puerto+Rico&rft.au=Winn%2C+D+M%3BDiehl%3BBrown%2C+L+M%3BHarty%2C+L+C%3BBravo-Otero%2C+E%3BFraumeni%2C+JF+Jr%3BKleinman%2C+D+V%3BHayes%2C+R+B&rft.aulast=Winn&rft.aufirst=D&rft.date=2001-06-01&rft.volume=12&rft.issue=5&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Puerto Rico; Mouthwashes; Cancer; Mouth; Toiletries; Oral cavity; Pharynx ER - TY - JOUR T1 - A dominant-negative therapy for anthrax AN - 17918537; 5144522 AB - The oligomeric structure of anthrax toxin might be exploited as a preventative or therapeutic vaccine. JF - Nature Medicine AU - Leppla, SH AD - Oral Infection and Immunity Branch, National Institute of Dental & Craniofacial Research, National Institutes of Health, Bethesda, MD, USA, Leppla@nih.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 659 EP - 660 VL - 7 IS - 6 SN - 1078-8956, 1078-8956 KW - anthrax toxin KW - Microbiology Abstracts B: Bacteriology KW - Protein structure KW - Anthrax KW - Vaccines KW - Bacillus anthracis KW - Toxins KW - J 02822:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17918537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=A+dominant-negative+therapy+for+anthrax&rft.au=Leppla%2C+SH&rft.aulast=Leppla&rft.aufirst=SH&rft.date=2001-06-01&rft.volume=7&rft.issue=6&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Anthrax; Toxins; Protein structure; Vaccines ER - TY - JOUR T1 - Microinjection Technique Used to Study Functional Interaction Between p53 and Hepatitis B Virus X Gene in Apoptosis AN - 17916445; 5160976 AB - Microinjection of expression vectors into cultured cells has been utilized to study functional interaction of p53 and the hepatitis B virus HBx gene in apoptosis. This approach allows us to determine protein-protein interactions in primary cultured human cells at a single cell level, including fibroblasts, mammary epithelial cells, renal epithelial cells, and hepatocytes. In principle, this approach can be used to study functional interaction of p53 and any gene that is either pro- or anti-apoptotic. The use of primary cultured human cells minimizes ambiguous results associated with immortalized or tumorigenic cell lines. Moreover, it is an easy and effective way to `igintroduce genes of interests into primary human cells with defined genetic ndefects, thereby facilitating the delineation of genetic pathways. JF - Molecular Biotechnology AU - Wang, X W AD - Liver Carcinogenesis Section; Lab. Human Carcinogenesis, National Cancer Institute, NIH, Bldg. 37, Room 2025, 37 Convent Drive, Bethesda, MD 20892-4255, USA, xin_wei_wang@nih.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 169 EP - 177 VL - 18 IS - 2 SN - 1073-6085, 1073-6085 KW - Hepatitis B virus KW - double prime X gene KW - p53 protein KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - X gene KW - ^AX gene KW - Expression vectors KW - Apoptosis KW - Cell culture KW - Microinjection KW - V 22050:Viral genetics including virus reactivation KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17916445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=Microinjection+Technique+Used+to+Study+Functional+Interaction+Between+p53+and+Hepatitis+B+Virus+X+Gene+in+Apoptosis&rft.au=Wang%2C+X+W&rft.aulast=Wang&rft.aufirst=X&rft.date=2001-06-01&rft.volume=18&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis B virus; Expression vectors; Apoptosis; Microinjection; Cell culture ER - TY - JOUR T1 - Hydrocarbon Carcinogens Evade Cellular Defense Mechanism of G1 Arrest in Nontransformed and Malignant Lung Cell Lines AN - 17898885; 5131805 AB - In previous studies using human breast carcinoma cells (MCF-7) and human colon carcinoma cells (RKO) we have shown that, in response to treatment with hydrocarbon carcinogens, these cell lines failed to undergo a p53-mediated cell cycle arrest in G1 phase; rather, the cells were accumulated in the S phase with damaged DNA, a situation that may lead to replication of DNA on a damaged template, resulting in the enhanced frequency of mutations in the daughter cells. This has been termed a stealth effect. In the present work we have demonstrated that the stealth effect also pertains for lung cells. In E10 nontransformed mouse lung type II cells, two potent hydrocarbon carcinogens, benzo[a]pyrene dihydrodiol epoxide and benzo[g]chrysene dihydrodiol epoxide, damaged DNA as suggested by retardation in S phase, but did not cause G1 arrest, in contrast to the positive control, actinomycin D. Human lung adenocarcinoma A549 cells, with normal p53, likewise exhibited G1 arrest after actinomycin D, but not after treatment with the diol epoxides. Several human lung cancer cell lines with absent or mutant p53, such as H358, H1734, and H82, exhibited no G1 arrest after any of the compounds. However, lung H441 adenocarcinoma cells, with a mutation in exon 5, codon 158 of p53, exhibited partial G1 arrest after the diol epoxides as well as actinomycin D, and H2030 adenocarcinoma cells did not show G1 arrest after any of the chemicals despite a normal p53. The stealth effect of evasion of G1 arrest may contribute to initiation of lung adenocarcinomas and to progression of tumors. A role in resistance to chemotherapy by certain drugs is also likely. JF - Toxicology and Applied Pharmacology AU - Khan, Q A AU - Anderson, L M AD - Cellular Pathogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland, 21702, khanq@mail.nih.gov Y1 - 2001/06/01/ PY - 2001 DA - 2001 Jun 01 SP - 105 EP - 113 PB - Academic Press VL - 173 IS - 2 SN - 0041-008X, 0041-008X KW - G1 phase KW - cell lines KW - Toxicology Abstracts KW - Polycyclic aromatic hydrocarbons KW - Lung KW - Hydrocarbons KW - Tumorigenesis KW - Cell cycle KW - Carcinogens KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17898885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Hydrocarbon+Carcinogens+Evade+Cellular+Defense+Mechanism+of+G1+Arrest+in+Nontransformed+and+Malignant+Lung+Cell+Lines&rft.au=Khan%2C+Q+A%3BAnderson%2C+L+M&rft.aulast=Khan&rft.aufirst=Q&rft.date=2001-06-01&rft.volume=173&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2001.9172 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hydrocarbons; Lung; Carcinogens; Cell cycle; Polycyclic aromatic hydrocarbons; Tumorigenesis DO - http://dx.doi.org/10.1006/taap.2001.9172 ER - TY - JOUR T1 - Adaptation of Chimeric Retroviruses In Vitro and In Vivo: Isolation of Avian Retroviral Vectors with Extended Host Range AN - 17856266; 5107460 AB - We have designed and characterized two new replication-competent avian sarcoma/leukosis virus-based retroviral vectors with amphotropic and ecotropic host ranges. The amphotropic vector RCASBP-M2C(797-8), was obtained by passaging the chimeric retroviral vector RCASBP-M2C(4070A) (6) in chicken embryos. The ecotropic vector, RCASBP(Eco), was created by replacing the env-coding region in the retroviral vector RCASBP(A) with the env region from an ecotropic murine leukemia virus. It replicates efficiently in avian DFJ8 cells that express murine ecotropic receptor. For both vectors, permanent cell lines that produce viral stocks with titers of about 5 x 10 CFU/ml on mammalian cells can be easily established by passaging transfected avian cells. Some chimeric viruses, for example, RCASBP(Eco), replicate efficiently without modifications. For those chimeric viruses that do require modification, adaptation by passage in vitro or in vivo is a general strategy. This strategy has been used to prepare vectors with altered host range and could potentially be used to develop vectors that would be useful for targeted gene delivery. JF - Journal of Virology AU - Barsov, E V AU - Payne, W S AU - Hughes, SH AD - HIV Drug Resistance Program, NCI-Frederick, P.O. Box B, Building 539, Room 130A, Frederick, MD 21702-1201, hughes@ncifcrf.gov Y1 - 2001/06// PY - 2001 DA - Jun 2001 SP - 4973 EP - 4983 VL - 75 IS - 11 SN - 0022-538X, 0022-538X KW - chick embryos KW - gene delivery KW - Avian leukosis virus KW - Avian sarcoma virus KW - Murine leukemia virus KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Host range KW - Vectors KW - Expression vectors KW - Retrovirus KW - Chimerism KW - N 14682:Cloning vectors KW - W3 33181:Gene therapy vectors KW - V 22023:Virus behavior in cell culture KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17856266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Adaptation+of+Chimeric+Retroviruses+In+Vitro+and+In+Vivo%3A+Isolation+of+Avian+Retroviral+Vectors+with+Extended+Host+Range&rft.au=Barsov%2C+E+V%3BPayne%2C+W+S%3BHughes%2C+SH&rft.aulast=Barsov&rft.aufirst=E&rft.date=2001-06-01&rft.volume=75&rft.issue=11&rft.spage=4973&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.75.11.4973-4983.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Murine leukemia virus; Avian leukosis virus; Avian sarcoma virus; Retrovirus; Host range; Expression vectors; Vectors; Chimerism DO - http://dx.doi.org/10.1128/JVI.75.11.4973-4983.2001 ER - TY - JOUR T1 - The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma. AN - 70958817; 11423971 AB - Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol. JF - Oncogene AU - Leone, A AU - Mitsiades, N AU - Ward, Y AU - Spinelli, B AU - Poulaki, V AU - Tsokos, M AU - Kelly, K AD - Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Room 3B43, 9000, Rockville Pike, Bethesda, Maryland, MD 20892, USA. Y1 - 2001/05/31/ PY - 2001 DA - 2001 May 31 SP - 3217 EP - 3225 VL - 20 IS - 25 SN - 0950-9232, 0950-9232 KW - Cholinergic Agonists KW - 0 KW - Immediate-Early Proteins KW - Neoplasm Proteins KW - Receptors, Muscarinic KW - Carbachol KW - 8Y164V895Y KW - GEM protein, human KW - EC 3.6.5.2 KW - Gem protein, mouse KW - Monomeric GTP-Binding Proteins KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Trigeminal Ganglion -- chemistry KW - Animals KW - Melanoma -- pathology KW - Tumor Cells, Cultured KW - Humans KW - Cholinergic Agonists -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation KW - Mice KW - Carbachol -- pharmacology KW - Receptors, Muscarinic -- metabolism KW - Neuroblastoma -- pathology KW - Ganglioneuroblastoma -- pathology KW - Immediate-Early Proteins -- genetics KW - Immediate-Early Proteins -- metabolism KW - Monomeric GTP-Binding Proteins -- metabolism KW - Neoplasm Proteins -- metabolism KW - Monomeric GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70958817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+Gem+GTP-binding+protein+promotes+morphological+differentiation+in+neuroblastoma.&rft.au=Leone%2C+A%3BMitsiades%2C+N%3BWard%2C+Y%3BSpinelli%2C+B%3BPoulaki%2C+V%3BTsokos%2C+M%3BKelly%2C+K&rft.aulast=Leone&rft.aufirst=A&rft.date=2001-05-31&rft.volume=20&rft.issue=25&rft.spage=3217&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagens that are not carcinogens: faulty theory or faulty tests? AN - 70906137; 11377241 AB - In the National Toxicology Program database of 172 chemicals that were judged non-carcinogenic or equivocal in 2 year rodent studies in both sexes of rats and mice, there are 38 chemicals that were mutagenic in Salmonella. All but two of the chemicals had structural alerts for mutagenicity. The largest proportion of the mutagenic non-carcinogens were benzeneamines and substituted benzeneamines. In all, 12 of the mutagenic non-carcinogens had mutagenic carcinogen analogues, and for two chemicals, the carcinogenic analogues were not mutagenic. Non-carcinogens that were mutagenic in Salmonella also tended to be mutagenic and clastogenic in mammalian in vitro tests. The mutagenic responses are discussed and explanations offered for the mutagenicity and lack of carcinogenic activity of these chemicals. JF - Mutation research AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. zeiger@nc.rr.com Y1 - 2001/05/31/ PY - 2001 DA - 2001 May 31 SP - 29 EP - 38 VL - 492 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Mutagens KW - Xenobiotics KW - Index Medicus KW - Animals KW - Reproducibility of Results KW - Mice KW - Salmonella typhimurium -- drug effects KW - Structure-Activity Relationship KW - False Positive Reactions KW - Rats KW - Mutagenicity Tests KW - Carcinogenicity Tests KW - Databases, Factual KW - Salmonella typhimurium -- genetics KW - Female KW - Male KW - Mutagens -- classification KW - Carcinogens -- classification KW - Xenobiotics -- classification KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Xenobiotics -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70906137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mutagens+that+are+not+carcinogens%3A+faulty+theory+or+faulty+tests%3F&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=2001-05-31&rft.volume=492&rft.issue=1-2&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-05-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Mutat Res 2001 Nov 15;498(1-2):219 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical and oral administration of the natural water-soluble antioxidant from spinach reduces the multiplicity of papillomas in the Tg.AC mouse model AN - 17928556; 5160078 AB - The Tg.AC mouse carrying the v-Ha-ras structural gene is a useful model for the study of chemical carcinogens, especially those acting via non-genotoxic mechanisms. This study evaluated the efficacy of the non-toxic, water-soluble antioxidant from spinach, natural antioxidant (NAO), in reducing skin papilloma induction in female hemizygous Tg.AC mice treated dermally five times over 2.5 weeks with 2.5 mu g 12-O-tetradecanoylphorbol-13-acetate (TPA). The TPA-only group was considered as a control; the other two groups received, additionally, NAO topically (2 mg) or orally (100 mg/kg), 5 days/week for 5 weeks. Papilloma counts made macroscopically during the clinical observations showed a significant decrease in multiplicity (P < 0.01) in the NAO topically treated group. According to histological criteria, papilloma multiplicity were lower in both topical-NAO and oral-NAO groups, but significantly so only in the oral-NAO mice (P < 0.01). The beneficial effect of NAO in the Tg.AC mouse is reported. JF - Toxicology Letters AU - Nyska, A AU - Lomnitski, L AU - Spalding, J AU - Dunson, D B AU - Goldsworthy, T L AU - Grossman, S AU - Bergman, M AU - Boorman, G AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, USA, nyska@niehs.nih.gov Y1 - 2001/05/31/ PY - 2001 DA - 2001 May 31 SP - 33 EP - 44 VL - 122 IS - 1 SN - 0378-4274, 0378-4274 KW - topical administration KW - mice KW - v-Ha-ras gene KW - Toxicology Abstracts KW - Phorbol esters KW - Antioxidants KW - Animal models KW - Oral administration KW - Papilloma KW - X 24172:Plants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17928556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Topical+and+oral+administration+of+the+natural+water-soluble+antioxidant+from+spinach+reduces+the+multiplicity+of+papillomas+in+the+Tg.AC+mouse+model&rft.au=Nyska%2C+A%3BLomnitski%2C+L%3BSpalding%2C+J%3BDunson%2C+D+B%3BGoldsworthy%2C+T+L%3BGrossman%2C+S%3BBergman%2C+M%3BBoorman%2C+G&rft.aulast=Nyska&rft.aufirst=A&rft.date=2001-05-31&rft.volume=122&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Oral administration; Antioxidants; Animal models; Papilloma; Phorbol esters ER - TY - JOUR T1 - Linking toxicology and epidemiology: the role of mechanistic modelling AN - 17879469; 5126748 AB - Much of modern environmental science concentrates on protecting people from potentially harmful chemicals such as pesticides and herbicides. Safeguarding humans from unhealthy exposures usually includes two problematic steps. First, even though humans experience low-level exposures to many compounds, human risk must be determined from toxicological experiments or occupational observations that generally have much higher exposures. Second, scientists usually must extrapolate from a chemical's effect in rodents - the traditional experimental models - to humans. The National Institute of Environmental Health Sciences' (NIEHS) Laboratory of Computational Biology and Risk Analysis (CoBRA) is working to solve the problems associated with these steps by designing biologically-based mechanistic models (BBMM) to guide the interpretation of the available data. The resulting knowledge can be applied to predict risks, for example, predicting a particular compound's carcinogenic potential. The eventual goal of this effort is to quantitatively link the likelihood of a disease to environmental causes. JF - Statistics in Medicine AU - Portier, C J AD - Division of Intramural Research, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, NC 27709-2233, USA, portier@niehs.nih.gov Y1 - 2001/05/30/ PY - 2001 DA - 2001 May 30 SP - 1387 EP - 1393 VL - 20 IS - 9-10 SN - 0277-6715, 0277-6715 KW - Toxicology Abstracts KW - Risk assessment KW - Epidemiology KW - Extrapolation KW - Pesticides KW - Animal models KW - Herbicides KW - Diseases KW - Carcinogens KW - Environmental factors KW - Toxicology KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17879469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+Medicine&rft.atitle=Linking+toxicology+and+epidemiology%3A+the+role+of+mechanistic+modelling&rft.au=Portier%2C+C+J&rft.aulast=Portier&rft.aufirst=C&rft.date=2001-05-30&rft.volume=20&rft.issue=9-10&rft.spage=1387&rft.isbn=&rft.btitle=&rft.title=Statistics+in+Medicine&rft.issn=02776715&rft_id=info:doi/10.1002%2Fsim.676 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Animal models; Toxicology; Epidemiology; Extrapolation; Pesticides; Herbicides; Risk assessment; Carcinogens; Environmental factors; Diseases DO - http://dx.doi.org/10.1002/sim.676 ER - TY - JOUR T1 - Targeting of Tumor Cells by Cell Surface Urokinase Plasminogen Activator-dependent Anthrax Toxin AN - 17869112; 5114676 AB - Urokinase plasminogen activator receptor (uPAR) binds pro-urokinase plasminogen activator (pro-uPA) and thereby localizes it near plasminogen, causing the generation of active uPA and plasmin on the cell surface. uPAR and uPA are overexpressed in a variety of human tumors and tumor cell lines, and expression of uPAR and uPA is highly correlated to tumor invasion and metastasis. To exploit these characteristics in the design of tumor cell-selective cytotoxins, we constructed mutated anthrax toxin-protective antigen (PrAg) proteins in which the furin cleavage site is replaced by sequences cleaved specifically by uPA. These uPA-targeted PrAg proteins were activated selectively on the surface of uPAR-expressing tumor cells in the presence of pro-uPA and plasminogen. The activated PrAg proteins caused internalization of a recombinant cytotoxin, FP59, consisting of anthrax toxin lethal factor residues 1-254 fused to the ADP-ribosylation domain of Pseudomonas exotoxin A, thereby killing the uPAR-expressing tumor cells. The activation and cytotoxicity of these uPA-targeted PrAg proteins were strictly dependent on the integrity of the tumor cell surface-associated plasminogen activation system. We also constructed a mutated PrAg protein that selectively killed tissue plasminogen activator-expressing cells. These mutated PrAg proteins may be useful as new therapeutic agents for cancer treatment. JF - Journal of Biological Chemistry AU - Liu, S AU - Bugge, TH AU - Leppla, SH AD - Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2001/05/25/ PY - 2001 DA - 2001 May 25 SP - 17976 EP - 17984 VL - 276 IS - 21 SN - 0021-9258, 0021-9258 KW - targeting KW - anthrax toxin KW - u-plasminogen activator receptors KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Medical and Pharmaceutical Biotechnology Abstracts KW - Anthrax lethal toxin KW - Chemotherapy KW - u-Plasminogen activator KW - Bacillus anthracis KW - Tumor cells KW - Antitumor agents KW - Toxins KW - W3 33374:Antitumor agents KW - W 30965:Miscellaneous, Reviews KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17869112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Targeting+of+Tumor+Cells+by+Cell+Surface+Urokinase+Plasminogen+Activator-dependent+Anthrax+Toxin&rft.au=Liu%2C+S%3BBugge%2C+TH%3BLeppla%2C+SH&rft.aulast=Liu&rft.aufirst=S&rft.date=2001-05-25&rft.volume=276&rft.issue=21&rft.spage=17976&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Chemotherapy; Antitumor agents; Toxins; u-Plasminogen activator; Tumor cells; Anthrax lethal toxin ER - TY - JOUR T1 - Solution structure of a trans-opened (10S)-dA adduct of (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a fully complementary DNA duplex: evidence for a major syn conformation. AN - 70876007; 11352722 AB - Two-dimensional NMR was used to determine the solution structure of an undecanucleotide duplex, d(CGGTCACGAGG).d(CCTCGTGACCG), in which (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene is covalently bonded to the exocyclic N(6)() amino group of the central deoxyadenosine, dA(6), through trans addition at C10 of the epoxide (to give a 10S adduct). The present study represents the first NMR structure of a benzo[a]pyrene (10S)-dA adduct in DNA with a complementary T opposite the modified dA. Exchangeable and nonexchangeable protons of the modified duplex were assigned by the use of TOCSY (in D(2)O) and NOESY spectra (in H(2)O and D(2)O). Sequential NOEs expected for a B-type DNA conformation with typical Watson-Crick base pairing are observed along the duplex, except at the lesion site. We observed a strong intraresidue NOE cross-peak between H1' and H8 of the modified dA(6). The sugar H2' and H2' ' of dC(5) lacked NOE cross-peaks with H8 of dA(6) but showed weak interactions with H2 of dA(6) instead. In addition, the chemical shift of the H8 proton (7.51 ppm) of dA(6) appears at a higher field than that of H2 (8.48 ppm). These NOE and chemical shift data for the dA(6) base protons are typical of a syn glycosidic bond at the modified base. Restrained molecular dynamics/energy minimization calculations show that the hydrocarbon is intercalated from the major groove on the 3'-side of the modified base between base pairs A(6)-T(17) and C(7)-G(16) and confirm the syn glycosidic angle (58 degrees ) of the modified dA(6). In the syn structure, a weak A-T hydrogen bond is possible between the N3-H proton of T(17) and N7 of dA(6) (at a distance of 3.11 A), whereas N1, the usual hydrogen bonding partner for N3-H of T when dA is in the anti conformation, is 6.31 A away from this proton. The 10(S)-dA modified DNA duplex remains in a right-handed helix, which bends in the direction of the aliphatic ring of BaP at about 42 degrees from the helical axis. ROESY experiments provided evidence for interconversion between the major, syn conformer and a minor, possibly anti, conformer. JF - Biochemistry AU - Pradhan, P AU - Tirumala, S AU - Liu, X AU - Sayer, J M AU - Jerina, D M AU - Yeh, H J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/05/22/ PY - 2001 DA - 2001 May 22 SP - 5870 EP - 5881 VL - 40 IS - 20 SN - 0006-2960, 0006-2960 KW - 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene-DNA adduct KW - 0 KW - DNA Adducts KW - Deoxyadenosines KW - Hydrocarbons KW - Nucleic Acid Heteroduplexes KW - Oligonucleotides KW - Protons KW - Solutions KW - Benzo(a)pyrene KW - 3417WMA06D KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Hydrocarbons -- chemistry KW - Stereoisomerism KW - Thermodynamics KW - Nuclear Magnetic Resonance, Biomolecular KW - Spectrophotometry, Ultraviolet KW - Benzo(a)pyrene -- chemistry KW - Molecular Conformation KW - Oligonucleotides -- chemical synthesis KW - DNA Adducts -- chemistry KW - Nucleic Acid Heteroduplexes -- chemistry KW - DNA -- chemistry KW - Deoxyadenosines -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70876007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Solution+structure+of+a+trans-opened+%2810S%29-dA+adduct+of+%28%2B%29-%287S%2C8R%2C9S%2C10R%29-7%2C8-dihydroxy-9%2C10-epoxy-7%2C8%2C9%2C10-tetrahydrobenzo%5Ba%5Dpyrene+in+a+fully+complementary+DNA+duplex%3A+evidence+for+a+major+syn+conformation.&rft.au=Pradhan%2C+P%3BTirumala%2C+S%3BLiu%2C+X%3BSayer%2C+J+M%3BJerina%2C+D+M%3BYeh%2C+H+J&rft.aulast=Pradhan&rft.aufirst=P&rft.date=2001-05-22&rft.volume=40&rft.issue=20&rft.spage=5870&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phospho-Azatyrosine, a less effective protein-tyrosine phosphatase substrate than phosphotyrosine. AN - 70905365; 11392533 AB - Azatyrosine (AzaTyr, 4) is a natural product isolated from Streptomyces chibanesis, whose structure is characterized by a nitrogen atom in the aryl ring of a tyrosyl residue. This seemingly minor modification to the tyrosyl residue results in profound physiological effects, as AzaTyr has been shown to promote permanent reversion of ras-dependent transformed cells to the normal phenotype in culture and to inhibit chemical induction of carcinogenesis in transgenic mice bearing oncogenic human ras. The mechanisms underlying these effects are not known, however ras-pathways involve an intricate balance between both protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). The present study was undertaken to examine the general utility of AzaTyr as a structural motif for PTP inhibitor design by examining the phospho-azatyrosine (pAzaTyr)-containing peptide Ac-Asp-Ala-Asp-Glu-pAzaTyr-Leu-amide (8) in a PTP1 enzyme system. Kinetic analysis indicated that 8 binds with a Km value of 210 microM and a catalytic turnover rate, kcat of 52 s(-1). This represents a greater than 50-fold reduction in binding affinity relative to the parent phosphotyrosine-containing peptide, indicating that the aryl nitrogen adversely affects binding affinity. The much lower PTP affinity of the pAzaTyr-containing peptide reduces the potential utility of the AzaTyr pharmacophore for PTP inhibitor design. These results are discussed from the point of view that incorporation of AzaTyr residues into proteins could result in perturbation of protein-tyrosine phosphorylation,dephosphorylation cascades that control signal transduction processes, including ras-dependent pathways. JF - Bioorganic & medicinal chemistry letters AU - Burke, T R AU - Yao, Z J AU - Ye, B AU - Miyoshi, K AU - Otaka, A AU - Wu, L AU - Zhang, Z Y AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, NCI-FCRDC, Frederick, MD 21702-1201, USA. tburke@helix.nih.gov Y1 - 2001/05/21/ PY - 2001 DA - 2001 May 21 SP - 1265 EP - 1268 VL - 11 IS - 10 SN - 0960-894X, 0960-894X KW - Anticarcinogenic Agents KW - 0 KW - Enzyme Inhibitors KW - Peptides KW - beta-(5-hydroxy-2-pyridyl)alanine KW - 0XTS2H0JH1 KW - Phosphotyrosine KW - 21820-51-9 KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Kinetics KW - Humans KW - Catalytic Domain -- genetics KW - Peptides -- chemistry KW - Molecular Mimicry KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- chemical synthesis KW - Substrate Specificity KW - Drug Design KW - Structure-Activity Relationship KW - Phosphotyrosine -- analogs & derivatives KW - Alanine -- chemical synthesis KW - Alanine -- analogs & derivatives KW - Anticarcinogenic Agents -- chemical synthesis KW - Anticarcinogenic Agents -- pharmacology KW - Phosphotyrosine -- pharmacology KW - Protein Tyrosine Phosphatases -- antagonists & inhibitors KW - Alanine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70905365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Phospho-Azatyrosine%2C+a+less+effective+protein-tyrosine+phosphatase+substrate+than+phosphotyrosine.&rft.au=Burke%2C+T+R%3BYao%2C+Z+J%3BYe%2C+B%3BMiyoshi%2C+K%3BOtaka%2C+A%3BWu%2C+L%3BZhang%2C+Z+Y&rft.aulast=Burke&rft.aufirst=T&rft.date=2001-05-21&rft.volume=11&rft.issue=10&rft.spage=1265&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-30 N1 - Date created - 2001-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiological modeling of a proposed mechanism of enzyme induction by TCDD AN - 17900747; 5141437 AB - A physiological model was previously constructed to facilitate extrapolation of surrogates for the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver to doses comparable to human environmental exposures. The model included induction of P450 isozymes and suggested the presence of multiple binding sites with different affinities for the TCDD-liganded Ah receptor at CYP1A1 dioxin responsive elements. The model also indicated that protein synthesis on the mRNA template exhibited saturation kinetics with respect to message levels. In the present work the earlier model was revised to include the increased proteolysis of the Ah receptor on binding TCDD, more realistic representations of gene transcription and mRNA translation, and different stability for each mRNA. The revised model includes multiple TCDD-liganded Ah receptor binding sites for CYP1A1 and CYP1B1 genes, a lag of 0.2 day for production of mRNA and induced proteins, and stabilization of mRNA by a poly(A) tail. The model reproduced the transient depletion of the Ah receptor subsequent to binding ligand and the dose-response of the receptor in rats treated with biweekly oral doses of TCDD in corn oil. The model reproduced tissue TCDD concentrations observed for several dosing scenarios. Such robustness indicates the utility of the model in estimating internal dose. The model also reproduced the observed dose-response patterns for mRNA and protein for CYP1A1, CYP1A2, and CYP1B1 after repeated dosing. Neither of the two dissociation constants for the Ah receptor bound to the CYP1B1 gene is negligible, supporting the assumption of multiple response elements for this gene. The poorer induction of CYP1B1 was predicted to be due to lower affinity of the dioxin responsive elements for binding the liganded Ah receptor, suggesting the involvement of other regulatory factors, and a shorter poly(A) tail on CYP1B1 mRNA, leading to a shorter lifetime. Saturation in the kinetics of protein synthesis was linked to the limited number of ribosomes that could bind to each message molecule, resulting in fewer ribosomes bound per message at higher doses. Predicted induction at low doses was found to vary widely with the assumptions used in the construction of a model. More detailed descriptions of biological processes might provide more reliable predictions of enzyme induction. JF - Toxicology AU - Kohn, M C AU - Walker, N J AU - Kim, AH AU - Portier, C J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, kohn@valiant.niehs.nih.gov Y1 - 2001/05/21/ PY - 2001 DA - 2001 May 21 SP - 193 EP - 208 VL - 162 IS - 3 SN - 0300-483X, 0300-483X KW - CYP1A1 protein KW - CYP1A2 protein KW - CYP1B1 protein KW - cytochrome P450 KW - Toxicology Abstracts KW - TCDD KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17900747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Physiological+modeling+of+a+proposed+mechanism+of+enzyme+induction+by+TCDD&rft.au=Kohn%2C+M+C%3BWalker%2C+N+J%3BKim%2C+AH%3BPortier%2C+C+J&rft.aulast=Kohn&rft.aufirst=M&rft.date=2001-05-21&rft.volume=162&rft.issue=3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - TCDD ER - TY - JOUR T1 - An Episomally Maintained MDR1 Gene for Gene Therapy AN - 18076255; 5137767 AB - Potential applications of the MDR1 multidrug transporter in gene therapy include protecting sensitive bone marrow cells against cytotoxic drugs during cancer chemotherapy and serving as a dominant selectable marker when coexpressed with a corrective passenger gene. To address safety concerns associated with integrating viral systems, such as retroviruses, we tested the feasibility of maintaining a nonvirally delivered MDR1 gene (pEpiHaMA) episomally. An MDR1 vector containing the Epstein-Barr virus (EBV) origin of replication (OriP) and its nuclear retention protein (EBNA-1) was transfected into human (KB-3-1) cells. MDR1 was expressed at a higher level in cells carrying the episomal vector, pEpiHaMA, compared with the vector lacking sequences needed for episomal maintenance (pHaMA). Furthermore, more drug-resistant KB-3-1 colonies were obtained on selection after transfection with pEpiHaMA. These observations correlated with longer maintenance of episomes in cells transfected with pEpiHaMA. In addition, episomes could still be recovered for more than 1 month from tumor explants in nude mice that were injected with pEpiHaMA-liposome complexes after drug selection, suggesting that these constructs can be maintained extrachromosomally in vivo.. JF - Human Gene Therapy AU - Lee, CGL AU - Vieira, W D AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, Building 37, Room 1A09, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA, mgottesman@nih.gov Y1 - 2001/05/20/ PY - 2001 DA - 2001 May 20 SP - 945 EP - 953 VL - 12 IS - 8 SN - 1043-0342, 1043-0342 KW - man KW - EBNA-1 protein KW - EBNA1 protein KW - MDR1 gene KW - episomes KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Vectors KW - Liposomes KW - Expression vectors KW - Epstein-Barr virus KW - Gene transfer KW - Multidrug resistance KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18076255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=An+Episomally+Maintained+MDR1+Gene+for+Gene+Therapy&rft.au=Lee%2C+CGL%3BVieira%2C+W+D%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Lee&rft.aufirst=CGL&rft.date=2001-05-20&rft.volume=12&rft.issue=8&rft.spage=945&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Epstein-Barr virus; Gene transfer; Gene therapy; Multidrug resistance; Vectors; Liposomes; Expression vectors ER - TY - JOUR T1 - Trial-Related Discrimination in HIV Vaccine Clinical Trial AN - 18073272; 5124025 AB - Participants in preventive HIV vaccine trials may experience negative social consequences of trial participation, including problems related to a vaccine-induced positive HIV antibody test, yet few vaccine studies have reported on this issue. From October 1995 through November 1998, 1516 AIDS Vaccine Evaluation Group (AVEG) volunteers were assessed for reports of trial-related discrimination (TRD). Ninety TRD events were reported by 76 (5%) of 1516 volunteers. The most commonly reported incidents (n = 52, 57.8%) were negative reactions of friends, family, and co-workers to the volunteer. Few incidents (approximately 10%) were reported as linked to HIV testing. The majority of events (n = 47, 52 %) were described by volunteers as "resolved" at the time of reporting, 36 (40%) as "not resolved," and for 7 (8%) events volunteers did not report resolution status. Reported incidents were analyzed by logistic regression to determine their association with the volunteer's age, sex, race, sexual orientation, and HIV risk category. There was no association between volunteer characteristics and TRD. Logistic regression and analysis of variance (ANOVA) were used to analyze association of trial sites with the number of TRD events reported. After controlling for site variation in data collection and reporting, no significant differences were found between the sites in terms of the number or type of TRD reported. Fears that TRD would be widespread and severe have not been borne out by this analysis. While the results of this study are reassuring, they should be interpreted with caution, as it is unclear whether these results may be extended to phase III trials enrolling large numbers of individuals at higher risk of HIV acquisition. JF - AIDS Research and Human Retroviruses AU - Allen, M AU - Israel, H AU - Rybczyk, K AU - Pugliese, MA AU - Loughran, K AU - Wagner, L AU - Erb, S AD - National Institute of Allergy and Infectious Diseases, 6700-B Rockledge Drive, Room 4218, Bethesda, Maryland 20892-7628, USA Y1 - 2001/05/20/ PY - 2001 DA - 2001 May 20 SP - 667 EP - 674 PB - Mary Ann Liebert, Inc. VL - 17 IS - 8 SN - 0889-2229, 0889-2229 KW - HIV KW - clinical trials KW - discrimination KW - vaccines KW - Risk Abstracts; Virology & AIDS Abstracts KW - Human immunodeficiency virus KW - Prophylaxis KW - Social aspects KW - Vaccines KW - V 22006:AIDS: Other aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18073272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Trial-Related+Discrimination+in+HIV+Vaccine+Clinical+Trial&rft.au=Allen%2C+M%3BIsrael%2C+H%3BRybczyk%2C+K%3BPugliese%2C+MA%3BLoughran%2C+K%3BWagner%2C+L%3BErb%2C+S&rft.aulast=Allen&rft.aufirst=M&rft.date=2001-05-20&rft.volume=17&rft.issue=8&rft.spage=667&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Social aspects; Vaccines; Prophylaxis ER - TY - JOUR T1 - Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. AN - 70884068; 11355958 AB - An analysis of the activity of compounds tested in pre-clinical in vivo and in vitro assays by the National Cancer Institute's Developmental Therapeutics Program was performed. For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. However, for compounds with in vivo activity in at least one-third of tested xenograft models, there was correlation with ultimate activity in at least some Phase II trials. Thus, an efficient means of predicting activity in vivo models remains desirable for compounds with anti-proliferative activity in vitro. For 564 compounds tested in the hollow fibre assay which were also tested against in vivo tumour models, the likelihood of finding xenograft activity in at least one-third of the in vivo models tested rose with increasing intraperitoneal hollow fibre activity, from 8% for all compounds tested to 20% in agents with evidence of response in more than 6 intraperitoneal fibres (P< 0.0001). Intraperitoneal hollow fibre activity was also found to be a better predictor of xenograft activity than either subcutaneous hollow fibre activity or intraperitoneal plus subcutaneous activity combined. Since hollow fibre activity was a useful indicator of potential in vivo response, correlates with hollow fibre activity were examined for 2304 compounds tested in both the NCI 60 cell line in vitro cancer drug screen and hollow fibre assay. A positive correlation was found for histologic selectivity between in vitro and hollow fibre responses. The most striking correlation was between potency in the 60 cell line screen and hollow fibre activity; 56% of compounds with mean 50% growth inhibition below 10(-7.5) M were active in more than 6 intraperitoneal fibres whereas only 4% of compounds with a potency of 10(-4) M achieved the same level of hollow fibre activity (P< 0.0001). Structural parameters of the drugs analysed included compound molecular weight and hydrogen-bonding factors, both of which were found to be predictive of hollow fibre activity. Copyright 2001 Cancer Research Campaign. JF - British journal of cancer AU - Johnson, J I AU - Decker, S AU - Zaharevitz, D AU - Rubinstein, L V AU - Venditti, J M AU - Schepartz, S AU - Kalyandrug, S AU - Christian, M AU - Arbuck, S AU - Hollingshead, M AU - Sausville, E A AD - Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001/05/18/ PY - 2001 DA - 2001 May 18 SP - 1424 EP - 1431 VL - 84 IS - 10 SN - 0007-0920, 0007-0920 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - United States KW - Animals KW - Clinical Trials, Phase II as Topic KW - Humans KW - National Institutes of Health (U.S.) KW - Transplantation, Heterologous KW - Disease Models, Animal KW - Mice KW - Models, Biological KW - Drug Screening Assays, Antitumor KW - Clinical Trials as Topic KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70884068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Relationships+between+drug+activity+in+NCI+preclinical+in+vitro+and+in+vivo+models+and+early+clinical+trials.&rft.au=Johnson%2C+J+I%3BDecker%2C+S%3BZaharevitz%2C+D%3BRubinstein%2C+L+V%3BVenditti%2C+J+M%3BSchepartz%2C+S%3BKalyandrug%2C+S%3BChristian%2C+M%3BArbuck%2C+S%3BHollingshead%2C+M%3BSausville%2C+E+A&rft.aulast=Johnson&rft.aufirst=J&rft.date=2001-05-18&rft.volume=84&rft.issue=10&rft.spage=1424&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Ann Oncol. 1999 Nov;10(11):1287-91 [10631454] J Comb Chem. 1999 Jan;1(1):55-68 [10746014] Cancer Chemother Rep. 1966 Oct;50(7):349-96 [5331634] Semin Oncol. 1981 Dec;8(4):349-61 [7323809] Adv Pharmacol Chemother. 1984;20:1-20 [6398966] Cancer Res. 1988 Feb 1;48(3):589-601 [3335022] J Natl Cancer Inst. 1989 Jul 19;81(14):1088-92 [2738938] Eur J Cancer. 1990;26(8):901-5 [2145936] J Natl Cancer Inst. 1991 Jun 5;83(11):757-66 [2041050] Cancer Res. 1998 Dec 1;58(23):5263-6 [9850044] Cancer Res. 1999 Oct 1;59(19):4770-5 [10519381] Comment In: Br J Cancer. 2001 May 18;84(10):1289-90 [11355935] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of the functional epitopes of human interleukin-18-binding protein by site-directed mutagenesis. AN - 70850426; 11278524 AB - The human interleukin (IL)-18-binding protein (hIL-18BP) is a naturally occurring antagonist of IL-18, a proinflammatory cytokine that is related to IL-1beta and has an important role in defense against microbial invaders. As its name implies, the hIL-18BP binds to IL-18 with high affinity and prevents the interaction of IL-18 with its receptor. We genetically modified the C terminus of hIL-18BP by appending a 15-amino acid biotinylation recognition site and a six-histidine tag and then performed site-directed mutagenesis to determine the functional epitopes that mediate efficient binding to IL-18. The mutated IL-18BPs were secreted from mammalian cells, captured by metal affinity chromatography, biotinylated in situ, eluted, and immobilized on streptavidin-coated chips. Using surface plasmon resonance, we identified seven amino acids of hIL-18BP which, when changed individually to alanine, caused an 8-750-fold decrease in binding affinity, largely because of increased off-rates. These seven amino acids localized to the predicted beta-strand c and d of hIL-18BP immunoglobulin-like domain, and most had hydrophobic side chains. Just two amino acids, tyrosine 97 and phenylalanine 104, contributed approximately 50% of the binding free energy. Information obtained from these studies could contribute to the design of molecular antagonists of IL-18 for treatment of inflammatory diseases. JF - The Journal of biological chemistry AU - Xiang, Y AU - Moss, B AD - Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0445, USA. Y1 - 2001/05/18/ PY - 2001 DA - 2001 May 18 SP - 17380 EP - 17386 VL - 276 IS - 20 SN - 0021-9258, 0021-9258 KW - Epitopes KW - 0 KW - Glycoproteins KW - Intercellular Signaling Peptides and Proteins KW - Interleukin-18 KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - interleukin-18 binding protein KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Mammals KW - Humans KW - Amino Acid Sequence KW - Interleukin-18 -- metabolism KW - Biotinylation KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Chromatography, Affinity KW - Recombinant Proteins -- isolation & purification KW - Sequence Alignment KW - Kinetics KW - Restriction Mapping KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Epitopes -- chemistry KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Cell Line KW - Glycoproteins -- immunology KW - Glycoproteins -- chemistry KW - Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70850426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Determination+of+the+functional+epitopes+of+human+interleukin-18-binding+protein+by+site-directed+mutagenesis.&rft.au=Xiang%2C+Y%3BMoss%2C+B&rft.aulast=Xiang&rft.aufirst=Y&rft.date=2001-05-18&rft.volume=276&rft.issue=20&rft.spage=17380&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets AN - 17876399; 5118387 AB - Although the source of embryonic stem (ES) cells present ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of pancreatic islets. We have generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo. When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization. JF - Science (Washington) AU - Lumelsky, N AU - Blondel, O AU - Laeng, P AU - Velasco, I AU - Ravin, R AU - McKay, R AD - Lab. Mol. Biol., Natl. Inst. Neurol. Disorders and Stroke, NIH, Bethesda, MD 20892-4092, USA, mckay@codon.nih.gov Y1 - 2001/05/18/ PY - 2001 DA - 2001 May 18 SP - 1389 EP - 1394 PB - American Association for the Advancement of Science VL - 292 IS - 5520 SN - 0036-8075, 0036-8075 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Diabetes mellitus KW - Stem cells KW - Pancreas KW - Islet cells KW - Insulin KW - W3 33235:New cell lines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17876399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Differentiation+of+embryonic+stem+cells+to+insulin-secreting+structures+similar+to+pancreatic+islets&rft.au=Lumelsky%2C+N%3BBlondel%2C+O%3BLaeng%2C+P%3BVelasco%2C+I%3BRavin%2C+R%3BMcKay%2C+R&rft.aulast=Lumelsky&rft.aufirst=N&rft.date=2001-05-18&rft.volume=292&rft.issue=5520&rft.spage=1389&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Diabetes mellitus; Stem cells; Insulin; Islet cells; Pancreas ER - TY - JOUR T1 - Measures of maternal tobacco exposure and infant birth weight at term. AN - 70896320; 11384951 AB - This study was undertaken to determine the relation between self-reported number of cigarettes smoked per day and urine cotinine concentration during pregnancy and to examine the relations between these two measures of tobacco exposure and birth weight. Data were obtained from the Smoking Cessation in Pregnancy project, conducted between 1987 and 1991. Cigarette smoking information and urine cotinine concentration were collected for 3,395 self-reported smokers who were receiving prenatal care at public clinics in three US states (Colorado, Maryland, and Missouri) and who delivered term infants. General linear models were used to quantify urine cotinine variability explained by the number of cigarettes smoked per day and to generate mean adjusted birth weights for women with different levels of tobacco exposure. Self-reported number of cigarettes smoked per day explained only 13.9% of the variability in urine cotinine concentration. Birth weight declined as tobacco exposure increased; however, the relation was not linear. The sharpest declines in birth weight occurred at low levels of exposure. Furthermore, urine cotinine concentration did not explain more variability in birth weight than did number of cigarettes smoked. These findings should be considered by researchers studying the effects of smoking reduction on birth outcomes. JF - American journal of epidemiology AU - England, L J AU - Kendrick, J S AU - Gargiullo, P M AU - Zahniser, S C AU - Hannon, W H AD - Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, GA, USA. englandl@mail.nih.gov Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 954 EP - 960 VL - 153 IS - 10 SN - 0002-9262, 0002-9262 KW - Cotinine KW - K5161X06LL KW - Index Medicus KW - Cotinine -- urine KW - Epidemiologic Studies KW - Humans KW - Adult KW - Infant, Newborn KW - Adolescent KW - Male KW - Female KW - Pregnancy KW - Infant, Low Birth Weight KW - Smoking -- adverse effects KW - Birth Weight -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70896320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Measures+of+maternal+tobacco+exposure+and+infant+birth+weight+at+term.&rft.au=England%2C+L+J%3BKendrick%2C+J+S%3BGargiullo%2C+P+M%3BZahniser%2C+S+C%3BHannon%2C+W+H&rft.aulast=England&rft.aufirst=L&rft.date=2001-05-15&rft.volume=153&rft.issue=10&rft.spage=954&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 2003 Jan 1;157(1):86-7; author reply 87-8 [12505898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation nonresponsive cells owe their resistance to lack of p65/nuclear factor-kappaB activation. AN - 70886272; 11358840 AB - Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. Inhibition of AP-1 is invariably accompanied by inhibition of nuclear factor-kappaB (NF-kappaB) when transformation is suppressed, suggesting that NF-kappaB may also play a role in neoplastic transformation. We report here that transactivation of NF-kappaB is inducible by tumor promoters in P+ but not in P- JB6 cells. Inhibition of NF-kappaB using a nondegradable mutant of IkappaBalpha suppressed inducible anchorage-independent transformation of P+ JB6 cells, suggesting that NF-kappaB activation is required for tumor promotion. Induced degradation of IkappaBalpha occurred in both P+ and P- JB6 cells, indicating that failure to activate NF-kappaB in P- JB6 cells cannot be attributed to failure to degrade IkappaBalpha. Slightly higher levels of nuclear p65 were seen in P+ than in P- JB6 cells. The p65-specific DNA binding activity was also higher in P+ cells upon induction by tumor necrosis factor-alpha, suggesting that differential NF-kappaB activation may be attributable to changes in p65 activity. Transactivation of p65 protein was substantially higher in P+ than in P- JB6 cells, as determined by assay of Gal4-p65 fusion constructs. Thus activated, p65 may be a limiting factor for NF-kappaB activation and transformation responses. Stable expression of p65 in P- JB6 cells conferred not only inducible NF-kappaB and AP-1 activation but also transformation response to tumor promoters. Therefore, p65/NF-kappaB appears to be not only necessary for but also sufficient to confer tumor promotion response. Although stable expression of p65 in P- cells produced p65 increases in whole cell extracts, only the transfectants exhibiting increased nuclear p65 showed transformation response. Thus, elevation of nuclear p65 appears to be a necessary step for a transformation response. The P-/p65 transfectants showing acquired transformation response also showed elevated p65-specific transactivation response, thus recapitulating the NF-kappaB phenotypes seen in P+ cells. Expression of a transactivation-deficient mutant of Jun or dominant-negative extracellular signal-regulated kinase suppressed both AP-1 activation and p65-specific transactivation in JB6 cells, suggesting that AP-1 activity is needed for p65 transactivation and consequently for NF-kappaB activation. Thus, the transformation nonresponsive P- JB6 cells owe their resistance to lack of NF-kappaB activation and p65 transactivation that appears in turn to be attributable to insufficient AP-1 activation. JF - Cancer research AU - Hsu, T C AU - Nair, R AU - Tulsian, P AU - Camalier, C E AU - Hegamyer, G A AU - Young, M R AU - Colburn, N H AD - Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 4160 EP - 4168 VL - 61 IS - 10 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - I-kappa B Proteins KW - NF-kappa B KW - NF-kappa B p50 Subunit KW - NFKBIA protein, human KW - Nfkbia protein, mouse KW - Transcription Factor AP-1 KW - Transcription Factor RelA KW - Tumor Necrosis Factor-alpha KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Carcinogens -- pharmacology KW - Cell Nucleus -- metabolism KW - Skin -- metabolism KW - DNA -- metabolism KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - DNA-Binding Proteins -- genetics KW - Mice KW - Transcription Factor AP-1 -- physiology KW - Transcriptional Activation KW - Skin -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Skin -- cytology KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - NF-kappa B -- biosynthesis KW - Cell Transformation, Neoplastic -- metabolism KW - Cell Transformation, Neoplastic -- drug effects KW - NF-kappa B -- physiology KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70886272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Transformation+nonresponsive+cells+owe+their+resistance+to+lack+of+p65%2Fnuclear+factor-kappaB+activation.&rft.au=Hsu%2C+T+C%3BNair%2C+R%3BTulsian%2C+P%3BCamalier%2C+C+E%3BHegamyer%2C+G+A%3BYoung%2C+M+R%3BColburn%2C+N+H&rft.aulast=Hsu&rft.aufirst=T&rft.date=2001-05-15&rft.volume=61&rft.issue=10&rft.spage=4160&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic progression and heterogeneity associated with the development of esophageal squamous cell carcinoma. AN - 70872228; 11358832 AB - Esophageal squamous cell carcinoma is a common fatal cancer, and Shanxi province, a region in north-central China, has some of the highest esophageal cancer rates in the world. Chromosomal regions with frequent allelic loss may point to major susceptibility genes that will assist us in understanding the molecular events involved in esophageal carcinogenesis and may serve as the basis for the development of markers for genetic susceptibility and screening for early detection of this cancer. This study was designed to identify events in the molecular progression of precursor and invasive lesions of squamous esophageal cancer. Twelve marker loci identified during our previous studies as having some of the highest rates of loss of heterozygosity (LOH) in invasive esophageal cancer were evaluated in laser-microdissected DNA obtained from low- and high-grade dysplastic lesions and invasive tumor foci from 10 fully embedded esophageal resection specimens. Each resection specimen contained a spectrum of disease, from epithelium that appeared histologically normal to invasive cancer, including a single dominant tumor surrounded by a region of precursor lesions (low- and high-grade dysplasia) and occasional "remote," nonadjacent precancerous foci. Using the 12 polymorphic markers, LOH was found in all of the three stages of disease. The frequency of LOH for all of the markers together increased with increasing disease severity. Among the informative low-grade dysplasia samples, LOH was detected with markers D3S1766 (3p), D4S2632 (4p), D9S910 (9q), and D13S1493 (13q), suggesting that LOH at these loci may be associated with early stages of tumor initiation and/or progression. LOH was detected among the informative high-grade (but not low-grade) dysplasia samples for the other eight markers tested, suggesting that LOH at these loci may occur later in the neoplastic process. In addition to the association between disease progression and these genetic changes, considerable genetic heterogeneity was found in each fully embedded resection specimen both between and within geographically separate neoplastic lesions. JF - Cancer research AU - Roth, M J AU - Hu, N AU - Emmert-Buck, M R AU - Wang, Q H AU - Dawsey, S M AU - Li, G AU - Guo, W J AU - Zhang, Y Z AU - Taylor, P R AD - Cancer Prevention Studies Branch, National Cancer Institute, 6006 Executive Plaza, Bethesda, MD 20892, USA. mr166i@nih.gov Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 4098 EP - 4104 VL - 61 IS - 10 SN - 0008-5472, 0008-5472 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Precancerous Conditions -- genetics KW - Humans KW - Adult KW - Disease Progression KW - DNA, Neoplasm -- genetics KW - Aged KW - Middle Aged KW - Precancerous Conditions -- pathology KW - Male KW - Female KW - Loss of Heterozygosity KW - Carcinoma, Squamous Cell -- pathology KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Esophageal Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70872228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Genetic+progression+and+heterogeneity+associated+with+the+development+of+esophageal+squamous+cell+carcinoma.&rft.au=Roth%2C+M+J%3BHu%2C+N%3BEmmert-Buck%2C+M+R%3BWang%2C+Q+H%3BDawsey%2C+S+M%3BLi%2C+G%3BGuo%2C+W+J%3BZhang%2C+Y+Z%3BTaylor%2C+P+R&rft.aulast=Roth&rft.aufirst=M&rft.date=2001-05-15&rft.volume=61&rft.issue=10&rft.spage=4098&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the ITS2-proximal stem and evidence for indirect recognition of processing sites in pre-rRNA processing in yeast. AN - 70868329; 11353080 AB - Eucaryotic ribosome biogenesis involves many cis-acting sequences and trans-acting factors, including snoRNAS: We have used directed mutagenesis of rDNA plasmids in yeast to identify critical sequence and structural elements within and flanking the ITS2-proximal stem. This base paired structure, present in the mature ribosome, is formed between the 5'-end of 25S and the 3'-end of 5.8S rRNAS: Previously we demonstrated that formation of this structure was critical for pre-rRNA processing in yeast. Here we show that there are no sequence-specific recognition elements within the ITS2-proximal stem, rather the structure of this stem is critical for processing. This stem cannot exceed a specific length, but there are different length restrictions for different regions within this tripartite stem. Neither the conserved unpaired nucleotides within the stem nor the sequence of the mature rRNA at the processing sites are required for processing. Collectively, these results suggest a measuring model whereby initial cleavage within ITS2 at the C2 processing site and termination of subsequent exonuclease activity yielding the mature termini are affected by the relative position of sequence and structural elements within the ITS2-proximal stem. JF - Nucleic acids research AU - Côté, C A AU - Peculis, B A AD - Genetics and Biochemistry Branch, 10 Center Drive, National Institutes of Health, NIDDK, Bethesda, MD 20892-1766, USA. Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 2106 EP - 2116 VL - 29 IS - 10 KW - Oligonucleotides KW - 0 KW - RNA Precursors KW - RNA, Fungal KW - RNA, Ribosomal KW - RNA, Ribosomal, 5.8S KW - RNA, ribosomal, 25S KW - 130527-23-0 KW - Index Medicus KW - Ribosomes -- metabolism KW - RNA, Fungal -- genetics KW - Plasmids -- genetics KW - RNA Stability KW - RNA, Fungal -- metabolism KW - RNA, Ribosomal, 5.8S -- metabolism KW - Binding Sites KW - Base Pairing KW - Ribosomes -- chemistry KW - Base Sequence KW - Conserved Sequence -- genetics KW - Ribosomes -- genetics KW - RNA, Ribosomal, 5.8S -- chemistry KW - Models, Genetic KW - RNA, Ribosomal, 5.8S -- genetics KW - Mutation -- genetics KW - Substrate Specificity KW - Oligonucleotides -- genetics KW - RNA, Fungal -- chemistry KW - Saccharomyces cerevisiae -- genetics KW - RNA, Ribosomal -- chemistry KW - RNA Precursors -- metabolism KW - RNA, Ribosomal -- metabolism KW - RNA, Ribosomal -- genetics KW - RNA Precursors -- chemistry KW - RNA Precursors -- genetics KW - Nucleic Acid Conformation KW - RNA Processing, Post-Transcriptional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70868329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Role+of+the+ITS2-proximal+stem+and+evidence+for+indirect+recognition+of+processing+sites+in+pre-rRNA+processing+in+yeast.&rft.au=C%C3%B4t%C3%A9%2C+C+A%3BPeculis%2C+B+A&rft.aulast=C%C3%B4t%C3%A9&rft.aufirst=C&rft.date=2001-05-15&rft.volume=29&rft.issue=10&rft.spage=2106&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1981 Jun 25;9(12):2913-32 [7024907] RNA. 2000 Dec;6(12):1698-703 [11142370] Nucleic Acids Res. 1982 Sep 11;10(17):5273-83 [6292836] Biochem J. 1985 Jul 1;229(1):1-17 [3899100] J Mol Biol. 1990 Feb 20;211(4):699-712 [2179564] EMBO J. 1990 Dec;9(12):3989-96 [2249660] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3962-6 [2023944] J Mol Biol. 1992 Feb 20;223(4):899-910 [1538404] Cell. 1993 Jun 18;73(6):1233-45 [8513505] Nucleic Acids Res. 1993 Jul 1;21(13):3055-74 [8332527] J Mol Biol. 1995 Jun 30;250(1):24-36 [7602595] J Mol Evol. 1995 Jun;40(6):640-51 [7643415] Genes Dev. 1996 Feb 15;10(4):502-13 [8600032] Nucleic Acids Res. 1996 Aug 1;24(15):2857-67 [8760866] Mol Cell Biol. 1997 Jul;17(7):3702-13 [9199304] Cell. 1997 Nov 14;91(4):457-66 [9390555] Electrophoresis. 1998 Oct;19(14):2391-5 [9820955] Int J Parasitol. 1998 Nov;28(11):1765-73 [9846614] RNA. 1998 Dec;4(12):1610-22 [9848657] EMBO J. 1999 Oct 1;18(19):5399-410 [10508172] Nucleic Acids Res. 1999 Dec 1;27(23):4533-40 [10556307] Mol Cell Biol. 1999 Dec;19(12):7897-912 [10567516] Annu Rev Genet. 1999;33:261-311 [10690410] Science. 2000 Aug 11;289(5481):905-20 [10937989] Cell. 2000 Sep 1;102(5):615-23 [11007480] Nucleic Acids Res. 1981 Oct 10;9(19):4847-62 [7312619] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I clinical trial of alitretinoin and tamoxifen in breast cancer patients: toxicity, pharmacokinetic, and biomarker evaluations. AN - 70852361; 11352969 AB - To determine the overall and dose-limiting toxicities (DLTs) of alitretinoin (9-cis-retinoic acid) in combination with tamoxifen and the pharmacokinetics of alitretinoin alone and when combined with tamoxifen in patients with metastatic breast cancer. The effect of tamoxifen and alitretinoin on MIB-1, a marker of proliferation, in unaffected breast tissue was explored. Eligible patients had metastatic breast cancer. Previous tamoxifen therapy was allowed. Planned dose levels for alitretinoin ranged from 50 to 140 mg/m2/d with 20 mg/d tamoxifen in all patients after 4 weeks of alitretinoin as a single agent. Plasma concentrations of alitretinoin and retinol were measured at baseline and after 1, 2, and 3 months. Breast core biopsies were obtained at baseline and after 2 months of therapy. Twelve patients with metastatic breast cancer received a total of 86 cycles of therapy. At 90 mg/m2/d, three of five patients experienced a DLT: grade 3 headache, grade 3 hypercalcemia, and grade 3 noncardiogenic pulmonary edema. At 70 mg/m2/d, one of six patients experienced a DLT (headache), and this level was considered the maximal tolerated dose in this study. Three toxicities occurred that had not been reported previously with alitretinoin: an asymptomatic delay in dark adaptation, a marked decrease in high-density lipoprotein cholesterol, and the occurrence of enthesopathy. Two of the nine assessable patients had a durable clinical response: one partial response and stable disease for 18 months and one complete response in continuous remission for 48+ months. Both responding patients were estrogen receptor-positive and had had previous tamoxifen therapy. There was a high degree of interpatient variability of plasma alitretinoin concentrations, although a significant decline in alitretinoin plasma levels over time was observed. MIB-1 scores declined in four of the eight paired breast specimens obtained. The combination of tamoxifen and alitretinoin is well tolerated and has antitumor activity in metastatic breast cancer. The recommended phase II dose is 70 mg/m2/d with 20 mg/d tamoxifen. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Lawrence, J A AU - Adamson, P C AU - Caruso, R AU - Chow, C AU - Kleiner, D AU - Murphy, R F AU - Venzon, D J AU - Shovlin, M AU - Noone, M AU - Merino, M AU - Cowan, K H AU - Kaiser, M AU - O'Shaughnessy, J AU - Zujewski, J AD - Medicine Branch, and Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 2754 EP - 2763 VL - 19 IS - 10 SN - 0732-183X, 0732-183X KW - Antigens, Nuclear KW - 0 KW - Antineoplastic Agents KW - Biomarkers KW - Ki-67 Antigen KW - Nuclear Proteins KW - Tamoxifen KW - 094ZI81Y45 KW - alitretinoin KW - 1UA8E65KDZ KW - Tretinoin KW - 5688UTC01R KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Nuclear Proteins -- isolation & purification KW - Cholesterol -- blood KW - Area Under Curve KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Female KW - Chromatography, High Pressure Liquid KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Tamoxifen -- therapeutic use KW - Antineoplastic Agents -- pharmacokinetics KW - Breast Neoplasms -- metabolism KW - Antineoplastic Agents -- therapeutic use KW - Tretinoin -- pharmacokinetics KW - Tretinoin -- therapeutic use KW - Tretinoin -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70852361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+clinical+trial+of+alitretinoin+and+tamoxifen+in+breast+cancer+patients%3A+toxicity%2C+pharmacokinetic%2C+and+biomarker+evaluations.&rft.au=Lawrence%2C+J+A%3BAdamson%2C+P+C%3BCaruso%2C+R%3BChow%2C+C%3BKleiner%2C+D%3BMurphy%2C+R+F%3BVenzon%2C+D+J%3BShovlin%2C+M%3BNoone%2C+M%3BMerino%2C+M%3BCowan%2C+K+H%3BKaiser%2C+M%3BO%27Shaughnessy%2C+J%3BZujewski%2C+J&rft.aulast=Lawrence&rft.aufirst=J&rft.date=2001-05-15&rft.volume=19&rft.issue=10&rft.spage=2754&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of cytochromes P50 1A1, 1A2, and 1B1. AN - 70851782; 11358806 AB - The phytochemical dibenzoylmethane (DBM) has been shown to prevent polycyclic aromatic hydrocarbon (PAH)-induced tumorigenesis in rodents. However, the biochemical basis of this activity is unclear. We have therefore investigated the effects of DBM on the activity and expression of carcinogen-activating enzymes, the cytochromes P450 (CYP) 1A1, 1A2, and 1B1. Oral administration of DBM to female Sprague Dawley rats inhibited the increase in hepatic enzyme activity and mRNA levels of CYP1A1, 1A2, and 1B1 caused by the PAH 7,12-dimethylbenz[a]anthracene (DMBA). However, DBM administration alone caused an increase in both activity and expression in the liver, albeit to levels much lower than that induced by DMBA. To characterize the molecular mechanisms involved in this dual action of DBM, we examined the effects of DBM in vitro. In HepG2 human hepatoma cells, DBM inhibited DMBA- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced enzyme activity and CYP1A1, 1A2, and 1B1 mRNA levels, whereas DBM itself induced activity and mRNA expression. Modulation of CYP1A1 expression by DBM occurred at the transcriptional level, as transient transfection assays demonstrated. Because the transcription of CYP1A1 is regulated by the aryl hydrocarbon receptor (AhR), we investigated the effect of DBM on AhR activation. DBM inhibited TCCD-induced DNA-binding of the AhR to the xenobiotic-responsive element (XRE) of CYP1A1 as measured by electrophoretic mobility shift assay. These data suggest that the chemopreventive activity of DBM results from its ability to affect Phase 1 enzyme expression by modulation of AhR function. JF - Cancer research AU - MacDonald, C J AU - Ciolino, H P AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702-1201, USA. Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 3919 EP - 3924 VL - 61 IS - 10 SN - 0008-5472, 0008-5472 KW - Benzoates KW - 0 KW - Carcinogens KW - Chalcones KW - Isoenzymes KW - Nucleic Acid Synthesis Inhibitors KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Dactinomycin KW - 1CC1JFE158 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - dibenzoylmethane KW - ANS7ME8OKC KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Transcription, Genetic -- drug effects KW - Carcinogens -- pharmacokinetics KW - Humans KW - RNA, Messenger -- genetics KW - Isoenzymes -- genetics KW - RNA, Messenger -- biosynthesis KW - Isoenzymes -- metabolism KW - Rats KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Dactinomycin -- pharmacology KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Biotransformation KW - Liver -- drug effects KW - Isoenzymes -- biosynthesis KW - Binding, Competitive KW - Female KW - Receptors, Aryl Hydrocarbon -- physiology KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Benzoates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70851782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Dibenzoylmethane+modulates+aryl+hydrocarbon+receptor+function+and+expression+of+cytochromes+P50+1A1%2C+1A2%2C+and+1B1.&rft.au=MacDonald%2C+C+J%3BCiolino%2C+H+P%3BYeh%2C+G+C&rft.aulast=MacDonald&rft.aufirst=C&rft.date=2001-05-15&rft.volume=61&rft.issue=10&rft.spage=3919&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced tumor promotion by 17 beta-estradiol in female Sprague--Dawley rats. AN - 70838338; 11350210 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in female but not in male rats. In an initiation-promotion model, ovariectomy inhibits TCDD-induced cell replication and reduces both TCDD-induced tumor formation and the promotion of enzyme-altered hepatocellular foci (AHF). The aim of this study was to determine the involvement of the ovarian hormone 17 beta-estradiol in the induction of cell proliferation and development of putative preneoplastic AHF following chronic exposure to TCDD. Diethylnitrosamine (DEN)-initiated ovariectomized (OVX) female rats were treated with TCDD for 20 or 30 weeks in the presence and absence of 17 beta-estradiol administered continuously by implanted 90-day release pellets. Following 20 weeks of treatment, cell proliferation in TCDD-treated rats was decreased regardless of ovarian hormones. Following 30 weeks of exposureTCDD, only significantly induced cell proliferation in OVX rats receiving supplemental 17 beta-estradiol. These data demonstrate that the the transitory mitoinhibition of cell replication by TCDD is not hormonally responsive, but that induction of cell replication at later time points is. TCDD exposure resulted in elevated AHF expressing gamma-glutamyltranspeptidase (GGT) in intact, but not OVX rats at both time points. TCDD also induced GGT-positive AHF in 17 beta-estradiol-supplemented OVX rats. TCDD induced AHF expressing the placental form of glutathione-S-transferase (PGST) in both intact and OVX rats regardless of 17 beta-estradiol exposure, indicating that the modulating effect of 17 beta-estradiol on AHF was specific to the GGT-positive phenotype. Copyright 2001 Academic Press. JF - Toxicology and applied pharmacology AU - Wyde, M E AU - Eldridge, S R AU - Lucier, G W AU - Walker, N J AD - National Institute of Environmental Health Sciences, Environmental Toxicology Program, Research Triangle Park, North Carolina 22709, USA. Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 7 EP - 17 VL - 173 IS - 1 SN - 0041-008X, 0041-008X KW - Polychlorinated Dibenzodioxins KW - 0 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Estradiol KW - 4TI98Z838E KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Liver -- pathology KW - Liver -- enzymology KW - Placenta -- enzymology KW - gamma-Glutamyltransferase -- analysis KW - Glutathione Transferase -- metabolism KW - Cell Division -- drug effects KW - Ovariectomy KW - Diethylnitrosamine -- pharmacology KW - Female KW - Liver Neoplasms -- pathology KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Estradiol -- pharmacology KW - Liver Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70838338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Regulation+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin-induced+tumor+promotion+by+17+beta-estradiol+in+female+Sprague--Dawley+rats.&rft.au=Wyde%2C+M+E%3BEldridge%2C+S+R%3BLucier%2C+G+W%3BWalker%2C+N+J&rft.aulast=Wyde&rft.aufirst=M&rft.date=2001-05-15&rft.volume=173&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modifications in the CD36 binding domain of the Plasmodium falciparum variant antigen are responsible for the inability of chondroitin sulfate A adherent parasites to bind CD36. AN - 70823930; 11342458 AB - Adhesion of mature Plasmodium falciparum parasitized erythrocytes to microvascular endothelial cells or to placenta contributes directly to the virulence and severe pathology of P falciparum malaria. Whereas CD36 is the major endothelial receptor for microvasculature sequestration, infected erythrocytes adhering in the placenta bind chondroitin sulfate A (CSA) but not CD36. Binding to both receptors is mediated by different members of the large and diverse protein family P falciparum erythrocyte membrane protein-1 (PfEMP-1) and involves different regions of the molecule. The PfEMP-1-binding domain for CD36 resides in the cysteine-rich interdomain region 1 (CIDR-1). To explore why CSA-binding parasites do not bind CD36, CIDR-1 domains from CD36- or CSA-binding parasites were expressed in mammalian cells and tested for adhesion. Although CIDR-1 domains from CD36-adherent strains strongly bound CD36, those from CSA-adherent parasites did not. The CIDR-1 domain has also been reported to bind CSA. However, none of the CIDR-1 domains tested bound CSA. Chimeric proteins between CIDR-1 domains that bind or do not bind CD36 and mutagenesis experiments revealed that modifications in the minimal CD36-binding region (M2 region) are responsible for the inability of CSA-selected parasites to bind CD36. One of these modifications, mapped to a 3-amino acid substitution in the M2 region, ablated binding in one variant and largely reduced binding of another. These findings provide a molecular explanation for the inability of placental sequestered parasites to bind CD36 and provide additional insight into critical residues for the CIDR-1/CD36 interaction. JF - Blood AU - Gamain, B AU - Smith, J D AU - Miller, L H AU - Baruch, D I AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 3268 EP - 3274 VL - 97 IS - 10 SN - 0006-4971, 0006-4971 KW - Antigens, CD36 KW - 0 KW - Antigens, Protozoan KW - Protozoan Proteins KW - Recombinant Fusion Proteins KW - erythrocyte membrane protein 1, Plasmodium falciparum KW - Chondroitin Sulfates KW - 9007-28-7 KW - Cysteine KW - K848JZ4886 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cysteine -- analysis KW - Erythrocytes -- physiology KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Erythrocytes -- parasitology KW - Antigens, Protozoan -- genetics KW - Conserved Sequence KW - Transfection KW - Molecular Sequence Data KW - CHO Cells KW - Erythrocyte Membrane KW - Antigens, Protozoan -- chemistry KW - Cell Line KW - Cricetinae KW - Protozoan Proteins -- chemistry KW - Antigens, CD36 -- metabolism KW - Protozoan Proteins -- genetics KW - Plasmodium falciparum -- immunology KW - Chondroitin Sulfates -- metabolism KW - Plasmodium falciparum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70823930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Modifications+in+the+CD36+binding+domain+of+the+Plasmodium+falciparum+variant+antigen+are+responsible+for+the+inability+of+chondroitin+sulfate+A+adherent+parasites+to+bind+CD36.&rft.au=Gamain%2C+B%3BSmith%2C+J+D%3BMiller%2C+L+H%3BBaruch%2C+D+I&rft.aulast=Gamain&rft.aufirst=B&rft.date=2001-05-15&rft.volume=97&rft.issue=10&rft.spage=3268&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus. AN - 70817986; 11342455 AB - There is substantial evidence that Kaposi sarcoma-associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1% O(2)) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS. JF - Blood AU - Davis, D A AU - Rinderknecht, A S AU - Zoeteweij, J P AU - Aoki, Y AU - Read-Connole, E L AU - Tosato, G AU - Blauvelt, A AU - Yarchoan, R AD - HIV and AIDS Malignancy Branch, the Dermatology Branch, and the Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. dadavis@helix.nih.gov Y1 - 2001/05/15/ PY - 2001 DA - 2001 May 15 SP - 3244 EP - 3250 VL - 97 IS - 10 SN - 0006-4971, 0006-4971 KW - Glycoproteins KW - 0 KW - Interleukin-6 KW - K8.1 protein, Human herpesvirus 8 KW - ORF59 protein, Human herpesvirus 8 KW - Viral Proteins KW - Cobalt KW - 3G0H8C9362 KW - cobaltous chloride KW - EVS87XF13W KW - Deferoxamine KW - J06Y7MXW4D KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Blotting, Western KW - B-Lymphocytes -- virology KW - Deferoxamine -- pharmacology KW - Capsid -- analysis KW - Tumor Cells, Cultured KW - Interleukin-6 -- secretion KW - Glycoproteins -- analysis KW - Humans KW - Viral Proteins -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cobalt -- pharmacology KW - Cell Line KW - Virus Replication -- drug effects KW - Herpesvirus 8, Human -- physiology KW - Herpesvirus 8, Human -- isolation & purification KW - Cell Hypoxia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70817986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Hypoxia+induces+lytic+replication+of+Kaposi+sarcoma-associated+herpesvirus.&rft.au=Davis%2C+D+A%3BRinderknecht%2C+A+S%3BZoeteweij%2C+J+P%3BAoki%2C+Y%3BRead-Connole%2C+E+L%3BTosato%2C+G%3BBlauvelt%2C+A%3BYarchoan%2C+R&rft.aulast=Davis&rft.aufirst=D&rft.date=2001-05-15&rft.volume=97&rft.issue=10&rft.spage=3244&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancing the potency of peptide-pulsed antigen presenting cells by vector-driven hyperexpression of a triad of costimulatory molecules AN - 18076922; 5139048 AB - Recombinant orthopox vectors (both replication-defective fowlpox [rF], and replication competent vaccinia [rV] have been developed that simultaneously express three T-cell costimulatory molecule transgenes. The constituents of this triad of costimulatory molecules (designated TRICOM) are B7-1, ICAM-1, and LFA-3. We have previously shown that infection of murine dendritic cells (DCs) with TRICOM vectors increases their level of expression of the triad of costimulatory molecules and enhances the efficacy of DCs to activate T cells. While DCs are arguably the most potent antigen presenting cell (APC), limitations clearly exist in their use due to the level of effort and cost for their generation. The studies reported here demonstrate that a generic APC population, murine splenocytes, can be made markedly more efficient as APCs by infection with either rF-TRICOM or rV-TRICOM vectors. Infection of splenocytes with either TRICOM vector led to significant improvement of APC capabilities in terms of: (a) enhancement of mixed lymphocyte reactions; (b) a reduction in the amount of signal 1 to activate naive T cells; and (c) a reduction in the amount of APCs required to activate T cells using a constant amount of signal 1. TRICOM-enhanced T-cell activation was shown to correspond to increases in type-1 cytokines and a reduced level of apoptosis, compared with T cells activated with uninfected or control vector-infected splenocytes. In vitro and in vivo experiments compared DCs with TRICOM-infected splenocytes. Infection of splenocytes with TRICOM vectors markedly enhanced their ability to activate T cells to levels approaching that of DCs. These studies thus demonstrate for the first time that an abundant and accessible population of APCs obtainable without lengthy culture or the use of costly exogenous cytokines (in contrast to that of DCs) can be made more potent as APCs with the use of vectors that express a triad of costimulatory molecules. JF - Vaccine AU - Hodge, J W AU - Grosenbach, D W AU - Rad, AN AU - Giuliano, M AU - Sabzevari, H AU - Schlom, J AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Building 10, Room 8B07, 10 Center Drive, Bethesda, MD 20892-1750, USA Y1 - 2001/05/14/ PY - 2001 DA - 2001 May 14 SP - 3552 EP - 3567 VL - 19 IS - 25-26 SN - 0264-410X, 0264-410X KW - mice KW - vectors KW - B7-1 antigen KW - LFA-3 antigen KW - intercellular adhesion molecule 1 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Splenocytes KW - Dendritic cells KW - Lymphocytes T KW - Vaccines KW - Antigen-presenting cells KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews KW - W3 33360:Adjuvants and carriers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18076922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Enhancing+the+potency+of+peptide-pulsed+antigen+presenting+cells+by+vector-driven+hyperexpression+of+a+triad+of+costimulatory+molecules&rft.au=Hodge%2C+J+W%3BGrosenbach%2C+D+W%3BRad%2C+AN%3BGiuliano%2C+M%3BSabzevari%2C+H%3BSchlom%2C+J&rft.aulast=Hodge&rft.aufirst=J&rft.date=2001-05-14&rft.volume=19&rft.issue=25-26&rft.spage=3552&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antigen-presenting cells; Dendritic cells; Lymphocytes T; Splenocytes; Vaccines ER - TY - JOUR T1 - Solution Structure, Backbone Dynamics and Chitin Binding of the Anti-fungal Protein from Streptomyces tendae T901 AN - 17896738; 5130537 AB - AFP1 is a recently discovered anti-fungal, chitin-binding protein from Streptomyces tendae T901. Mature AFP1 comprises 86 residues and exhibits limited sequence similarity to the cellulose-binding domains of bacterial cellulases and xylanases. No similarity to the Cys and Gly-rich domains of plant chitin-binding proteins (e.g. agglutinins, lectins, hevein) is observed. AFP1 is the first chitin-binding protein from a bacterium for which anti-fungal activity was shown. Here, we report the three-dimensional solution structure of AFP1, determined by nuclear magnetic resonance spectroscopy. The protein contains two antiparallel beta -sheets (five and four beta -strands each), that pack against each other in a parallel beta -sandwich. This type of architecture is conserved in the functionally related family II of cellulose-binding domains, albeit with different connectivity. A similar fold is also observed in other unrelated proteins (spore coat protein from Myxococcus xanthus, beta -B sub(2) and gamma -B crystallins from Bos taurus, canavalin from Jack bean). AFP1 is therefore classified as a new member of the beta gamma -crystallin superfamily. The dynamics of the protein was characterized by NMR using amide super(15)N relaxation and solvent exchange data. We demonstrate that the protein exhibits an axially symmetric (oblate-like) rotational diffusion tensor whose principal axis coincides to within 15 parallel with that of the inertial tensor. After completion of the present structure of AFP1, an identical fold was reported for a Streptomyces killer toxin-like protein. Based on sequence comparisons and clustering of conserved residues on the protein surface for different cellulose and chitin-binding proteins, we postulate a putative sugar-binding site for AFP1. The inability of the protein to bind short chitin fragments suggests that certain particular architectural features of the solid chitin surface are crucial for the interaction. Copyright 2001 Academic Press JF - Journal of Molecular Biology AU - Campos-Olivas, R AU - Hrr, I AU - Bormann, C AU - Jung, G AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA Y1 - 2001/05/11/ PY - 2001 DA - 2001 May 11 SP - 765 EP - 782 PB - Academic Press VL - 308 IS - 4 SN - 0022-2836, 0022-2836 KW - binding KW - AFP1 protein KW - solution structure KW - Microbiology Abstracts B: Bacteriology KW - Antifungal agents KW - Chitin KW - Antibiotics KW - Streptomyces tendae KW - J 02781:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17896738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Solution+Structure%2C+Backbone+Dynamics+and+Chitin+Binding+of+the+Anti-fungal+Protein+from+Streptomyces+tendae+T901&rft.au=Campos-Olivas%2C+R%3BHrr%2C+I%3BBormann%2C+C%3BJung%2C+G%3BGronenborn%2C+A+M&rft.aulast=Campos-Olivas&rft.aufirst=R&rft.date=2001-05-11&rft.volume=308&rft.issue=4&rft.spage=765&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2001.4622 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptomyces tendae; Antifungal agents; Antibiotics; Chitin DO - http://dx.doi.org/10.1006/jmbi.2001.4622 ER - TY - JOUR T1 - No association of CCK and CCK(B) receptor polymorphisms with alcohol dependence. AN - 70853546; 11368834 AB - Cholecystokinin (CCK) is the most widely distributed neuropeptide in the central nervous system. One of its several functions is to modulate the release of dopamine in brain areas involved in reinforcement and reward behavior. The aim of this study was to investigate the association of CCK system genes (CCK, CCK(A) and CCK(B) receptor genes) with alcohol dependence using single nucleotide polymorphisms (SNPs) as genetic markers. A total of 257 psychiatrically interviewed Finns were genotyped for CCK (-45C>T), CCK(A) (Val365Ile) and CCK(B) (Val125Ile) receptor polymorphisms. Allele frequencies were compared between 150 unrelated healthy Finnish controls and 107 unrelated alcohol-dependent subjects (DSM-III-R criteria), who were also criminal offenders. The frequency of the CCK -45T allele was not significantly different between controls [0.07] and alcoholics [0.09]. The CCK(B) receptor polymorphism Val125Ile was also not associated with alcoholism and the Ile125 allele frequencies were 0.05 in controls vs. 0.06 in alcohol-dependent subjects. A CCK(A) receptor marker, Val365Ile, was uninformative in this Finnish dataset; all subjects were Val365/Val365 homozygous. The results suggest that CCK -45C>T and CCKBR Val125Ile polymorphisms do not have a major role in alcohol dependence in the population studied. The role of the CCK(A) the receptor in alcohol dependence remains open until additional DNA sequence variants for this gene become available. JF - Psychiatry research AU - Vanakoski, J AU - Virkkunen, M AU - Naukkarinen, H AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. jyrki.vanakoski@kolumbus.fi Y1 - 2001/05/10/ PY - 2001 DA - 2001 May 10 SP - 1 EP - 7 VL - 102 IS - 1 SN - 0165-1781, 0165-1781 KW - DNA Primers KW - 0 KW - Genetic Markers KW - Protein Precursors KW - Receptor, Cholecystokinin B KW - Receptors, Cholecystokinin KW - Index Medicus KW - Alleles KW - Humans KW - Protein Precursors -- genetics KW - Gene Frequency -- genetics KW - Finland -- epidemiology KW - Receptors, Cholecystokinin -- genetics KW - Polymorphism, Genetic -- genetics KW - Receptors, Cholecystokinin -- metabolism KW - Alcoholism -- metabolism KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70853546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=No+association+of+CCK+and+CCK%28B%29+receptor+polymorphisms+with+alcohol+dependence.&rft.au=Vanakoski%2C+J%3BVirkkunen%2C+M%3BNaukkarinen%2C+H%3BGoldman%2C+D&rft.aulast=Vanakoski&rft.aufirst=J&rft.date=2001-05-10&rft.volume=102&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead AN - 17891708; 5126073 AB - Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment. We enrolled 780 children with blood lead levels of 20 to 44 mu g per deciliter (1.0 to 2.1 mu mol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months. During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 mu g per deciliter (0.2 mu mol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 mu g per deciliter [0.2 to 0.3 mu mol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant. Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 mu g per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels. JF - New England Journal of Medicine AU - Rogan, W J AU - Dietrich, K N AU - Ware, J H AU - Dockery, D W AU - Salganik, M AU - Radcliffe, J AU - Jones, R L AU - Ragan, N B AU - Chisolm, JJ Jr AU - Rhoads, G G AD - Epidemiology Branch, National Institute of Environmental Health Sciences, A3-05, P.O. Box 12233, Research Triangle Park, NC 27709, USA, rogan@niehs.nih.gov Y1 - 2001/05/10/ PY - 2001 DA - 2001 May 10 SP - 1421 EP - 1426 VL - 344 IS - 19 SN - 0028-4793, 0028-4793 KW - man KW - chelation therapy KW - cognitive ability KW - succimer KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Poisoning KW - Chelating agents KW - Children KW - Lead KW - Cognitive ability KW - Motor activity KW - Neurotoxicity KW - R2 23060:Medical and environmental health KW - X 24162:Chronic exposure KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17891708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+England+Journal+of+Medicine&rft.atitle=The+effect+of+chelation+therapy+with+succimer+on+neuropsychological+development+in+children+exposed+to+lead&rft.au=Rogan%2C+W+J%3BDietrich%2C+K+N%3BWare%2C+J+H%3BDockery%2C+D+W%3BSalganik%2C+M%3BRadcliffe%2C+J%3BJones%2C+R+L%3BRagan%2C+N+B%3BChisolm%2C+JJ+Jr%3BRhoads%2C+G+G&rft.aulast=Rogan&rft.aufirst=W&rft.date=2001-05-10&rft.volume=344&rft.issue=19&rft.spage=1421&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Children; Lead; Poisoning; Neurotoxicity; Motor activity; Chelating agents; Cognitive ability ER - TY - JOUR T1 - The microenvironment of the tumour-host interface AN - 839664745; 13743687 AB - Throughout the entire process of cancer aetiology, progression and metastasis, the microenvironment of the local host tissue can be an active participant. Invasion occurs within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate migration, and promote proliferation and survival. A new class of cancer therapies that targets this pathological communication interface between tumour cells and host cells is currently under development. JF - Nature AU - Liotta, Lance A AU - Kohn, Elise C AD - Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA PY - 2001 SP - 375 EP - 379 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 411 IS - 6835 SN - 0028-0836, 0028-0836 KW - Ecology Abstracts KW - Cell survival KW - Stroma KW - Metastases KW - Microenvironments KW - Cytokines KW - Enzymes KW - Cell migration KW - Cell proliferation KW - Cancer KW - D 04040:Ecosystem and Ecology Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/839664745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=The+microenvironment+of+the+tumour-host+interface&rft.au=Liotta%2C+Lance+A%3BKohn%2C+Elise+C&rft.aulast=Liotta&rft.aufirst=Lance&rft.date=2001-05-07&rft.volume=411&rft.issue=6835&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35077241 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - Metastases; Stroma; Cell survival; Enzymes; Cytokines; Microenvironments; Cell migration; Cell proliferation; Cancer DO - http://dx.doi.org/10.1038/35077241 ER - TY - JOUR T1 - Confusion after antibiotics. AN - 70852287; 11356440 JF - Lancet (London, England) AU - Gavazzi, C AU - Stacchiotti, S AU - Cavalletti, R AU - Lodi, R AD - Nutrition Support Unit, National Cancer Institute, Via Venezian 1, 20133, Milan, Italy. nutritionunit@yahoo.it Y1 - 2001/05/05/ PY - 2001 DA - 2001 May 05 SP - 1410 VL - 357 IS - 9266 SN - 0140-6736, 0140-6736 KW - Anti-Bacterial Agents KW - 0 KW - Neomycin KW - 1404-04-2 KW - Lactic Acid KW - 33X04XA5AT KW - Vancomycin KW - 6Q205EH1VU KW - Abridged Index Medicus KW - Index Medicus KW - Parenteral Nutrition, Home Total KW - Humans KW - Middle Aged KW - Female KW - Lactobacillus casei KW - Neomycin -- adverse effects KW - Vancomycin -- adverse effects KW - Lactic Acid -- blood KW - Acidosis, Lactic -- chemically induced KW - Anti-Bacterial Agents -- adverse effects KW - Acidosis, Lactic -- therapy KW - Confusion -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70852287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Confusion+after+antibiotics.&rft.au=Gavazzi%2C+C%3BStacchiotti%2C+S%3BCavalletti%2C+R%3BLodi%2C+R&rft.aulast=Gavazzi&rft.aufirst=C&rft.date=2001-05-05&rft.volume=357&rft.issue=9266&rft.spage=1410&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 2001 Nov 24;358(9295):1814 [11734269] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of murine homeodomain protein Dlx3 by protein kinase C. AN - 70833571; 11343707 AB - The Dlx3 homeodomain gene is expressed in terminally differentiated murine epidermal cells. As demonstrated for differentiation-specific granular markers, Dlx3 is activated in primary mouse keratinocytes cultured in vitro by increasing the level of the extracellular Ca(2+). This activation is mediated through a protein kinase C-dependent (PKC) pathway. In this study, we investigated whether PKC can modulate the activity of murine Dlx3 protein. Using in vitro kinase assays, we show that PKC enzymes phosphorylate the Dlx3 protein. Using keratinocyte nuclear extracts for the kinase reaction, we determined that Dlx3 protein is phosphorylated, and the phosphorylation is inhibited by the PKC-specific inhibitor GF109203X, suggesting that Dlx3 is phosphorylated by PKC in vivo. Of the PKC isoforms present in the epidermis, we tested alpha, delta, epsilon and zeta. Dlx3 is primarily phosphorylated by PKC alpha. By deletion and mutational analysis, we show that the serine residue S(138), located in the homeodomain of Dlx3 protein, was specifically phosphorylated by PKC. The phosphorylation of purified Dlx3 proteins by PKC partially inhibited formation of complexes between Dlx3 protein and DNA. These results suggest that Dlx3 protein can be directly phosphorylated by PKC and this affects the DNA binding activity of Dlx3. JF - FEBS letters AU - Park, G T AU - Denning, M F AU - Morasso, M I AD - Laboratory of Skin Biology, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/05/04/ PY - 2001 DA - 2001 May 04 SP - 60 EP - 65 VL - 496 IS - 1 SN - 0014-5793, 0014-5793 KW - Distal-less homeobox proteins KW - 0 KW - Enzyme Inhibitors KW - Homeodomain Proteins KW - Indoles KW - Isoenzymes KW - Maleimides KW - Peptide Fragments KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Index Medicus KW - Animals KW - DNA -- metabolism KW - Cell Nucleus -- chemistry KW - Peptide Fragments -- analysis KW - Cell Differentiation KW - Mice KW - Amino Acid Sequence KW - Precipitin Tests KW - Mice, Inbred BALB C KW - Binding Sites -- physiology KW - Isoenzymes -- metabolism KW - Mutagenesis, Site-Directed KW - Animals, Newborn KW - Phosphorylation KW - Cells, Cultured KW - Molecular Sequence Data KW - Keratinocytes -- cytology KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Keratinocytes -- metabolism KW - Indoles -- pharmacology KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Homeodomain Proteins -- genetics KW - Transcription Factors -- metabolism KW - Transcription Factors -- chemistry KW - Homeodomain Proteins -- metabolism KW - Transcription Factors -- genetics KW - Homeodomain Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70833571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Phosphorylation+of+murine+homeodomain+protein+Dlx3+by+protein+kinase+C.&rft.au=Park%2C+G+T%3BDenning%2C+M+F%3BMorasso%2C+M+I&rft.aulast=Park&rft.aufirst=G&rft.date=2001-05-04&rft.volume=496&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1996 Dec;135(6 Pt 2):1879-87 [8991098] J Biol Chem. 1997 Jan 10;272(2):952-60 [8995387] Cell Growth Differ. 1995 Feb;6(2):149-57 [7756173] Curr Opin Genet Dev. 1994 Oct;4(5):725-36 [7531523] J Biol Chem. 1996 Oct 4;271(40):24862-8 [8798762] J Invest Dermatol. 1996 Mar;106(3):482-9 [8648181] Mol Carcinog. 1997 Jan;18(1):44-53 [9022812] Hum Mol Genet. 1998 Mar;7(3):563-9 [9467018] J Cell Sci. 1998 Jul;111 ( Pt 13):1823-30 [9625745] Mol Cell Biol. 1998 Sep;18(9):5199-207 [9710604] Mol Cell Biol. 1999 Jan;19(1):526-36 [9858576] Nucleic Acids Res. 1999 Feb 1;27(3):764-70 [9889271] J Biol Chem. 1999 Sep 10;274(37):26599-608 [10473625] FASEB J. 1999 Oct;13(13):1658-76 [10506570] J Biol Chem. 2000 Jan 21;275(3):1601-7 [10636851] J Cell Sci. 2000 Nov;113 ( Pt 22):4013-23 [11058088] Nature. 1989 Mar 30;338(6214):432-4 [2564639] J Cell Biol. 1989 Sep;109(3):1207-17 [2475508] J Cell Physiol. 1989 Nov;141(2):235-42 [2808535] Nucleic Acids Res. 1991 May 11;19(9):2499 [2041787] Mol Carcinog. 1992;5(4):286-92 [1379814] J Cell Biol. 1993 Jan;120(1):217-25 [7678013] Adv Second Messenger Phosphoprotein Res. 1993;28:261-9 [8398412] Dev Biol. 1994 Mar;162(1):267-76 [7907299] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway. AN - 70825302; 11278694 AB - In this study, we focus on different modes of regulation of STRA13, a human ortholog of the mouse basic helix-loop-helix transcriptional factor, previously identified by us as a new von Hippel-Lindau tumor suppressor gene (VHL) target. The gene was overexpressed in VHL-deficient cell lines and tumors, specifically clear cell renal carcinomas and hemangioblastomas. Introduction of wild type VHL transgene into clear cell renal carcinoma restored low level expression of STRA13. Overexpression was also detected in many common malignancies with an intact VHL gene, suggesting the existence of another, VHL-independent pathway of STRA13 regulation. Similar to many other von Hippel-Lindau tumor-suppressor protein (pVHL) targets, the expression of STRA13 on the mRNA level was hypoxia-sensitive, indicating oxygen-dependent regulation of the gene, presumably through the pVHL/hypoxia-inducible factor 1 (HIF-1) pathway. The yeast two-hybrid screening revealed interaction of the STRA13 protein with the human ubiquitin-conjugating enzyme (UBC9) protein, the specificity of which was confirmed in mammalian cells. By adding the proteasome inhibitor acetyl-leucinyl-leucinyl-norleucinal, we demonstrated that the 26 S proteasome pathway regulates the stability of pSTRA13. Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. Hypoxia treatment of mammalian cells transiently expressing STRA13 protein showed that stability of pSTRA13 is not affected by hypoxia or VHL. Thus, STRA13, a new pVHL target, is regulated in cells on multiple levels. We propose that STRA13 may play a critical role in carcinogenesis, since it is a potent transcriptional regulator, abundant in a variety of common tumors. JF - The Journal of biological chemistry AU - Ivanova, A V AU - Ivanov, S V AU - Danilkovitch-Miagkova, A AU - Lerman, M I AD - Laboratory of Immunobiology, NCI-Frederick Cancer Research Development Center, Frederick, Maryland 21702, USA. ivanova@mail.ncifcrf.gov Y1 - 2001/05/04/ PY - 2001 DA - 2001 May 04 SP - 15306 EP - 15315 VL - 276 IS - 18 SN - 0021-9258, 0021-9258 KW - BHLHE40 protein, human KW - 0 KW - Basic Helix-Loop-Helix Transcription Factors KW - Bhlhe40 protein, mouse KW - Homeodomain Proteins KW - Multienzyme Complexes KW - Proteins KW - Tumor Suppressor Proteins KW - Ubiquitin-Conjugating Enzymes KW - EC 2.3.2.23 KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - ubiquitin-conjugating enzyme UBC9 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Subcellular Fractions -- metabolism KW - Protein Binding KW - Hydrolysis KW - Cell Line KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- pathology KW - Multienzyme Complexes -- metabolism KW - Genes, Tumor Suppressor KW - Cell Hypoxia KW - Proteins -- genetics KW - Proteins -- physiology KW - Homeodomain Proteins -- chemistry KW - Ligases -- physiology KW - Gene Expression Regulation -- physiology KW - Homeodomain Proteins -- genetics KW - Cysteine Endopeptidases -- metabolism KW - Homeodomain Proteins -- metabolism KW - Ligases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70825302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+STRA13+by+the+von+Hippel-Lindau+tumor+suppressor+protein%2C+hypoxia%2C+and+the+UBC9%2Fubiquitin+proteasome+degradation+pathway.&rft.au=Ivanova%2C+A+V%3BIvanov%2C+S+V%3BDanilkovitch-Miagkova%2C+A%3BLerman%2C+M+I&rft.aulast=Ivanova&rft.aufirst=A&rft.date=2001-05-04&rft.volume=276&rft.issue=18&rft.spage=15306&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a powerful high affinity antagonist that inhibits biological activities of human interleukin-13. AN - 70811354; 11278629 AB - Interleukin-13 (IL-13), a predominantly Th2-derived cytokine, appears to play a central pathological role in asthma, atopic dermatitis, allergic rhinitis, some parasitic infections, and cancer. We hypothesized that an IL-13 antagonist may have profound therapeutic utility in these conditions. We, therefore, mutagenized human IL-13 in which Glu at position 13 was substituted by a Lys residue. This highly purified recombinant IL-13 variant, IL-13E13K, bound with 4-fold higher affinity to the IL-13 receptor than wild-type IL-13 but retained no detectable proliferative activity on the TF-1 hematopoietic cell line. IL-13E13K competitively inhibited IL-13- and IL-4-dependent TF-1 proliferation. It also inhibited IL-13-induced STAT-6 (signal transduction and activator of transducer-6) activation in immune cells and cancer cells and reversed IL-13-induced inhibition of CD14 expression on human primary monocytes. These results demonstrate that high affinity binding and signal generation can be uncoupled efficiently in a ligand receptor interaction. These results also suggest that IL-13E13K may be a useful antagonist for the treatment of allergic, inflammatory, and parasitic diseases or even malignancies in which IL-13 plays a central role. JF - The Journal of biological chemistry AU - Oshima, Y AU - Puri, R K AD - Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/05/04/ PY - 2001 DA - 2001 May 04 SP - 15185 EP - 15191 VL - 276 IS - 18 SN - 0021-9258, 0021-9258 KW - Antigens, CD14 KW - 0 KW - Interleukin-13 KW - Interleukin-5 KW - Interleukin-4 KW - 207137-56-2 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Interleukin-5 -- chemistry KW - Models, Molecular KW - Humans KW - Cell Division -- drug effects KW - Amino Acid Sequence KW - Granulocyte-Macrophage Colony-Stimulating Factor -- chemistry KW - Antigens, CD14 -- metabolism KW - Molecular Sequence Data KW - Cytotoxicity, Immunologic -- drug effects KW - Sequence Homology, Amino Acid KW - Down-Regulation -- drug effects KW - Interleukin-4 -- chemistry KW - Cell Line KW - Protein Conformation KW - Interleukin-13 -- chemistry KW - Interleukin-13 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70811354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+a+powerful+high+affinity+antagonist+that+inhibits+biological+activities+of+human+interleukin-13.&rft.au=Oshima%2C+Y%3BPuri%2C+R+K&rft.aulast=Oshima&rft.aufirst=Y&rft.date=2001-05-04&rft.volume=276&rft.issue=18&rft.spage=15185&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In situ detection of unexpected patterns of mutant p53 gene expression in non-small cell lung cancers. AN - 70937939; 11420668 AB - Many solid tumors, including non-small cell lung cancers (NSCLCs), are characterized by heterogenous expression of p53 protein in the neoplastic cells. To analyse the molecular implications of this finding, we examined topographic distribution of p53 mutations using in situ polymerase chain reaction (PCR) in primary NSCLCs, showing distinct patterns of variable p53 overexpression by immunohistochemistry. Unique sets of primers for each mutation were designed, and optimal PCR conditions were determined by standard PCR using DNA from cloned mutants or cell lines established from these tumors. All tumor cell nuclei, regardless of the status of p53 overexpression, demonstrated homogeneous distribution of mutant p53 with specific primers, indicating that only subgroups of the mutated cells overexpressed p53 protein. In situ reverse transcription (RT)-PCR was applied to detect mutant mRNA in the individual tumor cells using specific primers. We found that in each case the distribution of mutant p53 mRNA coincided with that of immunohistochemical overexpression of p53 protein. Our results suggest that the regulation of mutant p53 expression, but not the genotype, is heterogeneous in the neoplastic cells. The topographic genomapping of p53 in NSCLC using in situ PCR provides a novel approach to view molecular mechanisms of lung carcinogenesis. JF - Oncogene AU - Ebina, M AU - Martínez, A AU - Birrer, M J AU - Ilona Linnoila, R AD - Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institute of Health, USA. Y1 - 2001/05/03/ PY - 2001 DA - 2001 May 03 SP - 2579 EP - 2586 VL - 20 IS - 20 SN - 0950-9232, 0950-9232 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Humans KW - Aged KW - Middle Aged KW - Tumor Suppressor Protein p53 -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction KW - Immunohistochemistry KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Genes, p53 -- genetics KW - Point Mutation KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70937939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=In+situ+detection+of+unexpected+patterns+of+mutant+p53+gene+expression+in+non-small+cell+lung+cancers.&rft.au=Ebina%2C+M%3BMart%C3%ADnez%2C+A%3BBirrer%2C+M+J%3BIlona+Linnoila%2C+R&rft.aulast=Ebina&rft.aufirst=M&rft.date=2001-05-03&rft.volume=20&rft.issue=20&rft.spage=2579&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - NIGMS support programs for structural genomics AN - 39339047; 3584996 AU - Edmonds, C G Y1 - 2001/05/03/ PY - 2001 DA - 2001 May 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39339047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=NIGMS+support+programs+for+structural+genomics&rft.au=Edmonds%2C+C+G&rft.aulast=Edmonds&rft.aufirst=C&rft.date=2001-05-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cambridge Healthtech Institute, 1037 Chestnut Street, Newton Upper Falls, MA 02464, USA; URL: www.healthtech.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Peptide mapping by CE: How close is theoretical simulation to experimental determination AN - 39290559; 3585617 AU - Issaq, HJ AU - Janini, G M AU - Metral, C AU - Muschik, G M Y1 - 2001/05/03/ PY - 2001 DA - 2001 May 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39290559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Peptide+mapping+by+CE%3A+How+close+is+theoretical+simulation+to+experimental+determination&rft.au=Issaq%2C+HJ%3BJanini%2C+G+M%3BMetral%2C+C%3BMuschik%2C+G+M&rft.aulast=Issaq&rft.aufirst=HJ&rft.date=2001-05-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: California Separation Society, 156 South Spruce Avenue, Suite 207A, South San Francisco, CA 94080-4556, USA; phone: 650-876-0792; fax: 650-876-0793; URL: www.casss.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - FGF receptor mutant mice as tools for mechanistic and therapeutic studies for human skeletal dysplasias AN - 39284380; 3588656 AU - Deng, C-X Y1 - 2001/05/03/ PY - 2001 DA - 2001 May 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39284380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=FGF+receptor+mutant+mice+as+tools+for+mechanistic+and+therapeutic+studies+for+human+skeletal+dysplasias&rft.au=Deng%2C+C-X&rft.aulast=Deng&rft.aufirst=C-X&rft.date=2001-05-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cambridge Healthtech Institute, 1037 Chestnut Street, Newton Upper Falls, MA 02464, USA; URL: www.healthtech.com N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica AN - 954576618; 13758341 AB - We examined factors associated with high-grade squamous intraepithelial lesions (HSIL) and cervical cancer among human papillomavirus (HPV)-infected women in a prevalent case-control study conducted within a population-based cohort of 10[puncsp]077 women in Costa Rica. We compared 146 women with HPV-positive HSIL or cancer (HSIL/CA) against 843 HPV-positive women without evidence of HSIL/CA. Subjects completed a risk factor questionnaire. We evaluated the associations between exposures and HSIL/CA among women positive for any HPV and restricted to those positive for high-risk HPV types. Risk of HSIL/CA increased with increasing number of live births (P sub(trend)= 0.04). Women who smoked 6+ cigarettes/day had a RR for HSIL/CA of 2.7 (95% CI = 1.1-6.7) compared to non-smokers. Current use of barrier contraceptives was associated with a reduction in risk of HSIL/CA (RR = 0.39; 95% CI = 0.16-0.96). Sexual behaviour and a self-reported history of sexually transmitted diseases (STDs) other than HPV were not associated with HSIL/CA. Oral contraceptive use was associated with HSIL/CA among women with <3 pregnancies. Effects were similar in analysis restricted to women positive for high-risk HPV types. Among women positive for high-risk HPV types, 44% of HSIL/CA could be attributed to multiparity (.3 pregnancies) and/or smoking. Among HPV-positive women, multiparity and smoking are risk factors for HSIL/CA. Oral contraceptive use may be associated with HSIL/CA in subgroups of women. [copy 2001 Cancer Research Campaignhttp://www.bjcancer.com JF - British Journal of Cancer AU - Hildesheim, A AU - Herrero, R AU - Castle, P E AU - Wacholder, S AU - Bratti, M C AU - Sherman, M E AU - Lorincz, A T AU - Burk, R D AU - Morales, J AU - Rodriguez, A C AU - Helgesen, K AU - Alfaro, M AU - Hutchinson, M AU - Balmaceda, I AU - Greenberg, M AU - Schiffman, M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1219 EP - 1226 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 84 IS - 9 SN - 0007-0920, 0007-0920 KW - Virology & AIDS Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Cancer KW - Cervical cancer KW - Cigarettes KW - Contraceptives KW - Contraceptives (oral) KW - Historical account KW - Inventories KW - Lesions KW - Population studies KW - Pregnancy KW - Risk factors KW - Risk groups KW - Sexual behavior KW - Sexually-transmitted diseases KW - Smoking KW - contraceptives KW - sexual behavior KW - sexually transmitted diseases KW - Costa Rica KW - Human papillomavirus KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs KW - V 22370:Oncology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954576618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=HPV+co-factors+related+to+the+development+of+cervical+cancer%3A+results+from+a+population-based+study+in+Costa+Rica&rft.au=Hildesheim%2C+A%3BHerrero%2C+R%3BCastle%2C+P+E%3BWacholder%2C+S%3BBratti%2C+M+C%3BSherman%2C+M+E%3BLorincz%2C+A+T%3BBurk%2C+R+D%3BMorales%2C+J%3BRodriguez%2C+A+C%3BHelgesen%2C+K%3BAlfaro%2C+M%3BHutchinson%2C+M%3BBalmaceda%2C+I%3BGreenberg%2C+M%3BSchiffman%2C+M&rft.aulast=Hildesheim&rft.aufirst=A&rft.date=2001-05-01&rft.volume=84&rft.issue=9&rft.spage=1219&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1054%2Fbjoc.2001.1779 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2013-01-11 N1 - SubjectsTermNotLitGenreText - Inventories; Smoking; Sexually-transmitted diseases; Cigarettes; Risk factors; Cervical cancer; Population studies; Risk groups; Contraceptives (oral); Sexual behavior; Contraceptives; Pregnancy; Historical account; sexual behavior; Lesions; sexually transmitted diseases; Cancer; contraceptives; Human papillomavirus; Costa Rica DO - http://dx.doi.org/10.1054/bjoc.2001.1779 ER - TY - JOUR T1 - Searching for array standards in Rockville AN - 864949647; 13695251 JF - Nature Biotechnology AU - Star, Robert A AU - Rasooly, Rebekah S AD - Robert A. Star is senior scientific advisor and chief, renal diagnostics and therapeutics, Division of Kidney, Urologic, and Hematologic Diseases, NIDDK/NIH, and Rebekah S. Rasooly is program director, cell biology & genetics at the Division of Neuroscience & Behavioral Research, National Institute on Drug Abuse/NIH, Bethesda, MD 20892-9555(rrasooly[AT]nida.nih.gov). Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 418 EP - 419 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 19 IS - 5 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864949647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Searching+for+array+standards+in+Rockville&rft.au=Star%2C+Robert+A%3BRasooly%2C+Rebekah+S&rft.aulast=Star&rft.aufirst=Robert&rft.date=2001-05-01&rft.volume=19&rft.issue=5&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F88070 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2012-03-29 DO - http://dx.doi.org/10.1038/88070 ER - TY - JOUR T1 - Abnormally increased semantic priming in children with symptomatic HIV-1 disease: evidence for impaired development of semantics? AN - 85351092; pmid-11396551 AB - Language deficits are a major characteristic of neurobehavioral dysfunction in pediatric HIV disease. An object decision task, which assessed reaction time facilitation following a semantic or identical prime in comparison to an unrelated prime, was used to investigate whether semantic processing abnormalities could be responsible, in part, for these deficits. Thirty children with vertically acquired HIV infection (M age 9.0 years; range 6-13) participated. Either a picture of the same object (repetition prime), a semantically related object (semantic prime), a semantically unrelated object, or a nonsense object preceded a target picture, which in 50% of the cases was a real object. Brain scans of children were rated and used together with neurobehavioral functioning to classify children as having HIV-related CNS abnormalities (n = 13) or not (n = 17). Increased semantic priming but not repetition priming was associated with a greater degree of cortical atrophy. Furthermore, CNS compromised children had significantly faster reaction times following a semantic prime compared to an unrelated prime than non-compromised patients. This facilitation following semantic priming for the CNS compromised patients (13.3%) almost equaled the facilitation following repetition priming (15.3%) while for the non-compromised patients facilitation following semantic priming (7.9%) was clearly smaller than following repetition priming (14.6%). These data suggest that HIV infection in children may result in a reduced neural network leading to impoverished semantic representations characterized by poor differentiation between closely related objects. JF - Journal of the International Neuropsychological Society : JINS AU - Brouwers, P AU - van Engelen, M AU - Lalonde, F AU - Perez, L AU - de Haan, E AU - Wolters, P AU - Martin, A AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA. brouwers@bcm.tmc.edu Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 491 EP - 501 VL - 7 IS - 4 SN - 1355-6177, 1355-6177 KW - Index Medicus KW - National Library of Medicine KW - Acquired Immunodeficiency Syndrome: diagnosis KW - Acquired Immunodeficiency Syndrome: immunology KW - *Acquired Immunodeficiency Syndrome: virology KW - Antigens, CD4: immunology KW - Atrophy: pathology KW - Blotting, Southern KW - Brain: pathology KW - Brain: radiography KW - Child KW - Child, Preschool KW - Cognition Disorders: diagnosis KW - Cognition Disorders: epidemiology KW - Female KW - *HIV-1: isolation & purification KW - Humans KW - Language Disorders: diagnosis KW - *Language Disorders: etiology KW - Male KW - Neuropsychological Tests KW - Polymerase Chain Reaction KW - Reaction Time KW - *Semantics KW - Severity of Illness Index KW - Tomography, X-Ray Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85351092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.atitle=Abnormally+increased+semantic+priming+in+children+with+symptomatic+HIV-1+disease%3A+evidence+for+impaired+development+of+semantics%3F&rft.au=Brouwers%2C+P%3Bvan+Engelen%2C+M%3BLalonde%2C+F%3BPerez%2C+L%3Bde+Haan%2C+E%3BWolters%2C+P%3BMartin%2C+A&rft.aulast=Brouwers&rft.aufirst=P&rft.date=2001-05-01&rft.volume=7&rft.issue=4&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.issn=13556177&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - News from the National Institute on Deafness and Other Communication Disorders. AN - 85350043; pmid-11347628 JF - Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology AU - Battey, J F AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 287 EP - 290 VL - 22 IS - 3 SN - 1531-7129, 1531-7129 KW - Index Medicus KW - National Library of Medicine KW - Clinical Trials as Topic KW - Cochlear Implantation KW - Communication Disorders: diagnosis KW - *Communication Disorders: epidemiology KW - Deafness: surgery KW - Ear, Inner: physiopathology KW - *Hearing Disorders: epidemiology KW - Hearing Disorders: etiology KW - Hearing Disorders: physiopathology KW - Humans KW - Infant, Newborn KW - *Neonatal Screening KW - Neurofibromatosis 2: complications KW - Otitis Media: complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85350043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.atitle=News+from+the+National+Institute+on+Deafness+and+Other+Communication+Disorders.&rft.au=Battey%2C+J+F&rft.aulast=Battey&rft.aufirst=J&rft.date=2001-05-01&rft.volume=22&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.issn=15317129&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Assessment of posterior cricoarytenoid botulinum toxin injections in patients with abductor spasmodic dysphonia. AN - 85347113; pmid-11372922 AB - In this study, we compared 2 techniques for injection of botulinum toxin type A (Botox) into the posterior cricoarytenoid (PCA) muscle for the treatment of abductor spasmodic dysphonia (ABSD). Fifteen patients with ABSD were enrolled in a prospective randomized crossover treatment trial comparing the 2 injection techniques. The PCA muscle was injected with 5 units on each side, with the injections staged 2 weeks apart, via either a percutaneous posterior-lateral approach or a transnasal fiberoptic approach. Eleven patients reported some benefit with the injections; however, the patient-perceived benefits were not related to changes in symptoms on blinded counts by speech pathologists. No significant reductions in the numbers of breathy breaks occurred with either technique, and no differences were found between techniques. Although patients perceived a benefit, blinded symptom counts did not substantiate these benefits. Thus, PCA muscle injections of Botox provided limited benefits to patients with ABSD, demonstrating the need for a more effective therapy for these patients. JF - The Annals of otology, rhinology, and laryngology AU - Bielamowicz, S AU - Squire, S AU - Bidus, K AU - Ludlow, C L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 406 EP - 412 VL - 110 IS - 5 Pt 1 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Adult KW - Aged KW - *Botulinum Toxins, Type A: administration & dosage KW - Chi-Square Distribution KW - Electromyography KW - Female KW - Humans KW - Injections, Intramuscular: methods KW - Male KW - Middle Aged KW - *Neuromuscular Agents: administration & dosage KW - Treatment Outcome KW - *Voice Disorders: drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85347113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Assessment+of+posterior+cricoarytenoid+botulinum+toxin+injections+in+patients+with+abductor+spasmodic+dysphonia.&rft.au=Bielamowicz%2C+S%3BSquire%2C+S%3BBidus%2C+K%3BLudlow%2C+C+L&rft.aulast=Bielamowicz&rft.aufirst=S&rft.date=2001-05-01&rft.volume=110&rft.issue=5+Pt+1&rft.spage=406&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study. AN - 77077205; 11313108 AB - Animal studies have shown that dietary intake of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), causes increased levels of tumors at several sites, particularly in the upper gastrointestinal tract. However, the role of dietary intake of BaP and cancer in humans is not clear. We created a BaP database of selected food products that could be linked to Food Frequency Questionnaires (FFQs) to estimate BaP intake. BaP levels were measured for each food line-item (composite samples) which consisted of a variety of foods in a FFQ. Composite sample parts were derived from the Second National Health and Nutrition Examination Survey (NHANES II) which represents the most common food items consumed by the general population. Meat samples were cooked by different techniques in controlled conditions, and by various restaurants and fast-food chains. Non-meat products were purchased from the major national supermarket chains. The quantities of BaP were measured using a thin-layer chromatography (TLC)/spectrofluorometer technique and were highly correlated with both BaP (r=0.99) [corrected] and sum of carcinogenic PAH (r=0.98) measured by HPLC technique. We linked our database to the results from a FFQ and estimated the daily BaP intake of various food items in 228 subjects in the Washington, DC metropolitan area. The highest levels of BaP (up to about 4 ng BaP/g of cooked meat) were found in grilled/barbecued very well done steaks and hamburgers and in grilled/barbecued well done chicken with skin. BaP concentrations were lower in meats that were grilled/barbecued to medium done and in all broiled or pan-fried meat samples regardless of doneness level. The BaP levels in non-meat items were generally low. However, certain cereals and greens (e.g. kale, collard greens) had levels up to 0.5 ng/g. In our population, the bread/cereal/grain, and grilled/barbecued meat, respectively, contributed 29 and 21 percent to the mean daily intake of BaP. This database may be helpful in initial attempts to assess dietary BaP exposures in studies of cancer etiology. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Kazerouni, N AU - Sinha, R AU - Hsu, C H AU - Greenberg, A AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. kazeroun@exchange.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 423 EP - 436 VL - 39 IS - 5 SN - 0278-6915, 0278-6915 KW - Carcinogens KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Index Medicus KW - Swine KW - Animals KW - Vegetables -- chemistry KW - Cattle KW - Food Preferences KW - Databases as Topic KW - Cooking KW - Surveys and Questionnaires KW - Seafood -- analysis KW - Meat -- analysis KW - Edible Grain -- chemistry KW - Benzo(a)pyrene -- administration & dosage KW - Benzo(a)pyrene -- analysis KW - Food Contamination -- analysis KW - Carcinogens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77077205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Analysis+of+200+food+items+for+benzo%5Ba%5Dpyrene+and+estimation+of+its+intake+in+an+epidemiologic+study.&rft.au=Kazerouni%2C+N%3BSinha%2C+R%3BHsu%2C+C+H%3BGreenberg%2C+A%3BRothman%2C+N&rft.aulast=Kazerouni&rft.aufirst=N&rft.date=2001-05-01&rft.volume=39&rft.issue=5&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Food Chem Toxicol 2002 Jan;40(1):133 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. AN - 77074629; 11312651 AB - There is strong evidence from epidemiologic studies of an association between chronic exposure to inorganic arsenic (iAs) and hyperpigmentation, hyperkeratosis, and neoplasia in the skin. Although it is generally accepted that methylation is a mechanism of arsenic detoxification, recent studies have suggested that methylated arsenicals also have deleterious biological effects. In these studies we compare the effects of inorganic arsenicals (arsenite (iAs(III)) and arsenate (iAs(V))) and trivalent and pentavalent methylated arsenicals (methylarsine oxide (MAs(III)O), complex of dimethylarsinous acid with glutathione (DMAs(III)GS), methylarsonic acid (MAs(V)), and dimethylarsinic acid (DMAs(V))) in human keratinocyte cultures. Viability testing showed that the relative toxicities of the arsenicals were as follows: iAs(III) > MAs(III)O > DMAs(III)GS > DMAs(V) > MAs(V) > iAs(V). Trivalent arsenicals induced an increase in cell proliferation at concentrations in the 0.001 to 0.01 microM range, while at high concentrations (>0.5 microM) cell proliferation was inhibited. Pentavalent arsenicals did not stimulate cell proliferation. As seen in the viability studies, the methylated forms of As(V) were more cytotoxic than iAs(V). Exposure to low doses of trivalent arsenicals stimulated secretion of the growth-promoting cytokines, granulocyte macrophage colony stimulating factor and tumor necrosis factor-alpha. DMAs(V) reduced cytokine secretion at concentrations at which proliferation and viability were not affected. These data suggest that methylated arsenicals, products of the metabolic conversion of inorganic arsenic, can significantly affect viability and proliferation of human keratinocytes and modify their secretion of inflammatory and growth-promoting cytokines. Copyright 2001 Academic Press. JF - Toxicology and applied pharmacology AU - Vega, L AU - Styblo, M AU - Patterson, R AU - Cullen, W AU - Wang, C AU - Germolec, D AD - Laboratory of Toxicology and Environmental Immunology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. Y1 - 2001/05/01/ PY - 2001 DA - 2001 May 01 SP - 225 EP - 232 VL - 172 IS - 3 SN - 0041-008X, 0041-008X KW - Arsenates KW - 0 KW - Arsenicals KW - Arsenites KW - Cytokines KW - Interleukin-6 KW - Tumor Necrosis Factor-alpha KW - methylarsine oxide KW - 593-58-8 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cacodylic Acid KW - AJ2HL7EU8K KW - Glutathione KW - GAN16C9B8O KW - monomethylarsonic acid KW - J37VJ5709S KW - arsenite KW - N5509X556J KW - arsenic acid KW - N7CIZ75ZPN KW - Index Medicus KW - Arsenites -- pharmacology KW - Arsenates -- pharmacology KW - Interleukin-6 -- secretion KW - Humans KW - Arsenites -- toxicity KW - Glutathione -- pharmacology KW - Tumor Necrosis Factor-alpha -- secretion KW - Structure-Activity Relationship KW - Cell Survival -- drug effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- secretion KW - Adult KW - Arsenates -- toxicity KW - Enzyme-Linked Immunosorbent Assay KW - Cacodylic Acid -- toxicity KW - Methylation KW - Cacodylic Acid -- pharmacology KW - Cell Line KW - Female KW - Keratinocytes -- physiology KW - Arsenicals -- chemistry KW - Cytokines -- secretion KW - Cell Division -- drug effects KW - Keratinocytes -- cytology KW - Arsenicals -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77074629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Differential+effects+of+trivalent+and+pentavalent+arsenicals+on+cell+proliferation+and+cytokine+secretion+in+normal+human+epidermal+keratinocytes.&rft.au=Vega%2C+L%3BStyblo%2C+M%3BPatterson%2C+R%3BCullen%2C+W%3BWang%2C+C%3BGermolec%2C+D&rft.aulast=Vega&rft.aufirst=L&rft.date=2001-05-01&rft.volume=172&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis. AN - 77073538; 11313413 AB - B10.Q mice are normally susceptible to the induction of collagen-induced arthritis. We noted that one subline of B10.Q mice, B10.Q/J, was completely resistant to disease induction when immunized with collagen in CFA. B10.Q/J mice have a global defect in the generation of Th1 responses, and Ag-specific T cells derived from this strain failed to produce IFN-gamma. Because T cells from these mice could produce normal amounts of IFN-gamma when activated by IL-12/IL-18-independent stimuli, the defect appeared to be a failure to respond to IL-12. This defect extended to NK cells, which also failed to produce IFN-gamma when stimulated by IL-12. The capacity of NK cells, but not activated T cells, to produce IFN-gamma in response to IL-12 could be partially restored by IL-18. The expression of the IL-12R beta1- and beta2-chains on T cells and NK cells from B10.Q/J mice was normal. However, activated T cells from B10.Q/J mice did not signal normally through the IL-12R and manifested a defect in their capacity to phosphorylate Stat4. This defect was partial in that it could be overcome by increasing both the concentration of IL-12 and the incubation times in the Stat4 phosphorylation assays. Because Stat4 function is apparently intact in B10.Q/J mice, the defect in IL-12 signaling can be localized between the IL-12R complex and Stat4. This subtle abnormality in IL-12 responsiveness results in a profound defect in the generation of Th1 cells and the development of autoimmune disease. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ortmann, R AU - Smeltz, R AU - Yap, G AU - Sher, A AU - Shevach, E M AD - Laboratories of. Immunology and Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/05/01/ PY - 2001 DA - 2001 May 01 SP - 5712 EP - 5719 VL - 166 IS - 9 SN - 0022-1767, 0022-1767 KW - DNA-Binding Proteins KW - 0 KW - H-2 Antigens KW - Il12rb1 protein, mouse KW - Il12rb2 protein, mouse KW - Interleukin-18 KW - Receptors, Interleukin KW - Receptors, Interleukin-12 KW - STAT4 Transcription Factor KW - Stat4 protein, mouse KW - Trans-Activators KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - CD4-Positive T-Lymphocytes -- immunology KW - Th1 Cells -- metabolism KW - Receptors, Interleukin -- biosynthesis KW - Lymphocyte Activation -- genetics KW - Phosphorylation KW - Spleen -- immunology KW - Receptors, Interleukin -- physiology KW - Drug Synergism KW - Male KW - DNA-Binding Proteins -- metabolism KW - Th1 Cells -- immunology KW - Interferon-gamma -- genetics KW - Interleukin-18 -- pharmacology KW - Spleen -- cytology KW - Interferon-gamma -- biosynthesis KW - Mice KW - H-2 Antigens -- genetics KW - CD4-Positive T-Lymphocytes -- metabolism KW - Interferon-gamma -- deficiency KW - Cells, Cultured KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology KW - Mice, Inbred C57BL -- genetics KW - Interleukin-12 -- metabolism KW - Interleukin-12 -- physiology KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - Interleukin-12 -- deficiency KW - Genetic Predisposition to Disease KW - Interleukin-12 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77073538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=A+heritable+defect+in+IL-12+signaling+in+B10.Q%2FJ+mice.+I.+In+vitro+analysis.&rft.au=Ortmann%2C+R%3BSmeltz%2C+R%3BYap%2C+G%3BSher%2C+A%3BShevach%2C+E+M&rft.aulast=Ortmann&rft.aufirst=R&rft.date=2001-05-01&rft.volume=166&rft.issue=9&rft.spage=5712&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ZAP-70 and SLP-76 regulate protein kinase C-theta and NF-kappa B activation in response to engagement of CD3 and CD28. AN - 77073088; 11313406 AB - The transcription factor NF-kappaB is a critical regulator of T cell function that becomes strongly activated in response to coengagement of TCR and CD28. Although events immediately proximal to NF-kappaB activation are well understood, uncertainty remains over which upstream signaling pathways engaged by TCR and CD28 lead to NF-kappaB activation. By using Jurkat T cell lines that are deficient or replete for either the protein tyrosine kinase ZAP-70 or the cytosolic adapter molecule SLP-76, the role of these proteins in modulating NF-kappaB activation was examined. NF-kappaB was not activated in response to coengagement of TCR and CD28 in either the ZAP-70- or SLP-76-negative cells, whereas stimuli that bypass these receptors (PMA plus A23187, or TNF-alpha) activated NF-kappaB normally. Protein kinase C (PKC) theta activation, which is required for NF-kappaB activation, also was defective in these cells. Reexpression of ZAP-70 restored PKCtheta and NF-kappaB activation in response to TCR and CD28 coengagement. p95(vav) (Vav)-1 tyrosine phosphorylation was largely unperturbed in the ZAP-70-negative cells; however, receptor-stimulated SLP-76/Vav-1 coassociation was greatly reduced. Wild-type SLP-76 fully restored PKCtheta and NF-kappaB activation in the SLP-76-negative cells, whereas 3YF-SLP-76, which lacks the sites of tyrosine phosphorylation required for Vav-1 binding, only partially rescued signaling. These data illustrate the importance of the ZAP-70/SLP-76 signaling pathway in CD3/CD28-stimulated activation of PKC theta and NF-kappaB, and suggest that Vav-1 association with SLP-76 may be important in this pathway. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Herndon, T M AU - Shan, X C AU - Tsokos, G C AU - Wange, R L AD - Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2001/05/01/ PY - 2001 DA - 2001 May 01 SP - 5654 EP - 5664 VL - 166 IS - 9 SN - 0022-1767, 0022-1767 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Antigens, CD28 KW - Antigens, CD3 KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - I-kappa B Proteins KW - Ionophores KW - Isoenzymes KW - NF-kappa B KW - NFKBIA protein, human KW - Phosphoproteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-vav KW - Receptors, Antigen, T-Cell KW - SLP-76 signal Transducing adaptor proteins KW - VAV1 protein, human KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - PRKCQ protein, human KW - 148374-93-0 KW - Calcimycin KW - 37H9VM9WZL KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - ZAP-70 Protein-Tyrosine Kinase KW - EC 2.7.10.2 KW - ZAP70 protein, human KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Jurkat Cells KW - Proto-Oncogene Proteins -- metabolism KW - Calcimycin -- pharmacology KW - T-Lymphocytes -- enzymology KW - Receptors, Antigen, T-Cell -- physiology KW - Lymphocyte Activation -- drug effects KW - T-Lymphocytes -- metabolism KW - Lymphocyte Activation -- genetics KW - Ionophores -- pharmacology KW - Kinetics KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Tyrosine -- metabolism KW - T-Lymphocytes -- drug effects KW - Enzyme Activation -- immunology KW - DNA-Binding Proteins -- metabolism KW - Phosphoproteins -- genetics KW - Antigens, CD3 -- metabolism KW - Phosphoproteins -- physiology KW - Protein-Tyrosine Kinases -- metabolism KW - Isoenzymes -- metabolism KW - Protein Kinase C -- metabolism KW - Antigens, CD3 -- immunology KW - Phosphoproteins -- deficiency KW - Protein-Tyrosine Kinases -- genetics KW - Protein-Tyrosine Kinases -- biosynthesis KW - Protein-Tyrosine Kinases -- physiology KW - Antigens, CD28 -- immunology KW - Antigens, CD28 -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77073088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=ZAP-70+and+SLP-76+regulate+protein+kinase+C-theta+and+NF-kappa+B+activation+in+response+to+engagement+of+CD3+and+CD28.&rft.au=Herndon%2C+T+M%3BShan%2C+X+C%3BTsokos%2C+G+C%3BWange%2C+R+L&rft.aulast=Herndon&rft.aufirst=T&rft.date=2001-05-01&rft.volume=166&rft.issue=9&rft.spage=5654&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A heritable defect in IL-12 signaling in B10.Q/J mice. II. Effect on acute resistance to Toxoplasma gondii and rescue by IL-18 treatment. AN - 77072472; 11313414 AB - This study documents a defect in IL-12-dependent IFN-gamma responses in a substrain (B10.Q-H2-(q)/SgJ) of B10.Q mice that manifests as an acute susceptibility to infection by the intracellular protozoan pathogen, Toxoplasma gondii. Despite robust systemic production of IL-12, infected B10.Q/J animals fail to mount an early IFN-gamma response after parasite inoculation. Genetic experiments revealed that the host resistance and IFN-gamma production defects are determined by a single autosomal recessive locus distinct from the Stat4 gene. Nonetheless, a delayed IL-12-mediated IFN-gamma response emerges in later stages of acute infection but is unable to prevent host mortality. IL-18 administration restores, in an IL-12-dependent manner, the early IFN-gamma response and host resistance of B10.Q/J animals. These in vivo studies indicate that the partially impaired IL-12 responsiveness in B10.Q/J mice can result in defective host resistance and demonstrate a therapeutic function for IL-18 in reversing a genetically based immunodeficiency in IL-12-dependent IFN-gamma production. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Yap, G S AU - Ortmann, R AU - Shevach, E AU - Sher, A AD - Laboratories of. Parasitic Diseases and Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/05/01/ PY - 2001 DA - 2001 May 01 SP - 5720 EP - 5725 VL - 166 IS - 9 SN - 0022-1767, 0022-1767 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-18 KW - STAT4 Transcription Factor KW - Stat4 protein, mouse KW - Trans-Activators KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Injections, Intraperitoneal KW - Animals KW - Interferon-gamma -- genetics KW - DNA-Binding Proteins -- genetics KW - Interferon-gamma -- biosynthesis KW - Mice KW - Immunity, Innate KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Quantitative Trait, Heritable KW - Trans-Activators -- genetics KW - Cells, Cultured KW - Interferon-gamma -- deficiency KW - Crosses, Genetic KW - Drug Synergism KW - Male KW - Female KW - Genes, Recessive KW - Interleukin-18 -- administration & dosage KW - Toxoplasmosis, Animal -- genetics KW - Mice, Inbred C57BL -- genetics KW - Interleukin-18 -- therapeutic use KW - Interleukin-12 -- biosynthesis KW - Interleukin-12 -- physiology KW - Toxoplasmosis, Animal -- immunology KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - Interleukin-12 -- deficiency KW - Genetic Predisposition to Disease KW - Interleukin-12 -- genetics KW - Toxoplasmosis, Animal -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77072472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=A+heritable+defect+in+IL-12+signaling+in+B10.Q%2FJ+mice.+II.+Effect+on+acute+resistance+to+Toxoplasma+gondii+and+rescue+by+IL-18+treatment.&rft.au=Yap%2C+G+S%3BOrtmann%2C+R%3BShevach%2C+E%3BSher%2C+A&rft.aulast=Yap&rft.aufirst=G&rft.date=2001-05-01&rft.volume=166&rft.issue=9&rft.spage=5720&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient conversion of normal prion protein (PrP) by abnormal hamster PrP is determined by homology at amino acid residue 155. AN - 77072039; 11312338 AB - In the transmissible spongiform encephalopathies, disease is closely associated with the conversion of the normal proteinase K-sensitive host prion protein (PrP-sen) to the abnormal proteinase K-resistant form (PrP-res). Amino acid sequence homology between PrP-res and PrP-sen is important in the formation of new PrP-res and thus in the efficient transmission of infectivity across species barriers. It was previously shown that the generation of mouse PrP-res was strongly influenced by homology between PrP-sen and PrP-res at amino acid residue 138, a residue located in a region of loop structure common to PrP molecules from many different species. In order to determine if homology at residue 138 also affected the formation of PrP-res in a different animal species, we assayed the ability of hamster PrP-res to convert a panel of recombinant PrP-sen molecules to protease-resistant PrP in a cell-free conversion system. Homology at amino acid residue 138 was not critical for the formation of protease-resistant hamster PrP. Rather, homology between PrP-sen and hamster PrP-res at amino acid residue 155 determined the efficiency of formation of a protease-resistant product induced by hamster PrP-res. Structurally, residue 155 resides in a turn at the end of the first alpha helix in hamster PrP-sen; this feature is not present in mouse PrP-sen. Thus, our data suggest that PrP-res molecules isolated from scrapie-infected brains of different animal species have different PrP-sen structural requirements for the efficient formation of protease-resistant PrP. JF - Journal of virology AU - Priola, S A AU - Chabry, J AU - Chan, K AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. spriola@nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 4673 EP - 4680 VL - 75 IS - 10 SN - 0022-538X, 0022-538X KW - Amino Acids KW - 0 KW - Prions KW - Endopeptidase K KW - EC 3.4.21.64 KW - Index Medicus KW - Animals KW - Mice KW - Endopeptidase K -- metabolism KW - Cell Line KW - Mutagenesis KW - Cricetinae KW - Cell-Free System KW - Prions -- genetics KW - Prions -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77072039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Efficient+conversion+of+normal+prion+protein+%28PrP%29+by+abnormal+hamster+PrP+is+determined+by+homology+at+amino+acid+residue+155.&rft.au=Priola%2C+S+A%3BChabry%2C+J%3BChan%2C+K&rft.aulast=Priola&rft.aufirst=S&rft.date=2001-05-01&rft.volume=75&rft.issue=10&rft.spage=4673&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1994 Aug 11;370(6489):471-4 [7913989] J Virol. 1994 Aug;68(8):4873-8 [7913509] J Biol Chem. 1995 Feb 17;270(7):3299-305 [7852415] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3923-7 [7732006] Nature. 1995 Jun 22;375(6533):698-700 [7791905] J Virol. 1995 Dec;69(12):7754-8 [7494285] Nature. 1996 Jan 25;379(6563):339-43 [8552188] Lancet. 1996 Apr 6;347(9006):921-5 [8598754] Nature. 1996 Jul 11;382(6587):180-2 [8700211] J Gen Virol. 1996 Nov;77 ( Pt 11):2885-91 [8922485] Proc Natl Acad Sci U S A. 1997 May 13;94(10):4931-6 [9144167] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7281-5 [9207082] Nature. 1997 Jul 17;388(6639):285-8 [9230438] FEBS Lett. 1997 Aug 18;413(2):277-81 [9280297] Nature. 1997 Sep 4;389(6646):69-73 [9288968] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10069-74 [9294164] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13938-43 [9391131] Nature. 1998 Apr 23;392(6678):770 [9572135] Nat Med. 1998 Oct;4(10):1157-65 [9771749] J Biol Chem. 1998 Nov 27;273(48):32230-5 [9822701] Biomed Pharmacother. 1999;53(1):27-33 [10221165] Biochemistry. 1999 Apr 27;38(17):5362-77 [10220323] EMBO J. 1999 Jun 15;18(12):3193-203 [10369660] J Virol. 2000 Feb;74(3):1407-14 [10627551] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5836-41 [10811921] Mol Biotechnol. 1999 Nov;13(1):45-55 [10934521] Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10248-53 [10963685] EMBO J. 2000 Sep 1;19(17):4425-30 [10970836] J Wildl Dis. 1980 Jan;16(1):89-98 [7373730] Science. 1982 Apr 9;216(4542):136-44 [6801762] J Wildl Dis. 1982 Oct;18(4):465-71 [7154220] Cell. 1985 Apr;40(4):735-46 [2859120] Proc Natl Acad Sci U S A. 1986 Sep;83(17):6372-6 [3462700] EMBO J. 1986 Oct;5(10):2591-7 [3096712] J Gen Virol. 1987 May;68 ( Pt 5):1391-9 [3106566] Cell. 1987 Oct 23;51(2):229-40 [2444340] J Virol. 1987 Dec;61(12):3688-93 [2446004] J Gen Virol. 1988 Mar;69 ( Pt 3):711-6 [2895163] J Virol. 1988 Aug;62(8):2845-9 [2899175] J Virol. 1989 Jan;63(1):175-81 [2562814] Cell. 1989 Dec 1;59(5):847-57 [2574076] Cell. 1990 Nov 16;63(4):673-86 [1977523] J Virol. 1991 Jul;65(7):3667-75 [1710287] J Biol Chem. 1991 Sep 25;266(27):18217-23 [1680859] J Virol. 1991 Dec;65(12):6597-603 [1682507] Neurology. 1992 Jan;42(1):149-56 [1346470] J Virol. 1992 Jun;66(6):3271-7 [1374804] Cell. 1993 Jun 4;73(5):979-88 [8098995] Protein Sci. 1992 Aug;1(8):986-97 [1338978] Cell. 1993 Jul 2;73(7):1339-47 [8100741] Dev Biol Stand. 1993;80:131-40 [8270103] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9936-40 [7937921] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a novel posttranscriptional regulatory element by using a rev- and RRE-mutated human immunodeficiency virus type 1 DNA proviral clone as a molecular trap. AN - 77071912; 11312326 AB - Human immunodeficiency virus (HIV) and all other lentiviruses utilize the essential viral protein Rev, which binds to RRE RNA, to export their unspliced and partially spliced mRNAs from the nucleus. We used a rev- and RRE-defective HIV type 1 (HIV-1) molecular clone in complementation experiments to establish a method for the rapid isolation of posttranscriptional regulatory elements from the mammalian genome by selecting for rescue of virus replication. Viruses rescued by this method contained a novel element with homology to rodent intracisternal A-particle (IAP) retroelements. A functional element was contained within a 247-nucleotide fragment named RNA transport element (RTE), which was able to promote replication of the Rev- and RRE-defective HIV-1 in both human lymphoid cell lines and primary lymphocytes, demonstrating its potent posttranscriptional function. RTE was functional in many cell types, indicating that the cellular factors that recognize RTE are widely expressed and evolutionarily conserved. RTE also promoted RNA export from Xenopus oocyte nuclei. RTE-mediated RNA transport was CRM1 independent, and RTE did not show high affinity for binding to mRNA export factor TAP/NXF1. Since CRM1 and TAP/NXF1 are critical export receptors associated with the two recognized mRNA export pathways, these results suggest that RTE functions via a distinct export mechanism. Taken together, our results identify a novel posttranscriptional control element that uses a conserved cellular export mechanism. JF - Journal of virology AU - Nappi, F AU - Schneider, R AU - Zolotukhin, A AU - Smulevitch, S AU - Michalowski, D AU - Bear, J AU - Felber, B K AU - Pavlakis, G N AD - Human Retrovirus Section, Basic Research Laboratory, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 4558 EP - 4569 VL - 75 IS - 10 SN - 0022-538X, 0022-538X KW - Carrier Proteins KW - 0 KW - DNA, Viral KW - Gene Products, rev KW - Karyopherins KW - NXF1 protein, human KW - Nuclear Proteins KW - Nucleocytoplasmic Transport Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Receptors, Cytoplasmic and Nuclear KW - exportin 1 protein KW - rev Gene Products, Human Immunodeficiency Virus KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Active Transport, Cell Nucleus KW - Animals KW - Carrier Proteins -- metabolism KW - RNA-Binding Proteins -- metabolism KW - Humans KW - Jurkat Cells KW - Mice KW - Cloning, Molecular KW - Mutagenesis KW - Xenopus laevis KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - RNA -- metabolism KW - Proviruses -- genetics KW - Genes, Intracisternal A-Particle KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - HIV-1 -- genetics KW - Genes, env -- genetics KW - RNA, Messenger -- metabolism KW - Gene Products, rev -- genetics KW - RNA Processing, Post-Transcriptional KW - Genes, Regulator UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77071912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+of+a+novel+posttranscriptional+regulatory+element+by+using+a+rev-+and+RRE-mutated+human+immunodeficiency+virus+type+1+DNA+proviral+clone+as+a+molecular+trap.&rft.au=Nappi%2C+F%3BSchneider%2C+R%3BZolotukhin%2C+A%3BSmulevitch%2C+S%3BMichalowski%2C+D%3BBear%2C+J%3BFelber%2C+B+K%3BPavlakis%2C+G+N&rft.aulast=Nappi&rft.aufirst=F&rft.date=2001-05-01&rft.volume=75&rft.issue=10&rft.spage=4558&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF250999; GENBANK; AF250998; AF251000 N1 - SuppNotes - Cited By: Exp Cell Res. 1995 Mar;217(1):31-41 [7867718] Genes Dev. 1995 Jul 15;9(14):1766-80 [7542615] Virology. 1995 Nov 10;213(2):439-49 [7491768] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11940-4 [8524879] J Virol. 1996 Jun;70(6):3834-43 [8648719] J Virol. 1996 Sep;70(9):5998-6011 [8709222] Bioinformatics. 1998;14(1):68-73 [9520503] Mol Cell. 1998 Apr;1(5):649-59 [9660949] J Virol. 1998 Sep;72(9):7593-7 [9696859] J Virol. 1998 Nov;72(11):8627-35 [9765402] Genes Dev. 1998 Nov 1;12(21):3303-19 [9808617] EMBO J. 1999 Mar 15;18(6):1642-52 [10075934] J Biol Chem. 2000 Mar 24;275(12):8361-8 [10722667] J Gen Virol. 1996 Nov;77 ( Pt 11):2757-65 [8922469] J Virol. 1997 Jan;71(1):95-101 [8985327] Chem Biol. 1997 Feb;4(2):139-47 [9190288] J Biol Chem. 1997 Apr 25;272(17):11356-60 [9111043] Curr Opin Cell Biol. 1997 Jun;9(3):420-9 [9159083] Virology. 1997 Jun 9;232(2):291-9 [9191842] EMBO J. 1997 Jun 2;16(11):3256-71 [9214641] Curr Biol. 1997 Sep 1;7(9):619-28 [9285715] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10104-9 [9294170] Cell. 1997 Sep 19;90(6):1051-60 [9323133] Curr Biol. 1997 Oct 1;7(10):767-75 [9368759] J Virol. 1997 Dec;71(12):9817-22 [9371653] Nature. 1997 Nov 20;390(6657):308-11 [9384386] EMBO J. 1997 Dec 15;16(24):7500-10 [9405378] Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14394-9 [9405623] J Virol. 1998 Apr;72(4):3407-11 [9525671] J Virol. 1998 Jun;72(6):5085-92 [9573279] RNA. 1998 Apr;4(4):351-64 [9630243] J Virol. 2000 Oct;74(20):9507-14 [11000220] RNA. 2000 Dec;6(12):1762-72 [11142376] Virology. 1973 Apr;52(2):456-67 [4705382] J Gen Virol. 1977 Jul;36(1):59-74 [886304] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Proc Natl Acad Sci U S A. 1983 Apr;80(7):1992-6 [6300886] EMBO J. 1999 Apr 1;18(7):1953-65 [10202158] EMBO J. 1999 May 4;18(9):2593-609 [10228171] Genes Dev. 1999 May 1;13(9):1126-39 [10323864] Arch Biochem Biophys. 1999 May 15;365(2):186-91 [10328811] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9112-7 [10430904] Annu Rev Genet. 1999;33:133-70 [10690406] Proc Natl Acad Sci U S A. 1983 Dec;80(23):7118-22 [6316344] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Cell. 1984 Oct;38(3):731-6 [6567484] Nucleic Acids Res. 1984 Nov 26;12(22):8579-93 [6095203] Mol Cell Biol. 1984 Dec;4(12):2565-72 [6098810] Mol Cell Biol. 1985 Mar;5(3):474-83 [2859519] J Virol. 1986 Aug;59(2):284-91 [3016298] Nucleic Acids Res. 1986 Jul 25;14(14):5901-18 [3016667] Mol Cell Biol. 1985 Dec;5(12):3625-8 [3939322] Virology. 1987 Apr;157(2):317-29 [2435057] Adv Cancer Res. 1988;51:183-276 [3146900] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] Nucleic Acids Res. 1989 Mar 11;17(5):1881-92 [2564662] EMBO J. 1988 Dec 20;7(13):4283-90 [2907477] Cell. 1989 Oct 6;59(1):159-69 [2790958] J Exp Med. 1990 Mar 1;171(3):965-70 [2106569] EMBO J. 1990 Apr;9(4):1087-96 [2108861] J Virol. 1990 Jun;64(6):2519-29 [2335812] Cell. 1990 Oct 5;63(1):109-18 [2208274] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787-91 [2217212] J Virol. 1991 Apr;65(4):2131-4 [2002556] EMBO J. 1992 Jan;11(1):335-43 [1740112] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60 [8108397] J Cell Biol. 1994 Mar;124(5):627-35 [7509815] J Virol. 1994 May;68(5):3193-9 [8151782] EMBO J. 1994 Sep 1;13(17):4105-12 [8076606] J Virol. 1994 Dec;68(12):7944-52 [7966585] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3. AN - 77071576; 11312329 AB - Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3. JF - Journal of virology AU - Schmidt, A C AU - McAuliffe, J M AU - Murphy, B R AU - Collins, P L AD - Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. aschmidt@niaid.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 4594 EP - 4603 VL - 75 IS - 10 SN - 0022-538X, 0022-538X KW - Antibodies, Viral KW - 0 KW - Antigens, Viral KW - DNA, Viral KW - Parainfluenza Vaccines KW - Respiratory Syncytial Virus Vaccines KW - Vaccines, Synthetic KW - Viral Envelope Proteins KW - Viral Fusion Proteins KW - Viral Proteins KW - Index Medicus KW - Virus Replication KW - Animals KW - Respiratory System -- metabolism KW - Open Reading Frames KW - Humans KW - Gene Expression KW - Immunity, Mucosal KW - Vaccination KW - Antibodies, Viral -- biosynthesis KW - Antibodies, Viral -- blood KW - Base Sequence KW - Cattle KW - Tumor Cells, Cultured KW - Recombination, Genetic KW - Molecular Sequence Data KW - Macaca mulatta KW - Mutagenesis, Insertional KW - Cell Line KW - Cricetinae KW - Viral Proteins -- immunology KW - Viral Proteins -- genetics KW - Respiratory Syncytial Virus Vaccines -- immunology KW - Genetic Vectors -- immunology KW - Respirovirus Infections -- prevention & control KW - Parainfluenza Vaccines -- genetics KW - Viral Fusion Proteins -- genetics KW - Respirovirus -- genetics KW - Respiratory Syncytial Virus, Human -- immunology KW - Viral Fusion Proteins -- immunology KW - Viral Envelope Proteins -- immunology KW - Respirovirus -- physiology KW - Parainfluenza Vaccines -- immunology KW - Genetic Vectors -- physiology KW - Antigens, Viral -- immunology KW - Parainfluenza Virus 3, Human -- genetics KW - Vaccines, Synthetic -- immunology KW - Respirovirus -- immunology KW - Vaccines, Synthetic -- genetics KW - Respiratory Syncytial Virus Infections -- prevention & control KW - Antigens, Viral -- genetics KW - Genetic Vectors -- genetics KW - Parainfluenza Virus 3, Human -- immunology KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77071576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Recombinant+bovine%2Fhuman+parainfluenza+virus+type+3+%28B%2FHPIV3%29+expressing+the+respiratory+syncytial+virus+%28RSV%29+G+and+F+proteins+can+be+used+to+achieve+simultaneous+mucosal+immunization+against+RSV+and+HPIV3.&rft.au=Schmidt%2C+A+C%3BMcAuliffe%2C+J+M%3BMurphy%2C+B+R%3BCollins%2C+P+L&rft.aulast=Schmidt&rft.aufirst=A&rft.date=2001-05-01&rft.volume=75&rft.issue=10&rft.spage=4594&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1987 Aug;84(15):5134-8 [2440043] Vaccine. 1999 Jun 4;17(20-21):2715-25 [10418923] J Virol. 1988 Oct;62(10):3907-10 [3047432] J Clin Microbiol. 1988 Aug;26(8):1595-7 [2459154] Virus Res. 1988 Aug;11(1):1-15 [2845680] J Virol. 1989 Jul;63(7):2941-50 [2470922] Vaccine. 1990 Oct;8(5):497-502 [2251875] J Clin Microbiol. 1991 Jun;29(6):1175-82 [1650789] J Virol. 1992 Feb;66(2):1277-81 [1731105] J Clin Microbiol. 1992 Mar;30(3):655-62 [1551982] Vaccine. 1992;10(7):475-84 [1609551] Virus Res. 1992 Mar;22(3):173-84 [1320790] Virus Res. 1992 Sep 1;25(1-2):37-50 [1413993] Adv Exp Med Biol. 1992;327:59-69 [1295353] J Virol. 1993 Aug;67(8):4822-30 [8392616] J Exp Med. 1994 Jan 1;179(1):81-9 [8270885] Vaccine. 1993 Nov;11(14):1395-404 [8310760] J Virol. 1995 Feb;69(2):1261-4 [7815502] J Infect Dis. 1995 May;171(5):1107-14 [7751684] Vaccine. 1995 Mar;13(4):415-21 [7793140] J Infect Dis. 1995 Dec;172(6):1445-50 [7594701] J Infect Dis. 1996 Apr;173(4):829-39 [8603960] J Infect Dis. 1996 Mar;173(3):592-7 [8627022] Virus Res. 1995 Dec;39(2-3):105-18 [8837878] Pediatr Infect Dis J. 1996 Aug;15(8):650-4 [8858666] Vaccine. 1997 Apr;15(5):533-40 [9160521] JAMA. 1999 Oct 20;282(15):1440-6 [10535434] Adv Virus Res. 1999;54:423-51 [10547682] Vaccine. 2000 Jan 31;18(14):1359-66 [10618533] J Virol. 2000 Apr;74(7):3188-95 [10708435] J Virol. 2000 Jul;74(14):6448-58 [10864657] Virus Genes. 2000;20(2):173-82 [10872880] Virology. 2000 Jun 20;272(1):225-34 [10873765] J Virol. 2000 Aug;74(15):6821-31 [10888621] J Virol. 2000 Oct;74(19):8922-9 [10982335] J Infect Dis. 2000 Nov;182(5):1331-42 [11010838] J Infect Dis. 2001 Jan 1;183(1):16-22 [11076709] J Bacteriol. 1966 Mar;91(3):1263-9 [5929754] Am J Epidemiol. 1966 Mar;83(2):299-313 [5933417] Am J Epidemiol. 1969 Apr;89(4):422-34 [4305198] Pediatrics. 1971 Nov;48(5):745-55 [4330595] Infect Immun. 1982 Jul;37(1):397-400 [7107009] J Med Virol. 1986 Feb;18(2):131-7 [3005486] Proc Natl Acad Sci U S A. 1986 Mar;83(6):1906-10 [3513191] J Clin Microbiol. 1986 Aug;24(2):197-202 [3755730] J Virol. 1986 Oct;60(1):90-6 [2427750] J Clin Microbiol. 1986 Nov;24(5):894-8 [3771779] Virology. 1995 Jun 20;210(1):202-5 [7793072] J Exp Med. 1997 Aug 4;186(3):421-32 [9236194] J Virol. 1997 Sep;71(9):6935-9 [9261421] Virology. 1997 Sep 1;235(2):323-32 [9281512] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6 [9391135] J Infect Dis. 1997 Dec;176(6):1428-36 [9395351] Eur J Immunol. 1997 Dec;27(12):3341-9 [9464822] J Virol. 1998 Apr;72(4):3117-28 [9525637] J Exp Med. 1998 Jun 1;187(11):1921-6 [9607931] Clin Microbiol Rev. 1998 Jul;11(3):430-9 [9665976] Pediatr Infect Dis J. 1998 Oct;17(10):919-20 [9802636] J Virol. 1999 Feb;73(2):871-7 [9882287] J Infect Dis. 1988 Apr;157(4):655-62 [2831282] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase. AN - 77064012; 11312355 AB - Two distinct mechanisms can be envisioned for resistance of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to nucleoside analogs: one in which the mutations interfere with the ability of HIV-1 RT to incorporate the analog, and the other in which the mutations enhance the excision of the analog after it has been incorporated. It has been clear for some time that there are mutations that selectively interfere with the incorporation of nucleoside analogs; however, it has only recently been proposed that zidovudine (AZT) resistance can involve the excision of the nucleoside analog after it has been incorporated into viral DNA. Although this proposal resolves some important issues, it leaves some questions unanswered. In particular, how do the AZT resistance mutations enhance excision, and what mechanism(s) causes the excision reaction to be relatively specific for AZT? We have used both structural and biochemical data to develop a model. In this model, several of the mutations associated with AZT resistance act primarily to enhance the binding of ATP, which is the most likely pyrophosphate donor in the in vivo excision reaction. The AZT resistance mutations serve to increase the affinity of RT for ATP so that, at physiological ATP concentrations, excision is reasonably efficient. So far as we can determine, the specificity of the excision reaction for an AZT-terminated primer is not due to the mutations that confer resistance, but depends instead on the structure of the region around the HIV-1 RT polymerase active site and on its interactions with the azido group of AZT. Steric constraints involving the azido group cause the end of an AZT 5'-monophosphate-terminated primer to preferentially reside at the nucleotide binding site, which favors excision. JF - Journal of virology AU - Boyer, P L AU - Sarafianos, S G AU - Arnold, E AU - Hughes, S H AD - ABL Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 4832 EP - 4842 VL - 75 IS - 10 SN - 0022-538X, 0022-538X KW - Anti-HIV Agents KW - 0 KW - Dideoxynucleotides KW - Reverse Transcriptase Inhibitors KW - Thymine Nucleotides KW - 3'-azido-3'-deoxythymidine 5'phosphate KW - 29706-85-2 KW - Zidovudine KW - 4B9XT59T7S KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Adenosine Triphosphate -- metabolism KW - Drug Resistance KW - Protein Conformation KW - Mutagenesis KW - Adenosine Triphosphate -- chemistry KW - Zidovudine -- analogs & derivatives KW - Thymine Nucleotides -- metabolism KW - Anti-HIV Agents -- metabolism KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Zidovudine -- pharmacology KW - HIV Reverse Transcriptase -- chemistry KW - HIV-1 -- enzymology KW - HIV Reverse Transcriptase -- genetics KW - Reverse Transcriptase Inhibitors -- metabolism KW - Zidovudine -- metabolism KW - Anti-HIV Agents -- pharmacology KW - Thymine Nucleotides -- pharmacology KW - HIV Reverse Transcriptase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77064012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Selective+excision+of+AZTMP+by+drug-resistant+human+immunodeficiency+virus+reverse+transcriptase.&rft.au=Boyer%2C+P+L%3BSarafianos%2C+S+G%3BArnold%2C+E%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=2001-05-01&rft.volume=75&rft.issue=10&rft.spage=4832&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1997 May 13;36(19):5749-57 [9153415] J Biol Chem. 1995 Oct 6;270(40):23605-11 [7559526] Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13471-6 [9811824] Science. 1998 Nov 27;282(5394):1669-75 [9831551] J Mol Biol. 1998 Dec 11;284(4):1095-111 [9837729] Biochemistry. 1998 Nov 10;37(45):15908-17 [9843396] J Mol Biol. 1999 Mar 5;286(4):995-1008 [10047477] Mol Cell. 1999 Jul;4(1):35-43 [10445025] Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10027-32 [10468556] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3056-61 [10737786] J Mol Biol. 2000 Jul 7;300(2):403-18 [10873473] J Virol. 2000 Oct;74(20):9532-9 [11000223] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] Gene. 1987;56(1):125-35 [3315856] Science. 1989 Dec 1;246(4934):1155-8 [2479983] Eur J Biochem. 1990 Jan 26;187(2):307-14 [1688798] EMBO J. 1991 Dec;10(12):3905-11 [1718745] J Virol. 1992 Feb;66(2):1031-9 [1370546] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):549-53 [7507249] Antimicrob Agents Chemother. 1994 Sep;38(9):1909-14 [7529011] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2398-402 [7534421] J Biol Chem. 1998 Oct 23;273(43):28384-91 [9774465] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function studies of human deoxyhypusine synthase: identification of amino acid residues critical for the binding of spermidine and NAD. AN - 77063468; 11311149 AB - Deoxyhypusine synthase catalyses the first step in the biosynthesis of hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. The crystal structure of human deoxyhypusine synthase in complex with NAD revealed four NAD-binding sites per enzyme tetramer, and led to a prediction of the spermidine-binding pocket. We have replaced each of the seven amino acid residues at the predicted spermidine-binding site, and eleven residues that contact NAD, on an individual basis with alanine. Of the amino acid residues at the spermidine site, substitution of Asp-243, Trp-327, His-288, Asp-316 or Glu-323 with alanine caused an almost complete loss of spermidine binding and enzyme activity; only the mutation Tyr-305-->Ala showed partial binding and activity. His-288-->Ala was also deficient in terms of binding NAD. NAD binding was significantly reduced in all of the NAD-site mutant enzymes, except for Glu-137-->Ala, which showed a normal binding of NAD, but was totally lacking in spermidine binding. Of the NAD-site mutant enzymes, Asp-342-->Ala, Asp-313-->Ala and Asp-238-->Ala displayed the lowest binding of NAD. These enzymes and His-288Ala also showed a reduced binding of spermidine, presumably because spermidine binding is dependent on NAD. These findings permit the positive identification of amino acid residues critical for binding of spermidine and NAD, and provide a new insight into the complex molecular interactions involved in the deoxyhypusine synthase reaction. JF - The Biochemical journal AU - Lee, C H AU - Um, P Y AU - Park, M H AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4340, USA. Y1 - 2001/05/01/ PY - 2001 DA - 2001 May 01 SP - 841 EP - 849 VL - 355 SN - 0264-6021, 0264-6021 KW - Amino Acids KW - 0 KW - Eukaryotic Initiation Factor-5 KW - Peptide Initiation Factors KW - NAD KW - 0U46U6E8UK KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - deoxyhypusine synthase KW - EC 1.5.1.- KW - Spermidine KW - U87FK77H25 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Peptide Initiation Factors -- metabolism KW - Kinetics KW - Humans KW - Amino Acids -- metabolism KW - Structure-Activity Relationship KW - Binding Sites KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - NAD -- chemistry KW - Spermidine -- metabolism KW - NAD -- metabolism KW - Spermidine -- chemistry KW - Oxidoreductases Acting on CH-NH Group Donors -- genetics KW - Oxidoreductases Acting on CH-NH Group Donors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77063468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Structure-function+studies+of+human+deoxyhypusine+synthase%3A+identification+of+amino+acid+residues+critical+for+the+binding+of+spermidine+and+NAD.&rft.au=Lee%2C+C+H%3BUm%2C+P+Y%3BPark%2C+M+H&rft.aulast=Lee&rft.aufirst=C&rft.date=2001-05-01&rft.volume=355&rft.issue=&rft.spage=841&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2000 Mar 31;275(13):9170-7 [10734052] Biochem J. 1999 May 15;340 ( Pt 1):273-81 [10229683] Anal Biochem. 1983 Jul 1;132(1):74-81 [6312839] Biomed Biochim Acta. 1983;42(5):537-46 [6316944] J Biol Chem. 1986 Mar 5;261(7):3085-9 [3949761] J Biol Chem. 1987 Nov 5;262(31):15033-6 [3117792] FEBS Lett. 1988 Mar 14;229(2):325-8 [3126083] J Biol Chem. 1988 Oct 25;263(30):15264-9 [3139668] J Biol Chem. 1990 Mar 25;265(9):4793-9 [2108161] Mol Cell Biol. 1991 Jun;11(6):3105-14 [1903841] Biochem J. 1992 Nov 1;287 ( Pt 3):717-24 [1445235] J Biol Chem. 1993 Jun 25;268(18):13151-9 [8514754] Mol Gen Genet. 1993 Nov;241(3-4):305-11 [8246884] Trends Biochem Sci. 1993 Dec;18(12):475-9 [8108861] Biochim Biophys Acta. 1994 Mar 31;1221(2):115-24 [8148388] J Biol Chem. 1994 Oct 14;269(41):25916-21 [7929297] J Biol Chem. 1994 Nov 11;269(45):27827-32 [7961711] Biochem J. 1994 Oct 15;303 ( Pt 2):363-8 [7980394] J Biol Chem. 1995 Apr 14;270(15):8660-6 [7721768] Eur J Biochem. 1995 Dec 1;234(2):603-15 [8536710] Science. 1996 Jan 12;271(5246):163-8 [8539615] J Biol Chem. 1996 Apr 19;271(16):9519-25 [8621624] FEBS Lett. 1996 Apr 15;384(2):151-4 [8612813] J Biol Chem. 1996 May 24;271(21):12205-8 [8647815] J Biol Chem. 1997 Jun 20;272(25):15865-71 [9188485] Biol Signals. 1997 May-Jun;6(3):105-9 [9285092] Biol Signals. 1997 May-Jun;6(3):115-23 [9285094] J Biol Chem. 1997 Dec 19;272(51):32679-85 [9405486] J Biol Chem. 1998 Jan 16;273(3):1677-83 [9430712] Structure. 1998 Jan 15;6(1):23-32 [9493264] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10419-24 [9724718] Structure. 1998 Sep 15;6(9):1207-14 [9753699] Biochem J. 2000 Dec 15;352 Pt 3:851-7 [11104695] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. AN - 77055020; 11303069 AB - Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress. JF - The Journal of pharmacology and experimental therapeutics AU - Spong, C Y AU - Abebe, D T AU - Gozes, I AU - Brenneman, D E AU - Hill, J M AD - Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. spongc@exchange.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 774 EP - 779 VL - 297 IS - 2 SN - 0022-3565, 0022-3565 KW - Oligopeptides KW - 0 KW - activity-dependent neurotrophic factor KW - Ethanol KW - 3K9958V90M KW - Glutathione KW - GAN16C9B8O KW - davunetide KW - GF00K3IIWE KW - Index Medicus KW - Litter Size -- drug effects KW - Ethanol -- blood KW - Animals KW - Glutathione -- metabolism KW - Oxidative Stress -- drug effects KW - Mice, Inbred C57BL KW - Mice KW - Birth Weight -- drug effects KW - Female KW - Pregnancy KW - Biological Availability KW - Oligopeptides -- pharmacokinetics KW - Fetal Death -- prevention & control KW - Oligopeptides -- pharmacology KW - Fetal Growth Retardation -- prevention & control KW - Fetal Death -- pathology KW - Fetal Growth Retardation -- pathology KW - Fetal Alcohol Spectrum Disorders -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77055020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Prevention+of+fetal+demise+and+growth+restriction+in+a+mouse+model+of+fetal+alcohol+syndrome.&rft.au=Spong%2C+C+Y%3BAbebe%2C+D+T%3BGozes%2C+I%3BBrenneman%2C+D+E%3BHill%2C+J+M&rft.aulast=Spong&rft.aufirst=C&rft.date=2001-05-01&rft.volume=297&rft.issue=2&rft.spage=774&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats. AN - 77054612; 11303040 AB - Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administered to primates, ibogaine is rapidly o-demethylated to form the metabolite 12-hydroxyibogamine (noribogaine). Peak blood levels of noribogaine exceed those of ibogaine, and noribogaine persists in the bloodstream for at least 1 day. Very few studies have systematically evaluated the neurobiological effects of noribogaine in vivo. In the present series of experiments, we compared the effects of i.v. administration of ibogaine and noribogaine (1 and 10 mg/kg) on motor behaviors, stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. Ibogaine caused dose-related increases in tremors, whereas noribogaine did not. Both ibogaine and noribogaine produced significant elevations in plasma corticosterone and prolactin, but ibogaine was a more potent stimulator of corticosterone secretion. Neither drug altered extracellular DA levels in the nucleus accumbens. However, both drugs increased extracellular 5-HT levels, and noribogaine was more potent in this respect. Results from in vitro experiments indicated that ibogaine and noribogaine interact with 5-HT transporters to inhibit 5-HT uptake. The present findings demonstrate that noribogaine is biologically active and undoubtedly contributes to the in vivo pharmacological profile of ibogaine in rats. Noribogaine is approximately 10 times more potent than ibogaine as an indirect 5-HT agonist. More importantly, noribogaine appears less apt to produce the adverse effects associated with ibogaine, indicating the metabolite may be a safer alternative for medication development. JF - The Journal of pharmacology and experimental therapeutics AU - Baumann, M H AU - Rothman, R B AU - Pablo, J P AU - Mash, D C AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. mbaumann@intra.nida.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 531 EP - 539 VL - 297 IS - 2 SN - 0022-3565, 0022-3565 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Neurotoxins KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, rat KW - noribogaine KW - Ibogaine KW - 3S814I130U KW - Index Medicus KW - Rats KW - Microdialysis KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Carrier Proteins -- metabolism KW - Brain Chemistry -- drug effects KW - Male KW - Membrane Glycoproteins -- metabolism KW - Ibogaine -- toxicity KW - Neurotoxins -- pharmacokinetics KW - Ibogaine -- analogs & derivatives KW - Neurotoxins -- toxicity KW - Ibogaine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77054612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=In+vivo+neurobiological+effects+of+ibogaine+and+its+O-desmethyl+metabolite%2C+12-hydroxyibogamine+%28noribogaine%29%2C+in+rats.&rft.au=Baumann%2C+M+H%3BRothman%2C+R+B%3BPablo%2C+J+P%3BMash%2C+D+C&rft.aulast=Baumann&rft.aufirst=M&rft.date=2001-05-01&rft.volume=297&rft.issue=2&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L1 interaction domains of papillomavirus l2 necessary for viral genome encapsidation. AN - 77037114; 11287582 AB - BPHE-1 cells, which harbor 50 to 200 viral episomes, encapsidate viral genome and generate infectious bovine papillomavirus type 1 (BPV1) upon coexpression of capsid proteins L1 and L2 of BPV1, but not coexpression of BPV1 L1 and human papillomavirus type 16 (HPV16) L2. BPV1 L2 bound in vitro via its C-terminal 85 residues to purified L1 capsomers, but not with intact L1 virus-like particles in vitro. However, when the efficiency of BPV1 L1 coimmunoprecipitation with a series of BPV1 L2 deletion mutants was examined in vivo, the results suggested that residues 129 to 246 and 384 to 460 contain independent L1 interaction domains. An L2 mutant lacking the C-terminal L1 interaction domain was impaired for encapsidation of the viral genome. Coexpression of BPV1 L1 and a chimeric L2 protein composed of HPV16 L2 residues 1 to 98 fused to BPV1 L2 residues 99 to 469 generated infectious virions. However, inefficient encapsidation was seen when L1 was coexpressed with either BPV1 L2 with residues 91 to 246 deleted or with BPV1 L2 with residues 1 to 225 replaced with HPV16 L2. Impaired genome encapsidation did not correlate closely with impairment of the L2 proteins either to localize to promyelocytic leukemia oncogenic domains (PODs) or to induce localization of L1 or E2 to PODs. We conclude that the L1-binding domain located near the C terminus of L2 may bind L1 prior to completion of capsid assembly, and that both L1-binding domains of L2 are required for efficient encapsidation of the viral genome. JF - Journal of virology AU - Okun, M M AU - Day, P M AU - Greenstone, H L AU - Booy, F P AU - Lowy, D R AU - Schiller, J T AU - Roden, R B AD - Laboratory of Cellular Oncology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 4332 EP - 4342 VL - 75 IS - 9 SN - 0022-538X, 0022-538X KW - Capsid Proteins KW - 0 KW - L1 protein, Bovine papillomavirus KW - L2 protein, Bovine papillomavirus KW - L2 protein, Human papillomavirus type 16 KW - Oncogene Proteins, Viral KW - Index Medicus KW - Animals KW - Cattle KW - Humans KW - Papillomaviridae -- metabolism KW - Oncogene Proteins, Viral -- genetics KW - Papillomaviridae -- genetics KW - Precipitin Tests KW - Oncogene Proteins, Viral -- metabolism KW - Cell Line KW - Mutagenesis KW - Cricetinae KW - Binding Sites KW - Bovine papillomavirus 1 -- metabolism KW - Virus Assembly -- physiology KW - Capsid -- genetics KW - Capsid -- metabolism KW - Genome, Viral KW - Bovine papillomavirus 1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77037114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=L1+interaction+domains+of+papillomavirus+l2+necessary+for+viral+genome+encapsidation.&rft.au=Okun%2C+M+M%3BDay%2C+P+M%3BGreenstone%2C+H+L%3BBooy%2C+F+P%3BLowy%2C+D+R%3BSchiller%2C+J+T%3BRoden%2C+R+B&rft.aulast=Okun&rft.aufirst=M&rft.date=2001-05-01&rft.volume=75&rft.issue=9&rft.spage=4332&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 2000 Apr;74(8):3761-70 [10729151] Virology. 1999 Jun 20;259(1):211-8 [10364505] Virology. 2000 Oct 25;276(2):304-14 [11040122] Virology. 1980 Jun;103(2):369-75 [6247821] Proc Natl Acad Sci U S A. 1981 May;78(5):2727-31 [6265905] EMBO J. 1987 Apr;6(4):1027-35 [3036488] J Virol. 1987 Sep;61(9):2793-9 [3039170] J Virol. 1987 Sep;61(9):2924-8 [3039179] J Gen Virol. 1989 May;70 ( Pt 5):1133-40 [2471804] Biotechnology (N Y). 1991 Dec;9(12):1356-61 [1370252] Biophys J. 1991 Dec;60(6):1445-56 [1663794] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12180-4 [1334560] J Gen Virol. 1993 Apr;74 ( Pt 4):763-8 [8385700] J Virol. 1993 Dec;67(12):6929-36 [8230414] J Virol. 1994 Nov;68(11):7570-4 [7523700] J Gen Virol. 1995 May;76 ( Pt 5):1141-53 [7537325] J Gen Virol. 1995 Sep;76 ( Pt 9):2407-12 [7561785] J Gen Virol. 1995 Nov;76 ( Pt 11):2661-7 [7595373] J Virol. 1995 Dec;69(12):7734-42 [7494283] J Virol. 1996 Sep;70(9):5875-83 [8709207] J Cell Biochem. 1996 Dec 1;63(3):280-91 [8913879] Virology. 1997 Jan 20;227(2):474-83 [9018146] J Virol. 1997 Apr;71(4):2934-9 [9060652] Nat Struct Biol. 1997 May;4(5):413-20 [9145113] J Virol. 1997 Aug;71(8):6247-52 [9223527] Genes Cells. 1997 Sep;2(9):537-45 [9413995] J Virol. 1998 Jan;72(1):32-41 [9420197] J Virol. 1998 Jan;72(1):142-50 [9420209] Nucleic Acids Res. 1998 Mar 1;26(5):1317-23 [9469843] J Virol. 1998 Mar;72(3):1994-2001 [9499053] J Virol. 1998 Mar;72(3):2160-7 [9499072] Virology. 1998 Apr 10;243(2):482-91 [9568045] J Mol Biol. 1998 Oct 30;283(3):529-36 [9784363] J Virol. 1999 Feb;73(2):1001-9 [9882301] J Biol Chem. 1999 Apr 23;274(17):11832-41 [10207001] J Virol. 1999 Jul;73(7):6188-90 [10364381] Virology. 2000 Jul 5;272(2):382-93 [10873782] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes. AN - 77033469; 11287578 AB - Infection with high-risk human papillomaviruses (HPV) is a major risk factor for development of cervical cancer. Expression of the HPV E6 and E7 oncoproteins increases in differentiating keratinocytes, resulting in inactivation of the p53 and retinoblastoma proteins, two important transcriptional regulators. We used cDNA microarrays to examine global alterations in gene expression in differentiating cervical keratinocytes after infection with retroviruses encoding HPV type 16 (HPV-16) E6 and E7. Expression of 80 cellular genes (approximately 4% of the genes on the array) was altered reproducibly by E6 and/or E7. Cluster analysis classified these genes into three functional groups: (i) interferon (IFN)-responsive genes, (ii) genes stimulated by NF-kappaB, and (iii) genes regulated in cell cycle progression and DNA synthesis. HPV-16 E6 or a dominant negative p53 protein downregulated multiple IFN-responsive genes. E6 decreased expression of IFN-alpha and -beta, downregulated nuclear STAT-1 protein, and decreased binding of STAT-1 to the IFN-stimulated response element. E7 alone was less effective; however, coexpression of E6 and E7 downregulated IFN-responsive genes more efficiently than E6. The HPV-16 E6 protein also stimulated expression of multiple genes known to be inducible by NF-kappaB and AP-1. E6 enhanced expression of functional components of the NF-kappaB signal pathway, including p50, NIK, and TRAF-interacting protein, and increased binding to NF-kappaB and AP-1 DNA consensus binding sites. Secretion of interleukin-8, RANTES, macrophage inflammatory protein 1alpha, and 10-kappaDa IFN-gamma-inducible protein were increased in differentiating keratinocytes by E6. Thus, high-level expression of the HPV-16 E6 protein in differentiating keratinocytes directly alters expression of genes that influence host resistance to infection and immune function. JF - Journal of virology AU - Nees, M AU - Geoghegan, J M AU - Hyman, T AU - Frank, S AU - Miller, L AU - Woodworth, C D AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 4283 EP - 4296 VL - 75 IS - 9 SN - 0022-538X, 0022-538X KW - Cytokines KW - 0 KW - DNA-Binding Proteins KW - E6 protein, Human papillomavirus type 16 KW - Interferon Type I KW - Interferon-alpha KW - NF-kappa B KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - Trans-Activators KW - Transcription Factor AP-1 KW - Transcription Factors KW - oncogene protein E7, Human papillomavirus type 16 KW - Interferon-beta KW - 77238-31-4 KW - Interferon-gamma KW - 82115-62-6 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Interferon-alpha -- pharmacology KW - Interferon-beta -- pharmacology KW - Oligonucleotide Array Sequence Analysis KW - Transcription Factor AP-1 -- metabolism KW - Humans KW - Cytokines -- secretion KW - Gene Expression KW - DNA-Binding Proteins -- genetics KW - Interferon-gamma -- pharmacology KW - Oncogenes KW - Trans-Activators -- genetics KW - Interferon Type I -- pharmacology KW - Keratinocytes -- cytology KW - Interferon-alpha -- genetics KW - Keratinocytes -- metabolism KW - Response Elements KW - Cell Cycle KW - Interferon-beta -- genetics KW - DNA-Binding Proteins -- metabolism KW - Cell Division KW - DNA -- metabolism KW - Cells, Cultured KW - Cervix Uteri -- cytology KW - Female KW - Down-Regulation KW - Transcription Factors -- metabolism KW - Papillomaviridae -- metabolism KW - Oncogene Proteins, Viral -- genetics KW - Papillomaviridae -- genetics KW - Up-Regulation KW - Transcription Factors -- genetics KW - Oncogene Proteins, Viral -- metabolism KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77033469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Papillomavirus+type+16+oncogenes+downregulate+expression+of+interferon-responsive+genes+and+upregulate+proliferation-associated+and+NF-kappaB-responsive+genes+in+cervical+keratinocytes.&rft.au=Nees%2C+M%3BGeoghegan%2C+J+M%3BHyman%2C+T%3BFrank%2C+S%3BMiller%2C+L%3BWoodworth%2C+C+D&rft.aulast=Nees&rft.aufirst=M&rft.date=2001-05-01&rft.volume=75&rft.issue=9&rft.spage=4283&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1999 Sep 15;18(18):5061-72 [10487758] Genes Cells. 1996 Nov;1(11):995-1005 [9077462] Science. 1999 Oct 15;286(5439):531-7 [10521349] Oncol Rep. 1999 Nov-Dec;6(6):1405-10 [10523720] Oncogene. 1999 Oct 14;18(42):5727-37 [10523853] J Biol Chem. 2000 Mar 17;275(11):7558-65 [10713062] J Virol. 2000 May;74(9):4174-82 [10756030] J Invest Dermatol. 1999 Dec;113(6):920-7 [10594731] Oncogene. 1999 Nov 22;18(49):6853-66 [10602461] Oncogene. 1999 Dec 9;18(52):7423-31 [10602501] Nature. 2000 Feb 3;403(6769):503-11 [10676951] J Biol Chem. 2000 Mar 10;275(10):6764-9 [10702232] J Biol Chem. 1997 Jul 4;272(27):16917-23 [9202001] Cancer Res. 1997 Aug 15;57(16):3569-76 [9270030] Semin Cancer Biol. 1996 Dec;7(6):327-37 [9284525] Science. 1997 Sep 12;277(5332):1630-5 [9287210] Genomics. 1997 Oct 1;45(1):17-23 [9339356] Oncogene. 1998 May 14;16(19):2447-58 [9627111] Oncogene. 1998 May 28;16(21):2711-21 [9652737] Genes Dev. 1998 Jul 1;12(13):2061-72 [9649509] Biochim Biophys Acta. 1998 Aug 19;1378(1):F1-19 [9739758] Oncogene. 1998 Sep 10;17(10):1195-205 [9771962] Am J Pathol. 1998 Dec;153(6):1849-60 [9846975] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Acta Derm Venereol. 1999 Jan;79(1):9-11 [10086850] Semin Cancer Biol. 1998;8(5):345-57 [10101800] Mol Cell Biol. 1999 May;19(5):3485-95 [10207072] Virology. 1999 Jul 5;259(2):305-13 [10388655] J Biol Chem. 1999 Aug 13;274(33):23358-67 [10438513] J Virol. 1999 Sep;73(9):7297-307 [10438818] Carcinogenesis. 2000 May;21(5):1031-7 [10783329] J Biol Chem. 2000 May 5;275(18):13297-306 [10788436] JAMA. 2000 May 3;283(17):2298-9 [10807394] Int J Mol Med. 2000 Jun;5(6):661-6 [10812019] Biochem Biophys Res Commun. 2000 Jun 7;272(2):375-9 [10833421] Cancer Res. 2000 Aug 1;60(15):4289-98 [10945644] Nature. 2000 Aug 17;406(6797):747-52 [10963602] Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10002-7 [10944189] J Biol Chem. 2000 Sep 8;275(36):27858-64 [10878013] Virology. 2000 Nov 25;277(2):411-9 [11080488] Cancer Res. 1988 Aug 15;48(16):4620-8 [2456144] J Virol. 1989 Oct;63(10):4417-21 [2476573] Cancer Res. 1990 Jun 15;50(12):3709-15 [1692766] Cell. 1990 Dec 21;63(6):1129-36 [2175676] J Virol. 1991 Jan;65(1):473-8 [1845902] Cancer Res. 1991 Nov 1;51(21):5967-75 [1657375] Virology. 1992 Jul;189(1):132-40 [1318602] Int J Cancer. 1992 Jul 9;51(5):831-4 [1319412] J Virol. 1992 Dec;66(12):6893-902 [1331501] Oncogene. 1994 Feb;9(2):387-94 [8290252] EMBO J. 1994 Mar 15;13(6):1368-74 [8137820] Annu Rev Microbiol. 1994;48:427-47 [7826013] Exp Dermatol. 1995 Jun;4(3):138-45 [7551561] Gene Expr. 1995;5(1):1-18 [7488857] Cold Spring Harb Symp Quant Biol. 1994;59:623-8 [7587122] J Immunol. 1996 Feb 1;156(3):1132-37 [8557989] Oncogene. 1996 Apr 18;12(8):1773-9 [8622898] EMBO J. 1996 Apr 15;15(8):1950-60 [8617242] Nat Genet. 1996 Dec;14(4):457-60 [8944026] J Biol Chem. 1999 Oct 22;274(43):30858-63 [10521478] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversible sideroblastic anemia associated with the tetracycline analogue COL-3. AN - 77014397; 11279658 AB - Eight of 35 patients with cancer receiving COL-3, a tetracycline derivative with antiangiogenic properties, developed anemia while on treatment. All of these patients were enrolled on an approved Phase I clinical trial at the National Cancer Institute. Three of these patients had bone marrow examinations that revealed ringed sideroblasts. This paper describes these cases. Am. J. Hematol. 67:51-53, 2001. Published 2001 Wiley-Liss, Inc. JF - American journal of hematology AU - Rudek, M A AU - Horne, M AU - Figg, W D AU - Dahut, W AU - Dyer, V AU - Pluda, J M AU - Reed, E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 51 EP - 53 VL - 67 IS - 1 SN - 0361-8609, 0361-8609 KW - Antibiotics, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Tetracyclines KW - tetracycline CMT-3 KW - Tetracycline KW - F8VB5M810T KW - Index Medicus KW - Bone Marrow -- pathology KW - Antibiotics, Antineoplastic -- administration & dosage KW - Thyroid Neoplasms -- complications KW - Antineoplastic Agents -- administration & dosage KW - Humans KW - Adenocarcinoma, Follicular -- drug therapy KW - Antineoplastic Agents -- adverse effects KW - Adenocarcinoma, Follicular -- complications KW - Adult KW - Thyroid Neoplasms -- drug therapy KW - Middle Aged KW - Antibiotics, Antineoplastic -- adverse effects KW - Female KW - Male KW - Anemia, Sideroblastic -- chemically induced KW - Tetracycline -- administration & dosage KW - Tetracycline -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77014397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hematology&rft.atitle=Reversible+sideroblastic+anemia+associated+with+the+tetracycline+analogue+COL-3.&rft.au=Rudek%2C+M+A%3BHorne%2C+M%3BFigg%2C+W+D%3BDahut%2C+W%3BDyer%2C+V%3BPluda%2C+J+M%3BReed%2C+E&rft.aulast=Rudek&rft.aufirst=M&rft.date=2001-05-01&rft.volume=67&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ongoing trials of immune-based therapies for HIV infection in adults. AN - 72310642; 11727515 AB - Highly active antiretroviral therapy (HAART) can significantly alter the clinical course of patients infected with HIV. Unfortunately, effective lifelong HAART may not be a practical or achievable goal because of toxicities, cost, development of viral resistance and patient compliance issues. Immune-based therapies (IBTs) that target the host immune system may serve as rational additions to our current antiretroviral strategies. Investigations into IL-2 have culminated in two large Phase III clinical trials. Multiple therapeutic vaccine candidates are in various phases of investigation. In addition, gene therapy has been proposed as a potential treatment for HIV and Phase I trials are ongoing. Although IBTs are being investigated on many fronts, they remain difficult to study due to a lack of validated surrogate end points. JF - Expert opinion on biological therapy AU - Ross, R W AU - Wright, M E AU - Tavel, J A AD - Clinical Center & National Institute of Allergy and Infectious Diseases, National Institutes of Health Critical Care Medicine Dept., Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 413 EP - 424 VL - 1 IS - 3 SN - 1471-2598, 1471-2598 KW - AIDS Vaccines KW - 0 KW - Cytokines KW - DNA, Viral KW - Vaccines, DNA KW - Index Medicus KW - HIV-1 -- genetics KW - AIDS Vaccines -- therapeutic use KW - Vaccines, DNA -- therapeutic use KW - Humans KW - DNA, Viral -- immunology KW - Cytokines -- immunology KW - Immunotherapy KW - HIV Infections -- therapy KW - HIV Infections -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72310642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+biological+therapy&rft.atitle=Ongoing+trials+of+immune-based+therapies+for+HIV+infection+in+adults.&rft.au=Ross%2C+R+W%3BWright%2C+M+E%3BTavel%2C+J+A&rft.aulast=Ross&rft.aufirst=R&rft.date=2001-05-01&rft.volume=1&rft.issue=3&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+biological+therapy&rft.issn=14712598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-20 N1 - Date created - 2001-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 51Cr release assay of antibody-dependent cell-mediated cytotoxicity (ADCC). AN - 71445420; 18432838 AB - Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immunologic cytotoxic effector mechanism that is dependent on the cooperative interaction of humoral and cellular effector elements. This unit describes an assay of ADCC activity that can be used as a test for immunocompetence in effector cells or to test the activity of a monoclonal antibody to mediate ADCC. In this form of cytotoxicity, effector cells with receptors for the Fc portion of immunoglobulin produce target cell lysis by attachment to the Fc portion of antibodies that are bound to target cells via their antigen-combining sites. Therefore, an ADCC assay involves three essential components: labeled target cells, antibodies with specificity for target-cell surface antigens, and effector-cell populations. The basic protocol describes a method of measuring ADCC effector activity in lymphoid cells (peripheral blood mononuclear cells, or PBMC) that employs (51)Cr-labeled target cells. The three components are mixed in microtiter-plate wells and lysis of the target cells is detected by measuring the release of radioactivity into the cell supernatant. Support protocols describe procedures for preparing anti-target cell antiserum and (51)Cr-labeled target cells. JF - Current protocols in immunology AU - Nelson, D L AU - Kurman, C C AU - Serbousek, D E AD - National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 7 KW - Chromium Compounds KW - 0 KW - chromic oxide KW - X5Z09SU859 KW - Index Medicus KW - Humans KW - Cytotoxicity Tests, Immunologic -- methods KW - Lymphocytes -- immunology KW - Chromium Compounds -- chemistry KW - Antibody-Dependent Cell Cytotoxicity -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71445420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+immunology&rft.atitle=51Cr+release+assay+of+antibody-dependent+cell-mediated+cytotoxicity+%28ADCC%29.&rft.au=Nelson%2C+D+L%3BKurman%2C+C+C%3BSerbousek%2C+D+E&rft.aulast=Nelson&rft.aufirst=D&rft.date=2001-05-01&rft.volume=Chapter+7&rft.issue=&rft.spage=Unit+7.27&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+immunology&rft.issn=1934-368X&rft_id=info:doi/10.1002%2F0471142735.im0727s08 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-09-29 N1 - Date created - 2008-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142735.im0727s08 ER - TY - JOUR T1 - Assay for macrophage-mediated anti-tumor cytotoxicity. AN - 71420056; 18432725 AB - This unit describes a procedure for determining ability of mouse macrophages to lyse tumor cells in vitro. The Basic Protocol outlines a three-stage assay that includes: (1) culture of macrophages (freshly explanted from mice or grown from a cell line) with suspected activating reagents; (2) extensive washing of the cultured macrophages to remove residual reagents, followed by incubation with [(111)In]-labeled tumor cells to allow lysis to occur; and (3) collection of cell-free culture supernatants and measurement of cytolytic activity as a function of (111)In released from tumor cells destroyed by activated macrophages. The Support Protocol outlines a method for radiolabeling tumor cells with [(111)In]oxine. JF - Current protocols in immunology AU - Cox, G W AD - National Cancer Institute, Frederick, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 14 KW - Index Medicus KW - Animals KW - Cytotoxicity Tests, Immunologic KW - Mice KW - Cell Line, Tumor KW - Cell Line KW - Macrophage Activation -- immunology KW - Macrophages -- immunology KW - Neoplasms, Experimental -- immunology KW - Neoplasms, Experimental -- therapy KW - Immunologic Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71420056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+immunology&rft.atitle=Assay+for+macrophage-mediated+anti-tumor+cytotoxicity.&rft.au=Cox%2C+G+W&rft.aulast=Cox&rft.aufirst=G&rft.date=2001-05-01&rft.volume=Chapter+14&rft.issue=&rft.spage=Unit+14.7&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+immunology&rft.issn=1934-368X&rft_id=info:doi/10.1002%2F0471142735.im1407s12 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-06-05 N1 - Date created - 2008-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142735.im1407s12 ER - TY - JOUR T1 - Internet basics. AN - 71409288; 18429152 AB - With the explosion of sequence and structural information available to researchers, the field of bioinformatics is playing an increasingly large role in the study of fundamental biomedical problems. The challenge facing computational biologists will be to aid in gene discovery and in the design of molecular modeling, site-directed mutagenesis, and experiments of other types that can potentially reveal previously unknown relationships with respect to the structure and function of genes and proteins. This challenge becomes particularly daunting in light of the vast amount of data that has been produced by the Human Genome Project and other systematic sequencing efforts to date. This unit begins with a review of the Internet and its terminology, also discussing major classes of Internet protocols, without becoming overly engaged in the engineering minutiae underlying these protocols. Matters of connectivity, ranging from simple modem connections to digital subscriber lines (DSL) are also discussed. Finally, one of the most common problems that has arisen with the proliferation of Web pages throughout the world is addressed--i.e., finding useful information on the World Wide Web. JF - Current protocols in protein science AU - Baxevanis, A D AU - Ouellette, B F AD - National Human Genome Research Institute, NIH, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 2 KW - Index Medicus KW - Computer Communication Networks KW - Databases, Protein KW - Information Storage and Retrieval -- methods KW - Modems KW - Sequence Analysis, Protein -- methods KW - Computational Biology -- methods KW - Computational Biology -- instrumentation KW - Sequence Analysis, Protein -- instrumentation KW - Internet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71409288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+protein+science&rft.atitle=Internet+basics.&rft.au=Baxevanis%2C+A+D%3BOuellette%2C+B+F&rft.aulast=Baxevanis&rft.aufirst=A&rft.date=2001-05-01&rft.volume=Chapter+2&rft.issue=&rft.spage=Unit2.4&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+protein+science&rft.issn=1934-3663&rft_id=info:doi/10.1002%2F0471140864.ps0204s20 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-06-16 N1 - Date created - 2008-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471140864.ps0204s20 ER - TY - JOUR T1 - Measurement of polyclonal and antigen-specific cytotoxic T cell function. AN - 71400759; 18432831 AB - Measurement of in vitro cytotoxic function of human T cells can be accomplished by polyclonal stimulation of T cell effectors using anti-CD3 antibody, which stimulates all cytolytic effector cells, or with a specific stimulating antigen. Accordingly, two sets of assays of cytolytic T cell function are described in this unit, one for measuring anti-CD3-mediated cytotoxicity and the other for measuring antigen-specific cytotoxicity. Although the calcein release assay (CARE-LASS) described here is for use with antigen-activated cytotoxic T lymphocytes (CTL) as well as natural killer (NK) or lymphokine-activated killer (LAK) cells, minor changes in the protocols that address polyclonal T cell activation are described that make them suitable for use with calcein-labeled target cells. JF - Current protocols in immunology AU - Biddison, W E AU - Lichtenfels, R AU - Adibzadeh, M AU - Martin, R AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 7 KW - Antigens, CD3 KW - 0 KW - Epitopes, T-Lymphocyte KW - Index Medicus KW - Antigens, CD3 -- immunology KW - Humans KW - Cytotoxicity Tests, Immunologic -- methods KW - T-Lymphocytes, Cytotoxic -- immunology KW - Epitopes, T-Lymphocyte -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71400759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+immunology&rft.atitle=Measurement+of+polyclonal+and+antigen-specific+cytotoxic+T+cell+function.&rft.au=Biddison%2C+W+E%3BLichtenfels%2C+R%3BAdibzadeh%2C+M%3BMartin%2C+R&rft.aulast=Biddison&rft.aufirst=W&rft.date=2001-05-01&rft.volume=Chapter+7&rft.issue=&rft.spage=Unit+7.17&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+immunology&rft.issn=1934-368X&rft_id=info:doi/10.1002%2F0471142735.im0717s17 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-09-29 N1 - Date created - 2008-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142735.im0717s17 ER - TY - JOUR T1 - Culture of substantia nigra neurons. AN - 71400474; 18428467 AB - Primary cultures of nigral tissue are widely used as a model system to assay effects of trophic and toxic agents on dopaminergic neurons. Cultured dopaminergic neurons have been successfully transplanted in animals and led to behavioral improvement in animal models of Parkinson's disease. Cell cultures have also been used to study the development of substantia nigra, allowing investigators to identify early inductive events important for nigral development and to study dopaminergic differentiation and target innervation. This unit provides simple and reliable culture protocols for these applications. The first approach presented is the preparation of dissociated nigral cell cultures, the later steps of which can be used as a simple and efficient assay for testing growth factors. A second approach is the preparation of free-floating roller tube cultures, which may be used as a tool for neural transplantation and to study more complex developmental events. A third approach is the production of organotypic cultures using chicken plasma as a matrix. Organotypic cultures can maintain the in vivo cytoarchitecture of a host region in vitro. JF - Current protocols in neuroscience AU - Studer, L AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 3 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Chickens KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Dopamine -- physiology KW - Female KW - Pregnancy KW - Cell Separation -- methods KW - Neurons -- cytology KW - Neurons -- physiology KW - Cell Culture Techniques -- methods KW - Substantia Nigra -- physiology KW - Substantia Nigra -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71400474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+neuroscience&rft.atitle=Culture+of+substantia+nigra+neurons.&rft.au=Studer%2C+L&rft.aulast=Studer&rft.aufirst=L&rft.date=2001-05-01&rft.volume=Chapter+3&rft.issue=&rft.spage=Unit+3.3&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+neuroscience&rft.issn=1934-8576&rft_id=info:doi/10.1002%2F0471142301.ns0303s00 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-06-19 N1 - Date created - 2008-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142301.ns0303s00 ER - TY - JOUR T1 - In vitro motility assay to study translocation of actin by myosin. AN - 71399471; 18228321 AB - A basic property of myosin is its ability to interact with and translocate actin. This unit describes an in vitro motility assay that can be used to study the translocation, or sliding, of actin filaments by myosin bound to a coverslip. The assay makes use of the ability to image single F-actin filaments labeled with rhodamine phalloidin, a high-affinity fluorescent ligand using fluorescence microscopy. The system is fast, easy to set up and maintain, uses only small amounts of protein, and yields quantitative results. JF - Current protocols in cell biology AU - Sellers, J R AD - National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 13 KW - Actins KW - 0 KW - Rhodamines KW - rhodamine-phalloidin KW - Phalloidine KW - 17466-45-4 KW - Myosins KW - EC 3.6.4.1 KW - Index Medicus KW - Animals KW - Humans KW - Phalloidine -- analogs & derivatives KW - Staining and Labeling -- methods KW - Microscopy, Fluorescence -- methods KW - Protein Transport -- physiology KW - Actins -- physiology KW - Myosins -- physiology KW - Actin Cytoskeleton -- physiology KW - Actin Cytoskeleton -- ultrastructure KW - Cell Movement -- physiology KW - Myosins -- ultrastructure KW - Actins -- ultrastructure KW - Cell Migration Assays -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71399471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+cell+biology&rft.atitle=In+vitro+motility+assay+to+study+translocation+of+actin+by+myosin.&rft.au=Sellers%2C+J+R&rft.aulast=Sellers&rft.aufirst=J&rft.date=2001-05-01&rft.volume=Chapter+13&rft.issue=&rft.spage=Unit+13.2&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+cell+biology&rft.issn=1934-2616&rft_id=info:doi/10.1002%2F0471143030.cb1302s00 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-02-28 N1 - Date created - 2008-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471143030.cb1302s00 ER - TY - JOUR T1 - Internet basics for biologists. AN - 71389793; 18428226 AB - With the explosion of sequence and structural information available to researchers, the field of bioinformatics is playing an increasingly large role in the study of fundamental biomedical problems. The challenge facing computational biologists will be to aid in gene discovery and in the design of molecular modeling, site-directed mutagenesis, and experiments of other types that can potentially reveal previously unknown relationships with respect to the structure and function of genes and proteins. This appendix begins with a review of the Internet and its terminology, also discussing major classes of Internet protocols, without becoming overly engaged in the engineering minutiae underlying these protocols. This appendix also discusses matters of connectivity, ranging from simple modem connections to digital subscriber lines (DSL). Finally, one of the most common problems that has arisen with the proliferation of Web pages throughout the worldWith the explosion of sequence and structural information available to researchers, the field of bioinformatics is playing. JF - Current protocols in human genetics AU - Baxevanis, A D AU - Ouellette, B F AD - National Human Genome Research Institute, NIH, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Appendix 3 KW - Index Medicus KW - Humans KW - Genetics, Medical KW - Computational Biology KW - Internet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71389793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+human+genetics&rft.atitle=Internet+basics+for+biologists.&rft.au=Baxevanis%2C+A+D%3BOuellette%2C+B+F&rft.aulast=Baxevanis&rft.aufirst=A&rft.date=2001-05-01&rft.volume=Appendix+3&rft.issue=&rft.spage=Appendix+3J&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+human+genetics&rft.issn=1934-8258&rft_id=info:doi/10.1002%2F0471142905.hga03js24 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-05-22 N1 - Date created - 2008-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142905.hga03js24 ER - TY - JOUR T1 - Use of protein folding reagents. AN - 71388615; 18429069 AB - The reagents and methods for purification of the denaturants guanidine hydrochloride (guanidine-HCl) and urea are described. Sulfhydryl reagents (reducing agents) and "oxido-shuffling" (or oxidative regeneration) systems are also discussed. JF - Current protocols in protein science AU - Wingfield, P T AD - National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Appendix 3 KW - Oxidants KW - 0 KW - Reducing Agents KW - Sulfhydryl Reagents KW - Mercaptoethanol KW - 60-24-2 KW - Urea KW - 8W8T17847W KW - Glutathione KW - GAN16C9B8O KW - Guanidine KW - JU58VJ6Y3B KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - Protein Denaturation KW - Protein Folding KW - Urea -- isolation & purification KW - Guanidine -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71388615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+protein+science&rft.atitle=Use+of+protein+folding+reagents.&rft.au=Wingfield%2C+P+T&rft.aulast=Wingfield&rft.aufirst=P&rft.date=2001-05-01&rft.volume=Appendix+3&rft.issue=&rft.spage=Appendix+3A&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+protein+science&rft.issn=1934-3663&rft_id=info:doi/10.1002%2F0471140864.psa03as00 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-05-09 N1 - Date created - 2008-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471140864.psa03as00 ER - TY - JOUR T1 - Preclinical models of Parkinson's disease. AN - 71386418; 18428552 AB - Parkinson's disease is a neurodegenerative disease in which pigmented midbrain neurons progressively die producing a dopamine (DA) deficit in the striatum which manifests as an akinetic movement disorder. Experimentally induced striatal DA depletion in animals is a valid model of parkinsonism. The capacity of certain substances to damage catecholaminergic neurones has been used for a long time to produce DA deficiency in animals. This unit focuses on methods for inducing parkinsonism using the neurotoxins MPTP and 6-hydroxy dopamine and methods for evaluating the animals. Other models are briefly reviewed. JF - Current protocols in neuroscience AU - Bankiewicz, K S AU - Sanchez-Pernaute, R AU - Oiwa, Y AU - Kohutnicka, M AU - Cummins, A AU - Eberling, J AD - National Institute of Neurological Disorders and Stroke (NIH), Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 9 KW - Neurotoxins KW - 0 KW - Levodopa KW - 46627O600J KW - Oxidopamine KW - 8HW4YBZ748 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Severity of Illness Index KW - Animals KW - Macaca fascicularis KW - Oxidopamine -- administration & dosage KW - Injections, Intra-Arterial -- methods KW - Mice KW - Primates KW - Neurotoxins -- toxicity KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- administration & dosage KW - MPTP Poisoning -- physiopathology KW - Rats KW - Levodopa -- pharmacology KW - Rats, Sprague-Dawley KW - Injections, Intravenous -- methods KW - Oxidopamine -- toxicity KW - Callithrix KW - Mice, Inbred C57BL KW - Macaca mulatta KW - Motor Activity -- drug effects KW - Species Specificity KW - Parkinsonian Disorders -- physiopathology KW - Parkinsonian Disorders -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71386418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+neuroscience&rft.atitle=Preclinical+models+of+Parkinson%27s+disease.&rft.au=Bankiewicz%2C+K+S%3BSanchez-Pernaute%2C+R%3BOiwa%2C+Y%3BKohutnicka%2C+M%3BCummins%2C+A%3BEberling%2C+J&rft.aulast=Bankiewicz&rft.aufirst=K&rft.date=2001-05-01&rft.volume=Chapter+9&rft.issue=&rft.spage=Unit9.4&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+neuroscience&rft.issn=1934-8576&rft_id=info:doi/10.1002%2F0471142301.ns0904s09 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-05-13 N1 - Date created - 2008-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142301.ns0904s09 ER - TY - JOUR T1 - Oligonucleotide-directed mutagenesis without phenotypic selection. AN - 71385263; 18265272 AB - A DNA sequence can be specifically altered by synthesizing the desired sequence change within an oligonucleotide, and then converting this into a biologically active circular DNA strand by using the oligonucleotide to prime in vitro synthesis on a single-stranded circular template. This protocol uses a DNA template containing a small number of uracil residues in place of thymine. Use of the uracil-containing template allows rapid and efficient recovery of mutants; in principle this same template can be applied to most of the other mutagenesis protocols in use. JF - Current protocols in molecular biology AU - Kunkel, T A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 VL - Chapter 8 KW - Index Medicus KW - Point Mutation KW - Selection, Genetic KW - Mutagenesis, Insertional KW - Sequence Deletion KW - Genetic Techniques KW - Mutagenesis, Site-Directed -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71385263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+molecular+biology&rft.atitle=Oligonucleotide-directed+mutagenesis+without+phenotypic+selection.&rft.au=Kunkel%2C+T+A&rft.aulast=Kunkel&rft.aufirst=T&rft.date=2001-05-01&rft.volume=Chapter+8&rft.issue=&rft.spage=Unit8.1&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+molecular+biology&rft.issn=1934-3647&rft_id=info:doi/10.1002%2F0471142727.mb0801s13 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-02-29 N1 - Date created - 2008-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471142727.mb0801s13 ER - TY - JOUR T1 - Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion in the treatment of recurrent epithelial ovarian cancer: a phase II clinical study. AN - 71125248; 11504363 AB - The optimal salvage therapy for recurrent ovarian carcinoma has not been clearly established. Response to second-line chemotherapy is low, with a short median survival (8.8-15 months). We investigated the effect of an aggressive approach consisting of surgery followed by intraperitoneal drug delivery and local hyperthermia. In a phase II clinical study, 27 patients with advanced/recurrent ovarian carcinoma were treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Median patient age was 53 years (range, 30-67) and mean follow-up was 17.4 months (range, 0.3-36.0). Patients had been surgically staged and heavily pretreated with cisplatin-based, taxol-based or taxol/platinum-containing regimens. Nineteen (70%) patients were cytoreduced to minimal residual disease <2.5 mm. The intraperitoneal hyperthermic perfusion was performed with the closed abdomen technique, using a preheated polysaline perfusate containing cisplatin (25 mg/m2/L) + mitomycin C (3.3 mg/m2/L) through a heart-lung pump (mean flow of 700 mL/min) for 60 min in the hyperthermic phase (42.5 degrees C). Two-year overall survival was 55%. Median times to overall progression and local progression were 16 months and 21.8 months, respectively. Variables that affected the overall survival or time to progression were as follows: residual disease (P = 0.00025), patient age (P = 0.04), and lag time between diagnosis and cytoreductive surgery + intraperitoneal hyperthermic perfusion (P = 0.04). Treatment-related morbidity, mortality and acute toxicity (grade II-III) rates were 11%, 4% and 11%, respectively. Eight (89%) of 9 patients had ascites resolution. Our results suggest that cytoreductive surgery + intraperitoneal hyperthermic perfusion is a well-tolerated, feasible and promising alternative in the management of selected patients with recurrent ovarian cancer, but further randomized controlled studies are needed in order to confirm our findings. JF - Tumori AU - Deraco, M AU - Rossi, C R AU - Pennacchioli, E AU - Guadagni, S AU - Somers, D C AU - Santoro, N AU - Raspagliesi, F AU - Kusamura, S AU - Vaglini, M AD - Department of Surgery, National Cancer Institute, Milan, Italy. marcelloderaco@hotmail.com PY - 2001 SP - 120 EP - 126 VL - 87 IS - 3 SN - 0300-8916, 0300-8916 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - Mitomycin KW - 50SG953SK6 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Peritoneum KW - Aged KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Mitomycin -- administration & dosage KW - Cisplatin -- administration & dosage KW - Feasibility Studies KW - Adult KW - Treatment Outcome KW - Follow-Up Studies KW - Middle Aged KW - Biomarkers, Tumor -- blood KW - Female KW - Survival Analysis KW - Carcinoma -- surgery KW - Neoplasm Recurrence, Local -- drug therapy KW - Carcinoma -- drug therapy KW - Hyperthermia, Induced KW - Ovarian Neoplasms -- surgery KW - Carcinoma -- immunology KW - Neoplasm Recurrence, Local -- surgery KW - Antineoplastic Agents -- therapeutic use KW - Ovarian Neoplasms -- immunology KW - Ovarian Neoplasms -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71125248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Cytoreductive+surgery+followed+by+intraperitoneal+hyperthermic+perfusion+in+the+treatment+of+recurrent+epithelial+ovarian+cancer%3A+a+phase+II+clinical+study.&rft.au=Deraco%2C+M%3BRossi%2C+C+R%3BPennacchioli%2C+E%3BGuadagni%2C+S%3BSomers%2C+D+C%3BSantoro%2C+N%3BRaspagliesi%2C+F%3BKusamura%2C+S%3BVaglini%2C+M&rft.aulast=Deraco&rft.aufirst=M&rft.date=2001-05-01&rft.volume=87&rft.issue=3&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic ethanol intoxication enhances the production of cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2 by hepatocytes after human immunodeficiency virus-1 glycoprotein 120 vaccination. AN - 71125094; 11524180 AB - Chemokines are implicated in the pathogenesis of alcoholic liver disease and human immunodeficiency virus-1 (HIV-1) infection. Thus, this work examined the regulation of chemokines --i.e., cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2)--produced by hepatocytes after HIV-1 glycoprotein 120 (gp120) vaccination in Wistar rats fed with ethanol for 30 weeks. HIV-1 gp120 in complete Freund's adjuvant was given by intrainguinal route at a dose of 5 g/kg, followed by two booster shots in incomplete Freund's adjuvant at a weekly interval. Samples were taken 1 week after the last injection was given. Results show that anti-HIV-1 gp120 antibody titer was suppressed by 40% in the ethanol-fed rats, compared with findings in the parallel controls. However, serum CINC and MIP-2 levels were more elevated in the ethanol-fed rats than in the pair-fed group. The likely sources of these chemokines are the hepatocytes. After HIV-1 gp120 treatment, isolated hepatocytes obtained from the ethanol-fed group produced more CINC and MIP-2 than did those of pair-fed rats. Concomitantly, mRNA expression for these two chemokines and hepatic sequestration of neutrophils were upregulated. Ethanol feeding alone suppressed chemokine release, but it did not alter mRNA expression in isolated hepatocytes. Administration of Freund's adjuvant (without HIV-1 gp120) did not induce chemokine release in vivo and did not prime isolated hepatocytes for enhanced chemokine production in vitro. These results show that chronic ethanol intoxication affects the ability of the host to respond to HIV-1 gp120 vaccination. JF - Alcohol (Fayetteville, N.Y.) AU - Bautista, A P AU - Wang, E AD - Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA. abauti@lsuhsc.edu Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 35 EP - 44 VL - 24 IS - 1 SN - 0741-8329, 0741-8329 KW - AIDS Vaccines KW - 0 KW - CXCL1 protein, human KW - Chemokine CXCL1 KW - Chemokine CXCL2 KW - Chemokines, CXC KW - Chemotactic Factors KW - Cxcl1 protein, rat KW - Cxcl2 protein, rat KW - Growth Substances KW - HIV Envelope Protein gp120 KW - Intercellular Signaling Peptides and Proteins KW - Monokines KW - Index Medicus KW - Rats KW - Animals KW - Cells, Cultured KW - Up-Regulation -- drug effects KW - Rats, Wistar KW - Up-Regulation -- immunology KW - Male KW - AIDS Vaccines -- administration & dosage KW - HIV-1 -- immunology KW - Hepatocytes -- drug effects KW - AIDS Vaccines -- immunology KW - Alcoholism -- metabolism KW - HIV Envelope Protein gp120 -- immunology KW - Chemotactic Factors -- biosynthesis KW - Hepatocytes -- immunology KW - Growth Substances -- biosynthesis KW - Alcoholism -- immunology KW - Monokines -- biosynthesis KW - Hepatocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71125094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Chronic+ethanol+intoxication+enhances+the+production+of+cytokine-induced+neutrophil+chemoattractant+and+macrophage+inflammatory+protein-2+by+hepatocytes+after+human+immunodeficiency+virus-1+glycoprotein+120+vaccination.&rft.au=Bautista%2C+A+P%3BWang%2C+E&rft.aulast=Bautista&rft.aufirst=A&rft.date=2001-05-01&rft.volume=24&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Pleural mesothelioma in women in the Veneto Region who used to work as rag sorters for textile recycling and paper production]. TT - Mesoteliomi pleurici insorti in donne, residenti in Veneto, addette alla cernita di stracci presso "robe vecchie" e cartiere. AN - 71118052; 11515151 AB - The paper reports 9 cases of mesothelioma diagnosed by means of histology or cytology that were observed among women resident in the Veneto Region, Northern Italy, whose only activity that could involve exposure to asbestos was as rag sorter. These cases are part of a group of about 260 subjects with mesothelioma whose entire working and residential history has been collected. The women worked as rag sorters between the 1940's and 1960's in textile recycling (8 cases) or (one case) at a paper mill where cotton was used for paper production. The work as rag sorter helps to explain the high proportion of mesotheliomas among women with an occupational exposure to asbestos. JF - La Medicina del lavoro AU - Merler, E AU - Gioffrè, F AU - Rozio, L AU - Bizzotto, R AU - Mion, M AU - Sarto, F AD - Servizio per la Prevenzione Igiene e Sicurezza nei Luoghi Lavoro, Unità Locale Socio Sanitaria n. 16, Padova. spisal@ulss16.padova.it PY - 2001 SP - 181 EP - 186 VL - 92 IS - 3 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Paper KW - Textiles KW - Humans KW - Aged KW - Middle Aged KW - Time Factors KW - Italy KW - Female KW - Mesothelioma -- epidemiology KW - Pleural Neoplasms -- epidemiology KW - Pleural Neoplasms -- pathology KW - Occupational Diseases -- pathology KW - Mesothelioma -- pathology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71118052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BPleural+mesothelioma+in+women+in+the+Veneto+Region+who+used+to+work+as+rag+sorters+for+textile+recycling+and+paper+production%5D.&rft.au=Merler%2C+E%3BGioffr%C3%A8%2C+F%3BRozio%2C+L%3BBizzotto%2C+R%3BMion%2C+M%3BSarto%2C+F&rft.aulast=Merler&rft.aufirst=E&rft.date=2001-05-01&rft.volume=92&rft.issue=3&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-01 N1 - Date created - 2001-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indomethacin reduces lung adenoma number in A/J mice. AN - 71075550; 11497255 AB - The effects of indomethacin on A/J mice were investigated. The non-steroidal antiinflammatory drug (NSAID) indomethacin reduced significantly the number of lung adenomas 3, 4 or 8 months after urethane injection by 28, 30 and 29% respectively. The density of apoptotic cell bodies increased 2.9-fold in the lung adenomas of A/J mice treated with indomethacin. By immunocytochemistry, COX-2 immunoreactivity was present in the cytosol of lung adenomas, and in epithelial cells lining the bronchioli and bronchus as well as type 2 alveolar cells. COX-1 immunostaining was similar to that of COX-2 in the lungs of urethane-injected mice treated with or without indomethacin. By RT-PCR, COX-1 and COX-2 PCR products were present in mouse lung adenomas, alveoli and bronchioli. These results suggest that indomethacin may inhibit COX-1 and COX-2 in the A/J mouse lung resulting in reduced adenoma formation. JF - Anticancer research AU - Moody, T W AU - Leyton, J AU - Zakowicz, H AU - Hida, T AU - Kang, Y AU - Jakowlew, S AU - You, L AU - Ozbun, L AU - Zia, H AU - Youngberg, J AU - Malkinson, A AD - Cell and Cancer Biology Department Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov PY - 2001 SP - 1749 EP - 1755 VL - 21 IS - 3B SN - 0250-7005, 0250-7005 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Carcinogens KW - Isoenzymes KW - Membrane Proteins KW - RNA, Messenger KW - Urethane KW - 3IN71E75Z5 KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - PTGS1 protein, human KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Apoptosis KW - Humans KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Epithelial Cells -- metabolism KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Isoenzymes -- biosynthesis KW - Bronchi -- metabolism KW - Time Factors KW - Immunohistochemistry KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Female KW - Adenoma -- drug therapy KW - Lung Neoplasms -- drug therapy KW - Adenoma -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Indomethacin -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71075550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Indomethacin+reduces+lung+adenoma+number+in+A%2FJ+mice.&rft.au=Moody%2C+T+W%3BLeyton%2C+J%3BZakowicz%2C+H%3BHida%2C+T%3BKang%2C+Y%3BJakowlew%2C+S%3BYou%2C+L%3BOzbun%2C+L%3BZia%2C+H%3BYoungberg%2C+J%3BMalkinson%2C+A&rft.aulast=Moody&rft.aufirst=T&rft.date=2001-05-01&rft.volume=21&rft.issue=3B&rft.spage=1749&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - From adjuvant therapy to breast cancer prevention: BCPT and STAR. AN - 71028990; 11469927 AB - The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women > or = 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p or = 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events. JF - The breast journal AU - Dunn, B K AU - Ford, L G AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. PY - 2001 SP - 144 EP - 157 VL - 7 IS - 3 SN - 1075-122X, 1075-122X KW - Antineoplastic Agents, Hormonal KW - 0 KW - Selective Estrogen Receptor Modulators KW - Tamoxifen KW - 094ZI81Y45 KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Primary Prevention KW - Humans KW - Treatment Outcome KW - Female KW - Chemotherapy, Adjuvant KW - Risk Assessment KW - Prevalence KW - Breast Neoplasms -- drug therapy KW - Tamoxifen -- therapeutic use KW - Selective Estrogen Receptor Modulators -- therapeutic use KW - Raloxifene Hydrochloride -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71028990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+breast+journal&rft.atitle=From+adjuvant+therapy+to+breast+cancer+prevention%3A+BCPT+and+STAR.&rft.au=Dunn%2C+B+K%3BFord%2C+L+G&rft.aulast=Dunn&rft.aufirst=B&rft.date=2001-05-01&rft.volume=7&rft.issue=3&rft.spage=144&rft.isbn=&rft.btitle=&rft.title=The+breast+journal&rft.issn=1075122X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-29 N1 - Date created - 2001-07-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Breast J. 2001 May-Jun;7(3):143 [11469926] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to diesel engine emissions and risk of cancer in Swedish men and women. AN - 71016041; 11456233 AB - To investigate the risk of cancer among workers exposed to diesel emissions in a large record-linkage study from Sweden. The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971-1989, by occupation and industry of employment as reported in the 1960 and 1970 censuses. After excluding farmers, we classified job and industry titles according to estimated probability and intensity of exposure to diesel emissions. Exposed men in the 1960 census contributed over 7,400,000 person-years, and exposed women contributed over 240,000. We compared them to the remainder of the employed population, using indirect standardization and multivariate Poisson regression analysis. Men exposed in the 1960 census experienced an increased risk of lung cancer: the relative risks (RRs) were 0.95 (95% confidence interval [CI] 0.9-1.0), 1.1 (1.1-1.2) and 1.3 (1.3-1.4) for low, medium, and high intensity of exposure. Corresponding results for probability of exposure were 1.1 (1.0-1.1), 0.9 (0.86-0.94) and 1.2 (1.1-1.2). The risk was higher for squamous cell carcinoma of the lung than for other histological types. Results in women were not suggestive of an effect (RR in the category of medium or high intensity of exposure 1.1, 95% CI 0.6-1.8). A small but significant increase in risk of cancers of the stomach (SIR 1.06), pancreas (SIR 1.05), larynx (SIR 1.09), and the kidney (SIR 1.06) was present among men exposed to diesel emissions, without a clear trend according to either probability or intensity of exposure. The SIR among women was non-significantly increased for stomach, pancreatic, and laryngeal cancers, but not for kidney cancer. Furthermore, a significantly increased risk of oral/pharyngeal (SIR 1.64) and cervical (SIR 1.48) cancers was present among women, with a suggestion of a dose-response relationship. There was no increased risk of bladder cancer in either gender. The results of this study provide evidence of a positive exposure-response relationship between exposure to diesel emissions and lung cancer risk among men. The positive results for other neoplasms, such as stomach, pancreatic, oral/pharyngeal, and cervical cancers, cannot be attributed to diesel exposure, but they deserve attention in future investigations. JF - Cancer causes & control : CCC AU - Boffetta, P AU - Dosemeci, M AU - Gridley, G AU - Bath, H AU - Moradi, T AU - Silverman, D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. boffetta@iarc.fr Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 365 EP - 374 VL - 12 IS - 4 SN - 0957-5243, 0957-5243 KW - Vehicle Emissions KW - 0 KW - Index Medicus KW - Registries KW - Risk KW - Humans KW - Cohort Studies KW - Adult KW - Sweden -- epidemiology KW - Incidence KW - Sex Distribution KW - Male KW - Female KW - Multivariate Analysis KW - Age Distribution KW - Occupational Diseases -- etiology KW - Neoplasms -- epidemiology KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- epidemiology KW - Neoplasms -- etiology KW - Vehicle Emissions -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71016041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Occupational+exposure+to+diesel+engine+emissions+and+risk+of+cancer+in+Swedish+men+and+women.&rft.au=Boffetta%2C+P%3BDosemeci%2C+M%3BGridley%2C+G%3BBath%2C+H%3BMoradi%2C+T%3BSilverman%2C+D&rft.aulast=Boffetta&rft.aufirst=P&rft.date=2001-05-01&rft.volume=12&rft.issue=4&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does a reduced sensitivity to bitter taste increase the risk of becoming nicotine addicted? AN - 70987243; 11436931 AB - Cigarette smoking appears to be on the increase in adolescents. The initiation of regular smoking nearly always begins before adulthood. It is therefore crucial to find ways of identifying those children most vulnerable to nicotine addiction and prioritizing them for preventive measures. We hypothesized that individuals who, in a simple taste test, perceive phenylthiocarbamide (PTC) as bitter may find the taste of cigarettes aversively bitter and could therefore have a reduced vulnerability to nicotine addiction compared to nontasters, who would be the group at greater risk of addiction. We studied 242 Plains American Indians, 136 women and 106 men aged 18-59 years, and found that (allowing for gender differences and the possible direct effects of smoking on taste) the proportion of PTC nontasters to tasters in smokers, even light smokers, was significantly greater than in both nonsmokers and social smokers (chi2= 15.875, 4 df; P=.003), suggesting that nontasters, who are not aversive to the bitter taste of cigarettes, may be more at risk for heavy smoking and therefore more vulnerable to nicotine addiction. JF - Addictive behaviors AU - Enoch, M A AU - Harris, C R AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8110, USA. maenoch@dicbr.niaaa.nih.gov PY - 2001 SP - 399 EP - 404 VL - 26 IS - 3 SN - 0306-4603, 0306-4603 KW - Phenylthiourea KW - 6F82C6Q54C KW - Index Medicus KW - Risk KW - Indians, North American KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Prevalence KW - Smoking -- physiopathology KW - Tobacco Use Disorder -- physiopathology KW - Taste -- drug effects KW - Tobacco Use Disorder -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70987243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=Does+a+reduced+sensitivity+to+bitter+taste+increase+the+risk+of+becoming+nicotine+addicted%3F&rft.au=Enoch%2C+M+A%3BHarris%2C+C+R%3BGoldman%2C+D&rft.aulast=Enoch&rft.aufirst=M&rft.date=2001-05-01&rft.volume=26&rft.issue=3&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)? AN - 70922536; 11401753 AB - Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, has been listed by the International Agency for Research on Cancer (IARC) and by the National Toxicology Program as a possible or reasonably anticipated human carcinogen because it induces dose-related increases in liver tumors in both sexes of rats and mice. Recently, the suggestion has been advanced that DEHP should be considered unlikely to be a human carcinogen because it is claimed that the carcinogenic effects of this agent in rodents are due to peroxisome proliferation and that humans are nonresponsive to this process. An IARC working group recently downgraded DEHP to "not classifiable as to its carcinogenicity to humans" because they concluded that DEHP produces liver tumors in rats and mice by a mechanism involving peroxisome proliferation, which they considered to be not relevant to humans. The literature review presented in this commentary reveals that, although our knowledge of the mechanism of peroxisome proliferation has advanced greatly over the past 10 years, our understanding of the mechanism(s) of carcinogenicty of peroxisome proliferators remains incomplete. Most important is that published studies have not established peroxisome proliferation per se as an obligatory pathway in the carcinogenicity of DEHP. No epidemiologic studies have been reported on the potential carcinogenicity of DEHP, and cancer epidemiologic studies of hypolipidemic fibrate drugs (peroxisome proliferators) are inconclusive. Most of the pleiotropic effects of peroxisome proliferators are mediated by the peroxisome proliferator activated receptor (PPAR), a ligand-activated transcription factor that is expressed at lower levels in humans than in rats and mice. In spite of this species difference in PPAR expression, hypolipidemic fibrates have been shown to induce hypolipidemia in humans and to modulate gene expression (e.g., genes regulating lipid homeostasis) in human hepatocytes by PPAR activation. Thus, humans are responsive to agents that induce peroxisome proliferation in rats and mice. Because peroxisome proliferators can affect multiple signaling pathways by transcriptional activation of PPAR-regulated genes, it is likely that alterations in specific regulated pathways (e.g., suppression of apoptosis, protooncogene expression) are involved in tumor induction by peroxisome proliferators. In addition, because DEHP also induces biological effects that occur independently of peroxisome proliferation (e.g., morphologic cell transformation and decreased levels of gap junction intercellular communication), it is possible that some of these responses also contribute to the carcinogenicity of this chemical. Last, species differences in tissue expression of PPARs indicate that it may not be appropriate to expect exact site correspondence for potential PPAR-mediated effects induced by peroxisome proliferators in animals and humans. Because peroxisome proliferation has not been established as an obligatory step in the carcinogenicity of DEHP, the contention that DEHP poses no carcinogenic risk to humans because of species differences in peroxisome proliferation should be viewed as an unvalidated hypothesis. JF - Environmental health perspectives AU - Melnick, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. melnickr@niehs.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 437 EP - 442 VL - 109 IS - 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Peroxisome Proliferators KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Index Medicus KW - Rats KW - Animals KW - Apoptosis KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Humans KW - Cell Division -- drug effects KW - Carcinogens -- toxicity KW - Carcinogenicity Tests KW - Mice KW - Species Specificity KW - Signal Transduction KW - Risk Assessment KW - Peroxisome Proliferators -- toxicity KW - Diethylhexyl Phthalate -- toxicity KW - Liver Neoplasms -- chemically induced KW - Peroxisome Proliferators -- pharmacology KW - Diethylhexyl Phthalate -- pharmacology KW - Peroxisomes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70922536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Is+peroxisome+proliferation+an+obligatory+precursor+step+in+the+carcinogenicity+of+di%282-ethylhexyl%29phthalate+%28DEHP%29%3F&rft.au=Melnick%2C+R+L&rft.aulast=Melnick&rft.aufirst=R&rft.date=2001-05-01&rft.volume=109&rft.issue=5&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-06-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Carcinogenesis. 1997 Aug;18(8):1453-6 [9276615] Biochimie. 1997 Feb-Mar;79(2-3):139-44 [9209711] Carcinogenesis. 1997 Nov;18(11):2029-33 [9395198] Teratology. 1997 Nov;56(5):311-6 [9451755] Mol Pharmacol. 1998 Jan;53(1):14-22 [9443928] Carcinogenesis. 1998 Jan;19(1):43-8 [9472691] Crit Rev Toxicol. 1998 Jan;28(1):1-33 [9493760] Arch Environ Contam Toxicol. 1998 Apr;34(3):306-10 [9504980] Arch Toxicol. 1998 Feb;72(3):169-77 [9520140] Toxicol Pathol. 1998 Mar-Apr;26(2):240-6 [9547862] Biochem J. 1998 Jun 15;332 ( Pt 3):689-93 [9620871] Toxicol Appl Pharmacol. 1998 Jun;150(2):277-86 [9653058] Arch Toxicol. 1998 Dec;72(12):777-83 [9950074] Carcinogenesis. 1999 Mar;20(3):369-72 [10190548] Pharmacol Ther. 1999 Apr;82(1):63-70 [10341357] Endocrinology. 1999 Jul;140(7):2968-75 [10385388] Regul Toxicol Pharmacol. 1999 Jun;29(3):327-57 [10388618] Toxicol Appl Pharmacol. 1999 Oct 1;160(1):21-32 [10502499] Carcinogenesis. 1996 Aug;17(8):1623-32 [8761418] Crit Rev Toxicol. 1996 Jun;26(4):365-481 [8817083] Ann N Y Acad Sci. 1996 Dec 27;804:252-65 [8993548] Mol Cell Endocrinol. 1997 May 16;129(2):229-35 [9202406] J Biol Chem. 1997 Oct 24;272(43):27307-12 [9341179] Toxicol Appl Pharmacol. 1999 Dec 1;161(2):209-18 [10581215] Arch Toxicol. 1999 Nov;73(8-9):451-6 [10650916] Arch Toxicol. 2000 Apr;74(2):85-91 [10839475] Toxicol Appl Pharmacol. 1975 May;32(2):355-67 [168667] Nature. 1980 Jan 24;283(5745):397-8 [6766207] J Toxicol Environ Health. 1982 Oct-Nov;10(4-5):797-815 [7161829] Toxicology. 1985 Jan;34(1):13-27 [3969678] Cancer Res. 1988 Dec 1;48(23):6739-44 [3180084] Nature. 1990 Oct 18;347(6294):645-50 [2129546] Toxicol Appl Pharmacol. 1990 Dec;106(3):509-17 [2260097] Biochem Biophys Res Commun. 1990 Dec 31;173(3):855-61 [2268348] Carcinogenesis. 1991 Mar;12(3):469-73 [1849052] FASEB J. 1992 Jun;6(9):2698-706 [1612294] Nature. 1992 Aug 27;358(6389):771-4 [1324435] Fundam Appl Toxicol. 1992 Nov;19(4):590-7 [1426718] Carcinogenesis. 1993 Jan;14(1):145-9 [8425263] Carcinogenesis. 1993 Feb;14(2):251-7 [8435866] Carcinogenesis. 1993 Apr;14(4):611-8 [8472324] Biochemistry. 1993 Jun 1;32(21):5598-604 [7684926] Toxicol Ind Health. 1993 May-Jun;9(3):415-38 [8367884] J Steroid Biochem Mol Biol. 1994 Nov;51(3-4):157-66 [7981125] Hum Exp Toxicol. 1994 Nov;13 Suppl 2:S1-117 [7857698] J Clin Invest. 1995 Aug;96(2):741-50 [7635967] JAMA. 1996 Jan 3;275(1):55-60 [8531288] J Biol Chem. 1996 Jan 26;271(4):2147-55 [8567672] Biochim Biophys Acta. 1996 Jul 26;1302(2):93-109 [8695669] Comment In: Environ Health Perspect. 2001 Oct;109(10):A462-4 [11675276] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma drug levels compared with DNA incorporation of 3'-azido-3'-deoxythymidine (AZT) in adult cynomolgus (Macaca fascicularis) monkeys. AN - 70908839; 11393173 AB - Zidovudine (3'-azido-3'-deoxythymidine, AZT), widely used for the therapy of the Human Immunodeficiency Virus-1 (HIV-1), is a nucleoside analog of thymidine that becomes phosphorylated and incorporated into nuclear and mitochondrial DNA. Levels of AZT incorporation into DNA of humans, monkeys, and mice are highly variable and suggest interindividual variability in phosphorylation pathways. In addition, studies in rhesus monkeys (1) have shown a lack of correlation between levels of unbound AZT in plasma and tissue AZT-DNA. However, the correlation between plasma AZT and tissue AZT-DNA has not been previously examined in the same primate. Here we examine the relationship between AZT-DNA incorporation in leukocytes and multiple organs, and levels of the drug circulating in plasma of adult female cynomolgus (Macaca fascicularis) monkeys. Three monkeys were dosed with 40.0 mg of AZT/day for 30 days by naso-gastric intubation. The average daily dose of 9.9 mg of AZT/kg/body wt was similar to the approximately 8.6 mg of AZT/kg/body wt (600 mg/day) given to adult HIV-1-infected patients. In all three monkeys, at the time of sampling, values for AZT concentrations in plasma were similar and values for AZT incorporation into leukocyte DNA (86.1, 100.0, and 114.1 molecules of AZT/10(6) nucleotides) were also similar. AZT-DNA incorporation was detected in liver, uterus, spleen, and kidney from the three AZT-exposed animals, with values for positive samples ranging from 5.8 to 97.4 molecules of AZT/10(6) nucleotides. In brain cortex and lung DNA from AZT-exposed animals, AZT incorporation was undetectable. The data suggest that organ-specific differences in AZT uptake and/or metabolism may contribute to AZT phosphorylation and subsequent drug incorporation into DNA. In addition, AZT-DNA levels in monkey organs were similar to or lower than values observed in peripheral leukocytes of adult AIDS patients. JF - Experimental biology and medicine (Maywood, N.J.) AU - Olivero, O A AU - Reddy, M K AU - Pietras, S M AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 446 EP - 449 VL - 226 IS - 5 SN - 1535-3702, 1535-3702 KW - Anti-HIV Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Leukocytes -- metabolism KW - Animals KW - Phosphorylation KW - Tissue Distribution KW - Female KW - Biological Availability KW - Macaca fascicularis -- blood KW - Zidovudine -- pharmacokinetics KW - Anti-HIV Agents -- pharmacokinetics KW - Zidovudine -- metabolism KW - Anti-HIV Agents -- metabolism KW - DNA -- metabolism KW - Zidovudine -- blood KW - Anti-HIV Agents -- blood KW - Macaca fascicularis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70908839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.atitle=Plasma+drug+levels+compared+with+DNA+incorporation+of+3%27-azido-3%27-deoxythymidine+%28AZT%29+in+adult+cynomolgus+%28Macaca+fascicularis%29+monkeys.&rft.au=Olivero%2C+O+A%3BReddy%2C+M+K%3BPietras%2C+S+M%3BPoirier%2C+M+C&rft.aulast=Olivero&rft.aufirst=O&rft.date=2001-05-01&rft.volume=226&rft.issue=5&rft.spage=446&rft.isbn=&rft.btitle=&rft.title=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.issn=15353702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fetal alcohol syndrome: an international perspective. AN - 70906241; 11391072 AB - This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Kenneth R. Warren and Faye J. Calhoun. The presentations were (1) Epidemiological research on fetal alcohol syndrome (FAS) in the United States, by Philip A. May; (2) An overview of fetal alcohol syndrome in the Western Cape Province of South Africa, by Denis L. Viljoen and Ting-Kai Li; (3) Diagnostic perspectives of fetal alcohol and tobacco syndromes, by Harumi Tanaka; (4) FAS among pupils of special boarding schools and orphanages in Moscow, Russia, by Galina S. Marinicheva and Luther K. Robinson; and (5) Research on FAS and FAE in Germany: Update and perspectives, by Goetz Mundle. JF - Alcoholism, clinical and experimental research AU - Warren, K R AU - Calhoun, F J AU - May, P A AU - Viljoen, D L AU - Li, T K AU - Tanaka, H AU - Marinicheva, G S AU - Robinson, L K AU - Mundle, G AD - National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland 20892-7003, USA. kwarren@willco.niaaa.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 202S EP - 206S VL - 25 IS - 5 Suppl ISBRA SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Japan -- epidemiology KW - South Africa -- epidemiology KW - Humans KW - Europe -- epidemiology KW - United States -- epidemiology KW - Male KW - Female KW - Pregnancy KW - Fetal Alcohol Spectrum Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70906241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Fetal+alcohol+syndrome%3A+an+international+perspective.&rft.au=Warren%2C+K+R%3BCalhoun%2C+F+J%3BMay%2C+P+A%3BViljoen%2C+D+L%3BLi%2C+T+K%3BTanaka%2C+H%3BMarinicheva%2C+G+S%3BRobinson%2C+L+K%3BMundle%2C+G&rft.aulast=Warren&rft.aufirst=K&rft.date=2001-05-01&rft.volume=25&rft.issue=5+Suppl+ISBRA&rft.spage=202S&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iodine nutrition and the risk from radioactive iodine: a workshop report in the chernobyl long-term follow-up study. AN - 70903283; 11396707 AB - The major fallout of radionuclides from the nuclear power station accident at Chernobyl on 26 April, 1986, occurred in regions of Ukraine and Belarus that are believed to be moderately deficient in dietary iodine. On 17 November, 2000, in conjunction with the Ukraine-Belarus-USA study of developing thyroid disease in a cohort of individuals exposed as children, a workshop was held to review what is known about iodine nutrition in the region, how this might influence the risk of thyroid tumor formation from radioiodine, and whether and how iodine nutrition should be monitored in this long-term project. This report is a summary of the workshop proceedings. Although no precise information about iodine intake in 1986 was found, the prevalence of mild goiter in the region's children suggested iodine deficiency and urinary iodine measurements begun in 1990 indicated that mild to moderate deficiency existed. Increased thyroid iodine uptake and increased thyroid size in 1986 resulting from iodine deficiency would have had counteracting influence on the thyroid radiation dose and knowledge of these parameters is required for dose reconstruction. More problematic is the possible role of iodine deficiency in the years following the accident. Theoretically, the resulting increase in thyroid cellular activity might increase the risk of tumorigenesis but experimental or clinical evidence supporting this hypothesis is meager or absent. Despite this limitation it was considered important to monitor iodine nutrition in the cohort subjects in relation to their place of residence and over time. Methods to accomplish this were discussed. JF - Thyroid : official journal of the American Thyroid Association AU - Robbins, J AU - Dunn, J T AU - Bouville, A AU - Kravchenko, V I AU - Lubin, J AU - Petrenko, S AU - Sullivan, K M AU - Vanmiddlesworth, L AU - Wolff, J AD - National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-2560, USA. jacobr@bdg10.niddk.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 487 EP - 491 VL - 11 IS - 5 SN - 1050-7256, 1050-7256 KW - Iodine Radioisotopes KW - 0 KW - Iodine KW - 9679TC07X4 KW - Index Medicus KW - Ukraine -- epidemiology KW - Thyroid Gland -- pathology KW - Risk Factors KW - Humans KW - Republic of Belarus -- epidemiology KW - Thyroid Neoplasms -- etiology KW - Goiter -- epidemiology KW - Thyroid Gland -- metabolism KW - Goiter -- etiology KW - Nutritional Status KW - Iodine -- administration & dosage KW - Iodine -- urine KW - Iodine -- deficiency KW - Radioactive Hazard Release KW - Iodine Radioisotopes -- adverse effects KW - Iodine Radioisotopes -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70903283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.atitle=Iodine+nutrition+and+the+risk+from+radioactive+iodine%3A+a+workshop+report+in+the+chernobyl+long-term+follow-up+study.&rft.au=Robbins%2C+J%3BDunn%2C+J+T%3BBouville%2C+A%3BKravchenko%2C+V+I%3BLubin%2C+J%3BPetrenko%2C+S%3BSullivan%2C+K+M%3BVanmiddlesworth%2C+L%3BWolff%2C+J&rft.aulast=Robbins&rft.aufirst=J&rft.date=2001-05-01&rft.volume=11&rft.issue=5&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.issn=10507256&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease. AN - 70892258; 11391128 AB - The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning "off"-L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries ("on" without dyskinesia, "on" with dyskinesia, and "off"). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications. JF - Clinical neuropharmacology AU - Metman, L V AU - Gillespie, M AU - Farmer, C AU - Bibbiani, F AU - Konitsiotis, S AU - Morris, M AU - Shill, H AU - Bara-Jimenez, W AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. PY - 2001 SP - 163 EP - 169 VL - 24 IS - 3 SN - 0362-5664, 0362-5664 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agonists KW - Tetrahydronaphthalenes KW - Thiophenes KW - Levodopa KW - 46627O600J KW - rotigotine KW - 5QTR54Z0E1 KW - Index Medicus KW - Administration, Cutaneous KW - Levodopa -- administration & dosage KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Levodopa -- therapeutic use KW - Aged KW - Middle Aged KW - Levodopa -- adverse effects KW - Male KW - Female KW - Antiparkinson Agents -- adverse effects KW - Thiophenes -- adverse effects KW - Tetrahydronaphthalenes -- therapeutic use KW - Antiparkinson Agents -- administration & dosage KW - Antiparkinson Agents -- therapeutic use KW - Dopamine Agonists -- adverse effects KW - Parkinson Disease -- drug therapy KW - Tetrahydronaphthalenes -- administration & dosage KW - Thiophenes -- therapeutic use KW - Dopamine Agonists -- therapeutic use KW - Tetrahydronaphthalenes -- adverse effects KW - Dopamine Agonists -- administration & dosage KW - Thiophenes -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70892258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+neuropharmacology&rft.atitle=Continuous+transdermal+dopaminergic+stimulation+in+advanced+Parkinson%27s+disease.&rft.au=Metman%2C+L+V%3BGillespie%2C+M%3BFarmer%2C+C%3BBibbiani%2C+F%3BKonitsiotis%2C+S%3BMorris%2C+M%3BShill%2C+H%3BBara-Jimenez%2C+W%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Metman&rft.aufirst=L&rft.date=2001-05-01&rft.volume=24&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Clinical+neuropharmacology&rft.issn=03625664&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of myosin heavy chain expression during rat skeletal muscle development in vitro. AN - 70887478; 11359938 AB - Signals that determine fast- and slow-twitch phenotypes of skeletal muscle fibers are thought to stem from depolarization, with concomitant contraction and activation of calcium-dependent pathways. We examined the roles of contraction and activation of calcineurin (CN) in regulation of slow and fast myosin heavy chain (MHC) protein expression during muscle fiber formation in vitro. Myotubes formed from embryonic day 21 rat myoblasts contracted spontaneously, and approximately 10% expressed slow MHC after 12 d in culture, as seen by immunofluorescent staining. Transfection with a constitutively active form of calcineurin (CN*) increased slow MHC by 2.5-fold as determined by Western blot. This effect was attenuated 35% by treatment with tetrodotoxin and 90% by administration of the selective inhibitor of CN, cyclosporin A. Conversely, cyclosporin A alone increased fast MHC by twofold. Cotransfection with VIVIT, a peptide that selectively inhibits calcineurin-induced activation of the nuclear factor of activated T-cells, blocked the effect of CN* on slow MHC by 70% but had no effect on fast MHC. The results suggest that contractile activity-dependent expression of slow MHC is mediated largely through the CN-nuclear factor of activated T-cells pathway, whereas suppression of fast MHC expression may be independent of nuclear factor of activated T-cells. JF - Molecular biology of the cell AU - Torgan, C E AU - Daniels, M P AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-4036, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1499 EP - 1508 VL - 12 IS - 5 SN - 1059-1524, 1059-1524 KW - DNA-Binding Proteins KW - 0 KW - Enzyme Inhibitors KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Protein Isoforms KW - Transcription Factors KW - Tetrodotoxin KW - 4368-28-9 KW - Cyclosporine KW - 83HN0GTJ6D KW - Calcineurin KW - EC 3.1.3.16 KW - Myosin Heavy Chains KW - EC 3.6.4.1 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Transcription Factors -- metabolism KW - Protein Isoforms -- metabolism KW - Microscopy, Fluorescence KW - Rats KW - Signal Transduction -- physiology KW - Transfection KW - Cells, Cultured KW - Cyclosporine -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Protein Isoforms -- genetics KW - DNA-Binding Proteins -- metabolism KW - Calcineurin -- metabolism KW - Myosin Heavy Chains -- genetics KW - Muscle, Skeletal -- cytology KW - Muscle Fibers, Skeletal -- physiology KW - Muscle Development KW - Calcineurin -- genetics KW - Muscle, Skeletal -- growth & development KW - Myosin Heavy Chains -- metabolism KW - Muscle Contraction -- physiology KW - Muscle, Skeletal -- metabolism KW - Muscle Fibers, Skeletal -- drug effects KW - Muscle Fibers, Skeletal -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70887478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Regulation+of+myosin+heavy+chain+expression+during+rat+skeletal+muscle+development+in+vitro.&rft.au=Torgan%2C+C+E%3BDaniels%2C+M+P&rft.aulast=Torgan&rft.aufirst=C&rft.date=2001-05-01&rft.volume=12&rft.issue=5&rft.spage=1499&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=10591524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Dev Biol. 1988 Sep;129(1):37-47 [3044880] Philos Trans R Soc Lond B Biol Sci. 1981 Jul 16;293(1065):257-77 [6116248] J Neurol Sci. 1989 Jun;91(1-2):71-8 [2746293] Mol Cell Endocrinol. 1989 May;63(1-2):23-38 [2546840] Dev Biol. 1990 Apr;138(2):256-74 [2108065] Development. 1989 Dec;107(4):751-69 [2534377] J Neurocytol. 1992 May;21(5):329-40 [1607877] Nature. 1992 Jun 25;357(6380):692-4 [1377361] J Cell Biol. 1993 May;121(4):795-810 [8491773] Dev Biol. 1993 Jul;158(1):183-99 [7687223] Dev Biol. 1984 Apr;102(2):324-34 [6200371] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3733-7 [2424010] J Cell Biol. 1986 Dec;103(6 Pt 1):2153-61 [3782294] J Cell Biol. 1987 Mar;104(3):447-59 [3546335] Dev Genet. 1993;14(5):356-68 [8293577] Biochemistry. 1995 Apr 25;34(16):5561-8 [7727417] J Biol Chem. 1995 Nov 3;270(44):26511-22 [7592869] J Neurosci. 1995 Nov;15(11):7401-16 [7472493] Cell. 1995 Nov 3;83(3):463-72 [8521476] Nature. 1996 Oct 31;383(6603):837-40 [8893011] Nature. 1997 Apr 24;386(6627):855-8 [9126747] Annu Rev Immunol. 1997;15:707-47 [9143705] Dev Biol. 1997 Aug 1;188(1):167-80 [9245520] J Biol Chem. 1998 May 29;273(22):13367-70 [9593662] Genes Dev. 1998 Aug 15;12(16):2499-509 [9716403] Mol Biol Cell. 1998 Oct;9(10):2905-16 [9763451] Mol Cell Biol. 1998 Nov;18(11):6641-52 [9774679] Comp Biochem Physiol B Biochem Mol Biol. 1998 May;120(1):5-15 [9787775] Curr Biol. 1998 Dec 3;8(24):R892-4 [9843678] Mol Cell Biol. 1999 Jan;19(1):515-25 [9858575] J Cell Biol. 1999 May 3;145(3):633-42 [10225962] Muscle Nerve. 1999 Jun;22(6):666-77 [10366220] Nature. 1999 Aug 5;400(6744):581-5 [10448862] Science. 1999 Sep 24;285(5436):2129-33 [10497131] J Physiol. 1960 Feb;150:417-39 [13805874] J Biol Chem. 2000 Feb 18;275(7):4545-8 [10671477] J Physiol. 2000 Feb 15;523 Pt 1:19-28 [10673542] Nat Cell Biol. 2000 Mar;2(3):142-7 [10707084] Microsc Res Tech. 2000 Apr 1;49(1):26-37 [10757876] EMBO J. 2000 May 2;19(9):1963-73 [10790363] J Biol Chem. 2000 Jun 30;275(26):19653-60 [10777482] Mol Cell Biol. 2000 Sep;20(17):6600-11 [10938134] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Histochem Cytochem. 1973 Jan;21(1):51-5 [4348494] Nature. 1981 Aug 27;292(5826):805-9 [7196501] J Cell Biol. 1988 Dec;107(6 Pt 1):2191-7 [3058719] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell response endpoints enhance sensitivity of the immature mouse uterotropic assay. AN - 70881211; 11390168 AB - Outbred immature CD-1 mice were subcutaneously (s.c.) injected once on postnatal day 17 or on postnatal days 17, 18, and 19 with 17beta-estradiol, diethylstilbestrol, tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxychlor metabolite HPTE, nonylphenol, o,p'-DDT, endosulfan, or kepone over a wide dose range (0.1 to 1,000,000 microg/kg). On the day following the last injection, uterine weight/body weight ratios were determined and uterine tissues processed for histologic examination. All compounds except endosulfan and kepone increased uterine wet weight compared to vehicle controls; however, the dose response curve and magnitude of response varied depending on the compound. Choosing the maximum wet weight dose for each compound, uterine tissue was evaluated for epithelial cell height, epithelial and stromal cell proliferation, endometrial gland number, and induction of estrogen-inducible proteins lactoferrin and complement C3. All compounds elicited estrogen-responsive changes in these endpoints that were individually more sensitive than uterine weight alone. We conclude that these endpoints enhance the sensitivity of the uterotropic bioassay. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Newbold, R R AU - Jefferson, W N AU - Padilla-Banks, E AU - Walker, V R AU - Pena, D S AU - Developmental Endocrinology Studies Group AD - Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. newbold1@niehs.nih.gov ; Developmental Endocrinology Studies Group PY - 2001 SP - 245 EP - 252 VL - 15 IS - 3 SN - 0890-6238, 0890-6238 KW - Complement C3 KW - 0 KW - Environmental Pollutants KW - Estrogens KW - Estrogens, Non-Steroidal KW - Proliferating Cell Nuclear Antigen KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Animals, Outbred Strains KW - Dose-Response Relationship, Drug KW - Biological Assay KW - Cell Division -- drug effects KW - Complement C3 -- biosynthesis KW - Mice KW - Estrogens -- administration & dosage KW - Estrogens -- toxicity KW - Lactoferrin -- biosynthesis KW - Toxicity Tests KW - Injections, Subcutaneous KW - Image Processing, Computer-Assisted KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Female KW - Immunoenzyme Techniques KW - Organ Size -- drug effects KW - Uterus -- metabolism KW - Uterus -- growth & development KW - Environmental Pollutants -- toxicity KW - Estrogens, Non-Steroidal -- toxicity KW - Estrogens, Non-Steroidal -- administration & dosage KW - Uterus -- pathology KW - Environmental Pollutants -- administration & dosage KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70881211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Cell+response+endpoints+enhance+sensitivity+of+the+immature+mouse+uterotropic+assay.&rft.au=Newbold%2C+R+R%3BJefferson%2C+W+N%3BPadilla-Banks%2C+E%3BWalker%2C+V+R%3BPena%2C+D+S%3BDevelopmental+Endocrinology+Studies+Group&rft.aulast=Newbold&rft.aufirst=R&rft.date=2001-05-01&rft.volume=15&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-06-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Reprod Toxicol 2001 Jul-Aug;15(4):465-6 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypothalamic function in response to 2-deoxy-D-glucose in long-term abstinent alcoholics. AN - 70859735; 11371728 AB - The body adapts to diverse stressful stimuli with a response characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Chronic alcohol consumption can cause changes in the function of this neuroendocrine system. Although many studies have examined this phenomenon in drinking and recently sober alcoholics, few studies have examined HPA axis function in long-term sober alcoholics. To characterize HPA axis function in long-term sober alcoholics, we used a challenge paradigm with 2-deoxy-d-glucose (2-DG). An infusion of 2-DG (a nonmetabolizable glucose analog) induces a well-characterized stress response. In a previous study, our laboratory found an exaggerated corticotropin and cortisol response in alcoholics abstinent 3 weeks; in this investigation we compared the effects of an infusion of 2-DG on 19 healthy volunteers and 20 community-living alcoholics who had been abstinent more than 6 months. In contrast to the previous study, long-term sober alcoholics did not have an exaggerated corticotropin and cortisol response after 2-DG. Previously observed abnormalities in cortisol regulation in 3-week-sober alcoholics may be related to the acute effects of recent alcohol consumption and withdrawal. Future investigations into the metabolic function of alcoholics, particularly investigations involving the HPA system, should consider the possibility that normalization may not occur until long-term abstinence has been achieved. JF - Alcoholism, clinical and experimental research AU - Umhau, J C AU - Petrulis, S G AU - Diaz, R AU - Biddison, J R AU - George , A D AD - National Institute on Alcohol Abuse and Alcoholism Bethesda, Maryland 20892-1610, USA. Umhau@nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 781 EP - 786 VL - 25 IS - 5 SN - 0145-6008, 0145-6008 KW - Antimetabolites KW - 0 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Deoxyglucose KW - 9G2MP84A8W KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- drug effects KW - Analysis of Variance KW - Humans KW - Adult KW - Hypothalamo-Hypophyseal System -- metabolism KW - Middle Aged KW - Antimetabolites -- pharmacology KW - Adrenocorticotropic Hormone -- drug effects KW - Temperance KW - Deoxyglucose -- pharmacology KW - Hydrocortisone -- blood KW - Alcoholism -- blood KW - Adrenocorticotropic Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70859735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Hypothalamic+function+in+response+to+2-deoxy-D-glucose+in+long-term+abstinent+alcoholics.&rft.au=Umhau%2C+J+C%3BPetrulis%2C+S+G%3BDiaz%2C+R%3BBiddison%2C+J+R%3BGeorge+%2C+A+D&rft.aulast=Umhau&rft.aufirst=J&rft.date=2001-05-01&rft.volume=25&rft.issue=5&rft.spage=781&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Post-episode depression of GABAergic transmission in spinal neurons of the chick embryo. AN - 70854523; 11353031 AB - Whole cell recordings were obtained from ventral horn neurons in spontaneously active spinal cords isolated from the chick embryo [embryonic days 10 to 11 (E10-E11)] to examine the post-episode depression of GABAergic transmission. Spontaneous activity occurred as recurrent, rhythmic episodes approximately 60 s in duration with 10- to 15-min quiescent inter-episode intervals. Current-clamp recording revealed that episodes were followed by a transient hyperpolarization (7 +/- 1.2 mV, mean +/- SE), which dissipated as a slow (0.5-1 mV/min) depolarization until the next episode. Local application of bicuculline 8 min after an episode hyperpolarized spinal neurons by 6 +/- 0.8 mV and increased their input resistance by 13%, suggesting the involvement of GABAergic transmission. Gramicidin perforated-patch recordings showed that the GABAa reversal potential was above rest potential (E(GABAa) = -29 +/- 3 mV) and allowed estimation of the physiological intracellular [Cl(-)] = 50 mM. In whole cell configuration (with physiological electrode [Cl(-)]), two distinct types of endogenous GABAergic currents (I(GABAa)) were found during the inter-episode interval. The first comprised TTX-resistant, asynchronous miniature postsynaptic currents (mPSCs), an indicator of quantal GABA release (up to 42% of total mPSCs). The second (tonic I(GABAa)) was complimentary to the slow membrane depolarization and may arise from persistent activation of extrasynaptic GABAa receptors. We estimate that approximately 10 postsynaptic channels are activated by a single quantum of GABA release during an mPSC and that about 30 extrasynaptic GABAa channels are required for generation of the tonic I(GABAa) in ventral horn neurons. We investigated the post-episode depression of I(GABAa) by local application of GABA or isoguvacine (100 microM, for 10-30 s) applied before and after an episode at holding potentials (V(hold)) -60 mV. The amplitude of the evoked I(GABA) was compared after clamping the cell during the episode at one of three different V(hold): -60 mV, below E(GABAa) resulting in Cl(-) efflux; -30 mV, close to E(GABAa) with minimal Cl(-) flux; and 0 mV, above E(GABAa) resulting in Cl(-) influx during the episode. The amplitude of the evoked I(GABA) changed according to the direction of Cl(-) flux during the episode: at -60 mV a 41% decrease, at -30 mV a 4% reduction, and at 0 mV a 19% increase. These post-episode changes were accompanied by shifts of E(GABAa) of -10, -1.2, and +7 mV, respectively. We conclude that redistribution of intracellular [Cl(-)] during spontaneous episodes is likely to be an important postsynaptic mechanism involved in the post-episode depression of GABAergic transmission in chick embryo spinal neurons. JF - Journal of neurophysiology AU - Chub, N AU - O'Donovan, M J AD - Section on Developmental Neurobiology, Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. chubn@ninds.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 2166 EP - 2176 VL - 85 IS - 5 SN - 0022-3077, 0022-3077 KW - Chloride Channels KW - 0 KW - Chlorides KW - Excitatory Amino Acid Antagonists KW - GABA Agonists KW - GABA Antagonists KW - Isonicotinic Acids KW - Nerve Tissue Proteins KW - Receptors, GABA-A KW - Gramicidin KW - 1405-97-6 KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Bicuculline KW - Y37615DVKC KW - isoguvacine KW - YTF580771Y KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Ion Transport -- drug effects KW - Chick Embryo KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Chloride Channels -- metabolism KW - Action Potentials -- drug effects KW - Chlorides -- metabolism KW - GABA Antagonists -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Evoked Potentials -- drug effects KW - Patch-Clamp Techniques KW - GABA Agonists -- pharmacology KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Chloride Channels -- drug effects KW - Periodicity KW - Membrane Potentials -- drug effects KW - Gramicidin -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Isonicotinic Acids -- pharmacology KW - Nerve Tissue Proteins -- physiology KW - Nerve Tissue Proteins -- drug effects KW - Refractory Period, Electrophysiological -- physiology KW - Receptors, GABA-A -- physiology KW - Refractory Period, Electrophysiological -- drug effects KW - Synaptic Transmission -- drug effects KW - Anterior Horn Cells -- physiology KW - gamma-Aminobutyric Acid -- secretion KW - Receptors, GABA-A -- drug effects KW - Synaptic Transmission -- physiology KW - Spinal Cord -- embryology KW - Anterior Horn Cells -- drug effects KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70854523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Post-episode+depression+of+GABAergic+transmission+in+spinal+neurons+of+the+chick+embryo.&rft.au=Chub%2C+N%3BO%27Donovan%2C+M+J&rft.aulast=Chub&rft.aufirst=N&rft.date=2001-05-01&rft.volume=85&rft.issue=5&rft.spage=2166&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-30 N1 - Date created - 2001-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary intake of heterocyclic amines, meat-derived mutagenic activity, and risk of colorectal adenomas. AN - 70854166; 11352869 AB - Meats cooked well-done by high temperature techniques produce mutagenic compounds such as heterocyclic amines (HCAs), but the amounts of these compounds vary by cooking techniques, temperature, time, and type of meat. We investigated the role of HCAs in the etiology of colorectal adenomas and the extent to which they may explain the previously observed risk for red meat and meat-cooking methods. In a case-control study of colorectal adenomas, cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy, and controls (n = 228) were found not to have colorectal adenomas at sigmoidoscopy. Using a meat-derived HCA and mutagen database and responses from a meat-cooking questionnaire module, we estimated intake of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and mutagenic activity. We calculated odds ratios and 95% confidence intervals using logistic regression adjusting for several established risk factors for colorectal adenomas or cancer. The odds ratios (95% confidence interval; P for trend test) fifth versus first quintiles are: 2.2 (1.2-4.1; P = 0.02) for DiMeIQx; 2.1 (1.0-4.3; P = 0.002) for MeIQx; 2.5(1.1-5.5; P = 0.02) for PhIP; and 3.1 (1.4-6.8; P = 0.001) for mutagenic activity. When the three HCAs were adjusted for the other two, only the trend for MeIQx (P = 0.04) remained statistically significant. When we tried to disentangle the relative contribution of the three HCAs from the meat variables, we found that MeIQx remained significantly associated with risk even when adjusted for red meat but not vice versa. When MeIQx and well-done meat were analyzed in the same model, the risks were attenuated for both. Mutagenic activity from meat remained significantly associated with increased risk even when adjusted for intake of red meat or well-done red meat, whereas the red meat and well-done red meat associations were no longer significant when adjusted for total mutagenic activity. In conclusion, we found an elevated risk of colorectal adenomas associated with high intake of certain HCAS: Further, mutagenic activity from cooked meat consumption, a measure that integrates all of the classes of mutagens, was strongly associated with risk and explained the excess risk with intake of well-done red meat. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Sinha, R AU - Kulldorff, M AU - Chow, W H AU - Denobile, J AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland 20892, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 559 EP - 562 VL - 10 IS - 5 SN - 1055-9965, 1055-9965 KW - Amines KW - 0 KW - Heterocyclic Compounds KW - Mutagens KW - Index Medicus KW - Reference Values KW - Odds Ratio KW - Humans KW - Food Handling -- methods KW - Aged KW - Risk Assessment KW - Diet -- adverse effects KW - Hot Temperature KW - Mutagenicity Tests KW - Logistic Models KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - Female KW - Male KW - Meat -- adverse effects KW - Mutagens -- adverse effects KW - Adenoma -- epidemiology KW - Colorectal Neoplasms -- etiology KW - Adenoma -- etiology KW - Heterocyclic Compounds -- adverse effects KW - Colorectal Neoplasms -- epidemiology KW - Mutagens -- chemistry KW - Amines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70854166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Dietary+intake+of+heterocyclic+amines%2C+meat-derived+mutagenic+activity%2C+and+risk+of+colorectal+adenomas.&rft.au=Sinha%2C+R%3BKulldorff%2C+M%3BChow%2C+W+H%3BDenobile%2C+J%3BRothman%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=2001-05-01&rft.volume=10&rft.issue=5&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical characterization of human DNA polymerase iota provides clues to its biological function. AN - 70854063; 11356150 AB - The human RAD30B gene has recently been shown to encode a novel DNA polymerase, DNA polymerase iota (poliota). The role of poliota within the cell is presently unknown, and the only clues to its cellular function come from its biochemical characterization in vitro. The aim of this short review is, therefore, to summarize the known enzymic activities of poliota and to speculate as to how these biochemical properties might relate to its in vivo function. JF - Biochemical Society transactions AU - Tissier, A AU - Frank, E G AU - McDonald, J P AU - Vaisman, A AU - Fernàndez de Henestrosa, A R AU - Boudsocq, F AU - McLenigan, M P AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, U.S.A. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 183 EP - 187 VL - 29 SN - 0300-5127, 0300-5127 KW - DNA Polymerase I KW - EC 2.7.7.- KW - DNA polymerase iota KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - DNA Repair -- genetics KW - Base Sequence KW - Humans KW - Base Pair Mismatch -- genetics KW - DNA Damage -- genetics KW - DNA Replication KW - DNA Polymerase I -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70854063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Society+transactions&rft.atitle=Biochemical+characterization+of+human+DNA+polymerase+iota+provides+clues+to+its+biological+function.&rft.au=Tissier%2C+A%3BFrank%2C+E+G%3BMcDonald%2C+J+P%3BVaisman%2C+A%3BFern%C3%A0ndez+de+Henestrosa%2C+A+R%3BBoudsocq%2C+F%3BMcLenigan%2C+M+P%3BWoodgate%2C+R&rft.aulast=Tissier&rft.aufirst=A&rft.date=2001-05-01&rft.volume=29&rft.issue=&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+transactions&rft.issn=03005127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factors and prostate cancer: a population-based case-control study in China. AN - 70850532; 11352850 AB - Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19-5.79; P(trend) = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26-1.15; P(trend) = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31-1.17; P(trend) = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32-4.75, P(trend) < 0.001). These associations were more pronounced after adjustment for serum 5alpha-androstane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Chokkalingam, A P AU - Pollak, M AU - Fillmore, C M AU - Gao, Y T AU - Stanczyk, F Z AU - Deng, J AU - Sesterhenn, I A AU - Mostofi, F K AU - Fears, T R AU - Madigan, M P AU - Ziegler, R G AU - Fraumeni, J F AU - Hsing, A W AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 421 EP - 427 VL - 10 IS - 5 SN - 1055-9965, 1055-9965 KW - Biomarkers, Tumor KW - 0 KW - Insulin-Like Growth Factor Binding Protein 1 KW - Insulin-Like Growth Factor Binding Protein 3 KW - Somatomedins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - Sensitivity and Specificity KW - Probability KW - Insulin-Like Growth Factor II -- analysis KW - Reference Values KW - Odds Ratio KW - Humans KW - Aged KW - Insulin-Like Growth Factor I -- analysis KW - Population Surveillance KW - Multivariate Analysis KW - China -- epidemiology KW - Case-Control Studies KW - Confidence Intervals KW - Enzyme-Linked Immunosorbent Assay KW - Middle Aged KW - Male KW - Somatomedins -- analysis KW - Prostatic Neoplasms -- epidemiology KW - Prostatic Neoplasms -- diagnosis KW - Insulin-Like Growth Factor Binding Protein 1 -- analysis KW - Prostatic Neoplasms -- blood KW - Biomarkers, Tumor -- blood KW - Insulin-Like Growth Factor Binding Protein 3 -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70850532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Insulin-like+growth+factors+and+prostate+cancer%3A+a+population-based+case-control+study+in+China.&rft.au=Chokkalingam%2C+A+P%3BPollak%2C+M%3BFillmore%2C+C+M%3BGao%2C+Y+T%3BStanczyk%2C+F+Z%3BDeng%2C+J%3BSesterhenn%2C+I+A%3BMostofi%2C+F+K%3BFears%2C+T+R%3BMadigan%2C+M+P%3BZiegler%2C+R+G%3BFraumeni%2C+J+F%3BHsing%2C+A+W&rft.aulast=Chokkalingam&rft.aufirst=A&rft.date=2001-05-01&rft.volume=10&rft.issue=5&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fludarabine pharmacokinetics after subcutaneous and intravenous administration in patients with lupus nephritis. AN - 70837348; 11349741 AB - To compare the pharmacokinetics of subcutaneous and intravenous fludarabine in patients with lupus nephritis. Open-label, randomized, crossover trial conducted with a phase I-II trial. Government research hospital. Five patients with lupus nephritis. Fludarabine 30 mg/m2/day was administered either subcutaneously or as a 0.5-hour intravenous infusion for 3 consecutive days. All patients received oral cyclophosphamide 0.5 g/m2 on the first day of each cycle. Plasma samples were collected before and 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the first dose. Urine was collected at 6-hour intervals for 24 hours. Plasma and urine were analyzed for fluoro-arabinofuranosyladenine (F-ara-A), fludarabine's main metabolite, using high-performance liquid chromatography. Compartmental techniques were used to determine the pharmacokinetics of F-ara-A; a linear two-compartment model best described them. Comparison of the pharmacokinetics between subcutaneous and intravenous administration was done by using a Wilcoxon signed rank test. No significant differences were found between subcutaneous and intravenous administration in median (interquartile range) maximum concentrations of 0.51 (0.38-0.56) and 0.75 (0.52-0.91) mg/L, respectively, or in fitted area under the concentration-time curves from 0-24 hours of 4.65 (4.17-4.98) and 4.55 (3.5-4.94) mg x hour/L, respectively. Bioavailability of F-ara-A after subcutaneous dosing was approximately 105% of the bioavailability after intravenous administration. Differences in renal clearance and percentage of dose excreted in urine for subcutaneous and intravenous administration were nonsignificant. No injection site reactions were seen with subcutaneous dosing. Subcutaneous and intravenous administration of fludarabine appear to have similar pharmacokinetics in patients with lupus nephritis. Subcutaneous injection may offer a convenient alternative to intravenous administration. JF - Pharmacotherapy AU - Kuo, G M AU - Boumpas, D T AU - Illei, G G AU - Yarboro, C AU - Pucino, F AU - Burstein, A H AD - Department of Pharmacy, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 528 EP - 533 VL - 21 IS - 5 SN - 0277-0008, 0277-0008 KW - Antineoplastic Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Infusions, Intravenous KW - Humans KW - Adult KW - Injections, Subcutaneous KW - Cross-Over Studies KW - Confidence Intervals KW - Middle Aged KW - Statistics, Nonparametric KW - Male KW - Female KW - Lupus Nephritis -- metabolism KW - Vidarabine -- analogs & derivatives KW - Lupus Nephritis -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Vidarabine -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Vidarabine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70837348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Fludarabine+pharmacokinetics+after+subcutaneous+and+intravenous+administration+in+patients+with+lupus+nephritis.&rft.au=Kuo%2C+G+M%3BBoumpas%2C+D+T%3BIllei%2C+G+G%3BYarboro%2C+C%3BPucino%2C+F%3BBurstein%2C+A+H&rft.aulast=Kuo&rft.aufirst=G&rft.date=2001-05-01&rft.volume=21&rft.issue=5&rft.spage=528&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. AN - 70835610; 11350913 AB - We have shown that activation of nuclear factor-kappa B (NF-kappa B) promotes cell survival and expression of cytokines such as growth-regulated oncogene-alpha, which can modulate angiogenesis, growth, and metastasis of squamous cell carcinoma (SCC). Activation of NF-kappa B and cytoprotective genes in cancer may result from signal-induced phosphorylation and proteasome-dependent degradation of inhibitor-kappa B. In this study, we examined the effects of the novel proteasome inhibitor PS-341 on activation of NF-kappa B and cell survival, growth, and angiogenesis in murine and human SCC cell lines. PS-341 inhibited activation of NF-kappa B DNA binding and functional reporter activity at concentrations between 10(-8) and 10(-7) M. Cytotoxicity was observed at 10(-7) M in four murine and two human SCC lines, and followed early cleavage of poly(ADP-ribose) polymerase, a marker of caspase-mediated apoptosis. In vivo, PS-341 inhibited growth of murine and human SCC in mice at doses of 1--2 mg/kg given three times weekly, and dose-limiting toxicity was encountered at 2 mg/kg. Tumor growth inhibition was associated with a marked decrease in vessel density. PS-341 inhibited expression of the proangiogenic cytokines growth-regulated oncogene-alpha and vascular endothelial growth factor by SCC in the range at which PS-341 inhibits NF-kappa B. We conclude that PS-341 inhibits activation of NF-kappa B pathway components related to cell survival, tumor growth, and angiogenesis in SCC. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Sunwoo, J B AU - Chen, Z AU - Dong, G AU - Yeh, N AU - Crowl Bancroft, C AU - Sausville, E AU - Adams, J AU - Elliott, P AU - Van Waes, C AD - Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1419 EP - 1428 VL - 7 IS - 5 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Boronic Acids KW - Cytokines KW - Multienzyme Complexes KW - NF-kappa B KW - Pyrazines KW - Bortezomib KW - 69G8BD63PP KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Cytokines -- biosynthesis KW - Humans KW - Neovascularization, Pathologic -- metabolism KW - Blood Vessels -- drug effects KW - Cell Division -- drug effects KW - Disease Models, Animal KW - Mice KW - Mice, Inbred BALB C KW - Neoplasm Transplantation KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Treatment Outcome KW - Xenograft Model Antitumor Assays KW - Neoplasms, Experimental -- drug therapy KW - Mice, SCID KW - Carcinoma, Squamous Cell KW - Boronic Acids -- pharmacology KW - Pyrazines -- therapeutic use KW - Pyrazines -- pharmacology KW - Multienzyme Complexes -- antagonists & inhibitors KW - Antineoplastic Agents -- therapeutic use KW - Boronic Acids -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70835610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Novel+proteasome+inhibitor+PS-341+inhibits+activation+of+nuclear+factor-kappa+B%2C+cell+survival%2C+tumor+growth%2C+and+angiogenesis+in+squamous+cell+carcinoma.&rft.au=Sunwoo%2C+J+B%3BChen%2C+Z%3BDong%2C+G%3BYeh%2C+N%3BCrowl+Bancroft%2C+C%3BSausville%2C+E%3BAdams%2C+J%3BElliott%2C+P%3BVan+Waes%2C+C&rft.aulast=Sunwoo&rft.aufirst=J&rft.date=2001-05-01&rft.volume=7&rft.issue=5&rft.spage=1419&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 2015 Mar 1;21(5):942-3 [25733706] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. AN - 70834798; 11344116 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Fletcher, C F AU - Tottene, A AU - Lennon, V A AU - Wilson, S M AU - Dubel, S J AU - Paylor, R AU - Hosford, D A AU - Tessarollo, L AU - McEnery, M W AU - Pietrobon, D AU - Copeland, N G AU - Jenkins, N A AD - Mouse Cancer Genetics Program, National Cancer Institute-FCRDC, Frederick, Maryland 21702, USA. Fletcher@gnf.org Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1288 EP - 1290 VL - 15 IS - 7 SN - 0892-6638, 0892-6638 KW - CACNA1A protein, human KW - 0 KW - Calcium Channel Blockers KW - Calcium Channels KW - Calcium Channels, N-Type KW - Calcium Channels, P-Type KW - Calcium Channels, Q-Type KW - omega-Conotoxins KW - voltage-dependent calcium channel (P-Q type) KW - omega-conotoxin-MVIIC KW - 147794-23-8 KW - Nimodipine KW - 57WA9QZ5WH KW - omega-Conotoxin GVIA KW - 92078-76-7 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Transgenic KW - Patch-Clamp Techniques KW - Calcium Channel Blockers -- pharmacology KW - Cells, Cultured KW - Nimodipine -- pharmacology KW - omega-Conotoxins -- pharmacology KW - omega-Conotoxin GVIA -- pharmacology KW - Cerebellum -- cytology KW - Calcium Channels -- metabolism KW - Cerebellum -- drug effects KW - Cerebellar Ataxia -- physiopathology KW - Cerebellum -- pathology KW - Calcium Channels -- genetics KW - Gene Targeting KW - Cerebellum -- physiopathology KW - Cerebellar Ataxia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70834798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Dystonia+and+cerebellar+atrophy+in+Cacna1a+null+mice+lacking+P%2FQ+calcium+channel+activity.&rft.au=Fletcher%2C+C+F%3BTottene%2C+A%3BLennon%2C+V+A%3BWilson%2C+S+M%3BDubel%2C+S+J%3BPaylor%2C+R%3BHosford%2C+D+A%3BTessarollo%2C+L%3BMcEnery%2C+M+W%3BPietrobon%2C+D%3BCopeland%2C+N+G%3BJenkins%2C+N+A&rft.aulast=Fletcher&rft.aufirst=C&rft.date=2001-05-01&rft.volume=15&rft.issue=7&rft.spage=1288&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. AN - 70832134; 11343253 AB - The UDP-glucuronosyltransferase, UGT1A1, is the critical enzyme responsible for detoxification of the potentially neurotoxic bilirubin by conjugating it with glucuronic acid. For decades, phenobarbital (PB) treatment for hyperbilirubinemia has been known to increase expression of the UGT1A1 gene in liver. We have now delineated the PB response activity to a 290-bp distal enhancer sequence (-3483/-3194) of the UGT1A1 gene. The enhancer contains 3 putative nuclear receptor motifs, and it was activated by the nuclear orphan receptor, human constitutive active receptor (hCAR), in cotransfected HepG2 cells. Bacterially expressed hCAR, acting as a heterodimer with in vitro-translated retinoid X receptor (RXRalpha), only bound to 1 of the 3 NR motifs, named gtNR1 in a gel-shift assay. Consistently, mutations of the gtNR1 site significantly decreased the activation by hCAR of the 290-bp DNA in transfection assays. Moreover, the 290-bp DNA was effectively activated in mouse primary hepatocytes in response to PB, offering an excellent clinical test for the examination of the responsiveness of the UGT1A1 to PB in the human population, particularly individuals with hyperbilirubinemia. JF - Hepatology (Baltimore, Md.) AU - Sugatani, J AU - Kojima, H AU - Ueda, A AU - Kakizaki, S AU - Yoshinari, K AU - Gong, Q H AU - Owens, I S AU - Negishi, M AU - Sueyoshi, T AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1232 EP - 1238 VL - 33 IS - 5 SN - 0270-9139, 0270-9139 KW - Receptors, Cytoplasmic and Nuclear KW - 0 KW - Transcription Factors KW - constitutive androstane receptor KW - DNA KW - 9007-49-2 KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Base Sequence -- genetics KW - Transfection KW - Cells, Cultured KW - Humans KW - DNA -- genetics KW - Molecular Sequence Data KW - DNA -- physiology KW - Mutation KW - Gene Deletion KW - DNA -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Phenobarbital -- pharmacology KW - Glucuronosyltransferase -- genetics KW - Gene Expression Regulation -- physiology KW - Enhancer Elements, Genetic -- physiology KW - Glucuronosyltransferase -- drug effects KW - Response Elements -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70832134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=The+phenobarbital+response+enhancer+module+in+the+human+bilirubin+UDP-glucuronosyltransferase+UGT1A1+gene+and+regulation+by+the+nuclear+receptor+CAR.&rft.au=Sugatani%2C+J%3BKojima%2C+H%3BUeda%2C+A%3BKakizaki%2C+S%3BYoshinari%2C+K%3BGong%2C+Q+H%3BOwens%2C+I+S%3BNegishi%2C+M%3BSueyoshi%2C+T&rft.aulast=Sugatani&rft.aufirst=J&rft.date=2001-05-01&rft.volume=33&rft.issue=5&rft.spage=1232&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial DNA in human malignancy. AN - 70825038; 11344040 AB - Alterations in expression of mitochondrial DNA (mtDNA)-encoded polypeptides required for oxidative phosphorylation and cellular ATP generation may be a general characteristic of cancer cells. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Since mtDNA lacks introns, it has been suggested that most mutations will occur in coding sequences and subsequent accumulation of mutations may lead to tumor formation. The mitochondrial genome is dependent upon the nuclear genome for transcription, translation, replication and repair, but precise mechanisms for how the two genomes interact and integrate with each other are poorly understood. In solid tumors, elevated expression of mtDNA-encoded subunits of the mitochondrial electron respiratory chain may reflect mitochondrial adaptation to perturbations in cellular energy requirements. In this paper, we review mitochondrial genomic aberrations reported in solid tumors of the breast, colon, stomach, liver, kidney, bladder, head/neck and lung as well as for hematologic diseases such as leukemia, myelodysplastic syndrome and lymphoma. We include data for elevated expression of mtDNA-encoded electron respiratory chain subunits in breast, colon and liver cancers and also the mutations reported in cancers of the colon, stomach, bladder, head/neck and lung. Finally, we examine the role of reactive oxygen species (ROS) generated by mitochondria in the process of carcinogenesis. JF - Mutation research AU - Penta, J S AU - Johnson, F M AU - Wachsman, J T AU - Copeland, W C AD - Office of Clinical Research, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD A2-05, Research Triangle Park, NC 27709, USA. penta@niehs.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 119 EP - 133 VL - 488 IS - 2 SN - 0027-5107, 0027-5107 KW - DNA, Mitochondrial KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Kidney Neoplasms -- genetics KW - Reactive Oxygen Species -- metabolism KW - Humans KW - Colorectal Neoplasms -- genetics KW - Leukemia -- genetics KW - Lymphoma -- genetics KW - Stomach Neoplasms -- genetics KW - Hematologic Neoplasms -- genetics KW - Electron Transport -- genetics KW - Female KW - Male KW - Liver Neoplasms -- genetics KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- metabolism KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70825038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mitochondrial+DNA+in+human+malignancy.&rft.au=Penta%2C+J+S%3BJohnson%2C+F+M%3BWachsman%2C+J+T%3BCopeland%2C+W+C&rft.aulast=Penta&rft.aufirst=J&rft.date=2001-05-01&rft.volume=488&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thyroid cancer after radiotherapy for childhood cancer. AN - 70823732; 11340614 AB - The thyroid gland in children is among the most sensitive organs to the carcinogenic effects of ionizing radiation, and very young children are at especially high risk. Risk associated with exposure to external X- or gamma-radiation increases linearly with increasing dose to the thyroid gland at low-to-moderate doses, but the dose-response relationship appears to flatten at the very high doses characteristic of cancer radiotherapy. Because of the extreme sensitivity of the thyroid gland in children, there is a risk of radiation-induced thyroid cancer even when the thyroid gland is outside of the irradiated field. Increased incidence of thyroid cancer has been noted following radiotherapy for childhood Hodgkin disease, non-Hodgkin lymphoma, neuroblastoma, Wilms tumor, acute lymphocytic leukemia and tumors of the central nervous system. Radiation-induced tumors begin to appear 5-10 years after irradiation and excess risk persists for decades, perhaps for the remainder of life. The background incidence of thyroid cancer is two- to threefold higher among females than males, and the absolute increase in risk due to irradiation is higher in females as well. Most of the thyroid cancers that occur in association with irradiation are of the papillary type, for which the cure rate is high if tumors are detected early. This highlights the importance of long-term surveillance of persons irradiated during childhood. Important areas for research include the possibility that children with certain types of first cancer are especially susceptible, the basis of the greater female susceptibility, the joint effects of radiation and other factors, and genetic mechanisms in radiation-induced and spontaneously occurring thyroid cancer. Copyright 2001 Wiley-Liss, Inc. JF - Medical and pediatric oncology AU - Inskip, P D AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. inskippe@mail.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 568 EP - 573 VL - 36 IS - 5 SN - 0098-1532, 0098-1532 KW - Index Medicus KW - Sex Factors KW - Neoplasms -- radiotherapy KW - Humans KW - Incidence KW - Child KW - Survivors KW - Male KW - Female KW - Thyroid Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70823732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology&rft.atitle=Thyroid+cancer+after+radiotherapy+for+childhood+cancer.&rft.au=Inskip%2C+P+D&rft.aulast=Inskip&rft.aufirst=P&rft.date=2001-05-01&rft.volume=36&rft.issue=5&rft.spage=568&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology&rft.issn=00981532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of loss of heterozygosity at chromosome 3p25-26 in primary and metastatic ovarian clear-cell carcinoma: utilization of microdissection and polymerase chain reaction in archival tissues. AN - 70820624; 11335962 AB - Loss of heterozygosity (LOH) at the 3p region is found in up to 50% of epithelial ovarian neoplasms. The von Hippel-Lindau (VHL) gene at the 3p25 locus is one of the tumor-suppressor genes located at 3p. The role, if any, of the VHL gene locus is not clear in ovarian carcinogenesis. We analyzed primary and metastatic ovarian clear-cell carcinomas (OCCC) for LOH at 3p25 to determine its frequency and its diagnostic utility as an adjunctive tool in the differential diagnosis of metastatic clear-cell carcinomas. Microdissection followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification, using two polymorphic markers flanking the VHL gene locus, was done on archival histology and cytology samples from 9 patients with metastatic OCCC. Of the informative cases, 43% of the metastatic and 50% of the primary OCCC showed LOH. LOH at the VHL gene locus is not uncommon in clear-cell ovarian carcinoma. LOH at 3p25 in cytologic specimens may be a valuable adjunct in the diagnosis of OCCC metastasis in cytologically equivocal cases. OCCC should enter the differential in clear-cell carcinomas of unknown primary that show LOH at 3p25. Published 2001 Wiley-Liss, Inc. JF - Diagnostic cytopathology AU - Simsir, A AU - Palacios, D AU - Linehan, W M AU - Merino, M J AU - Abati, A AD - Cytopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 328 EP - 332 VL - 24 IS - 5 SN - 8755-1039, 8755-1039 KW - Biomarkers, Tumor KW - 0 KW - Proteins KW - Tumor Suppressor Proteins KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - Diagnosis, Differential KW - Genes, Tumor Suppressor -- genetics KW - Humans KW - Retrospective Studies KW - Proteins -- genetics KW - Female KW - Adenocarcinoma, Clear Cell -- genetics KW - Ovarian Neoplasms -- secondary KW - Ovarian Neoplasms -- genetics KW - Chromosomes, Human, Pair 3 -- genetics KW - Polymerase Chain Reaction KW - Adenocarcinoma, Clear Cell -- secondary KW - Ovarian Neoplasms -- pathology KW - Loss of Heterozygosity -- genetics KW - Adenocarcinoma, Clear Cell -- pathology KW - Dissection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70820624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diagnostic+cytopathology&rft.atitle=Detection+of+loss+of+heterozygosity+at+chromosome+3p25-26+in+primary+and+metastatic+ovarian+clear-cell+carcinoma%3A+utilization+of+microdissection+and+polymerase+chain+reaction+in+archival+tissues.&rft.au=Simsir%2C+A%3BPalacios%2C+D%3BLinehan%2C+W+M%3BMerino%2C+M+J%3BAbati%2C+A&rft.aulast=Simsir&rft.aufirst=A&rft.date=2001-05-01&rft.volume=24&rft.issue=5&rft.spage=328&rft.isbn=&rft.btitle=&rft.title=Diagnostic+cytopathology&rft.issn=87551039&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection. AN - 70819479; 11335705 AB - Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis. JF - Brain : a journal of neurology AU - Heyes, M P AU - Ellis, R J AU - Ryan, L AU - Childers, M E AU - Grant, I AU - Wolfson, T AU - Archibald, S AU - Jernigan, T L AU - HNRC Group. HIV Neurobehavioral Research Center AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland, USA. ; HNRC Group. HIV Neurobehavioral Research Center Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1033 EP - 1042 VL - 124 SN - 0006-8950, 0006-8950 KW - Biomarkers KW - 0 KW - RNA, Viral KW - beta 2-Microglobulin KW - Quinolinic Acid KW - F6F0HK1URN KW - Abridged Index Medicus KW - Index Medicus KW - Virus Replication KW - Magnetic Resonance Imaging KW - HIV-1 -- isolation & purification KW - Humans KW - Predictive Value of Tests KW - HIV Seropositivity -- complications KW - Biomarkers -- cerebrospinal fluid KW - Cross-Sectional Studies KW - beta 2-Microglobulin -- blood KW - beta 2-Microglobulin -- cerebrospinal fluid KW - HIV Seropositivity -- diagnosis KW - Adult KW - Cohort Studies KW - RNA, Viral -- cerebrospinal fluid KW - Limbic System -- pathology KW - Middle Aged KW - Corpus Striatum -- pathology KW - Male KW - Atrophy -- diagnosis KW - Quinolinic Acid -- cerebrospinal fluid KW - HIV Infections -- virology KW - HIV Infections -- complications KW - Quinolinic Acid -- blood KW - Brain -- pathology KW - Atrophy -- etiology KW - HIV Infections -- cerebrospinal fluid KW - Atrophy -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70819479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+%3A+a+journal+of+neurology&rft.atitle=Elevated+cerebrospinal+fluid+quinolinic+acid+levels+are+associated+with+region-specific+cerebral+volume+loss+in+HIV+infection.&rft.au=Heyes%2C+M+P%3BEllis%2C+R+J%3BRyan%2C+L%3BChilders%2C+M+E%3BGrant%2C+I%3BWolfson%2C+T%3BArchibald%2C+S%3BJernigan%2C+T+L%3BHNRC+Group.+HIV+Neurobehavioral+Research+Center&rft.aulast=Heyes&rft.aufirst=M&rft.date=2001-05-01&rft.volume=124&rft.issue=&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Brain+%3A+a+journal+of+neurology&rft.issn=00068950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Saccharomyces cerevisiae SMT4 encodes an evolutionarily conserved protease with a role in chromosome condensation regulation. AN - 70817486; 11333221 AB - In a search for regulatory genes affecting the targeting of the condensin complex to chromatin in Saccharomyces cerevisiae, we identified a member of the adenovirus protease family, SMT4. SMT4 overexpression suppresses the temperature-sensitive conditional lethal phenotype of smc2-6, but not smc2-8 or smc4-1. A disruption allele of SMT4 has a prominent chromosome phenotype: impaired targeting of Smc4p-GFP to rDNA chromatin. Site-specific mutagenesis of the predicted protease active site cysteine and histidine residues of Smt4p abolishes the SMT4 function in vivo. The previously uncharacterized SIZ1 (SAP and Miz) gene, which encodes a protein containing a predicted DNA-binding SAP module and a Miz finger, is identified as a bypass suppressor of the growth defect associated with the SMT4 disruption. The SIZ1 gene disruption is synthetically lethal with the SIZ2 deletion. We propose that SMT4, SIZ1, and SIZ2 are involved in a novel pathway of chromosome maintenance. JF - Genetics AU - Strunnikov, A V AU - Aravind, L AU - Koonin, E V AD - National Institute of Child Health and Human Development, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892, USA. strunnik@box-s.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 95 EP - 107 VL - 158 IS - 1 SN - 0016-6731, 0016-6731 KW - DNA, Ribosomal KW - 0 KW - Saccharomyces cerevisiae Proteins KW - Endopeptidases KW - EC 3.4.- KW - ULP2 protein, S cerevisiae KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Conserved Sequence KW - Mitosis -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Genes, Lethal KW - DNA, Ribosomal -- genetics KW - Gene Deletion KW - Saccharomyces cerevisiae -- genetics KW - Endopeptidases -- genetics KW - Endopeptidases -- chemistry KW - Evolution, Molecular KW - Chromosomes, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70817486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Saccharomyces+cerevisiae+SMT4+encodes+an+evolutionarily+conserved+protease+with+a+role+in+chromosome+condensation+regulation.&rft.au=Strunnikov%2C+A+V%3BAravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Strunnikov&rft.aufirst=A&rft.date=2001-05-01&rft.volume=158&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-05-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Cell Biol. 1999;77(4):299-309 [10546893] Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 [9396791] Philos Trans R Soc Lond B Biol Sci. 1999 Sep 29;354(1389):1533-50 [10582239] Philos Trans R Soc Lond B Biol Sci. 1999 Sep 29;354(1389):1583-90 [10582244] Nature. 1999 Dec 2;402(6761):555-60 [10591219] Nucleic Acids Res. 2000 Jan 1;28(1):323-5 [10592261] J Cell Biol. 1999 Dec 13;147(6):1167-80 [10601332] Biochem Biophys Res Commun. 1999 Dec 29;266(3):633-40 [10603300] Trends Biochem Sci. 2000 Mar;25(3):112-4 [10694879] Mol Biol Cell. 2000 Mar;11(3):915-27 [10712509] Mol Cell Biol. 2000 Apr;20(7):2367-77 [10713161] Mol Biol Cell. 2000 Apr;11(4):1293-304 [10749930] Mol Biol Cell. 2000 Apr;11(4):1305-13 [10749931] Genes Cells. 2000 Mar;5(3):221-33 [10759893] J Cell Biol. 2000 May 15;149(4):811-24 [10811823] Oncogene. 2000 Jun 1;19(24):2812-9 [10851084] Mol Cell Biol. 1991 Apr;11(4):2133-48 [1848673] Mol Cell Biol. 1991 Jun;11(6):3369-73 [1645449] J Cell Biol. 1993 Dec;123(6 Pt 2):1635-48 [8276886] Gene. 1994 May 27;143(1):135-8 [8200529] J Cell Biol. 1995 Mar;128(5):749-60 [7876302] Genes Dev. 1995 Mar 1;9(5):587-99 [7698648] Mol Biol Cell. 1995 Jul;6(7):793-807 [7579695] J Cell Biol. 1996 Apr;133(1):99-110 [8601617] EMBO J. 1996 May 1;15(9):2031-49 [8641269] Biochem Soc Trans. 1996 Feb;24(1):274-9 [8674685] Curr Biol. 1996 Dec 1;6(12):1599-608 [8994824] Nature. 1997 May 29;387(6632 Suppl):87-90 [9169871] Mech Dev. 1997 Jul;65(1-2):3-17 [9256341] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Cell. 1997 Oct 3;91(1):47-57 [9335334] Genes Dev. 1997 Dec 15;11(24):3375-86 [9407030] Genes Dev. 1998 Jul 1;12(13):1986-97 [9649503] Science. 1998 Oct 23;282(5389):754-9 [9784136] Genes Dev. 1999 Feb 1;13(3):320-33 [9990856] Bioessays. 1999 Jan;21(1):47-52 [10070253] Gene. 1999 Mar 18;229(1-2):109-16 [10095110] Nature. 1999 Jul 1;400(6739):37-42 [10403247] Cell. 1999 Jul 23;98(2):239-48 [10428035] Genes Dev. 1999 Sep 1;13(17):2271-83 [10485849] EMBO J. 1999 Oct 1;18(19):5334-46 [10508166] Trends Biochem Sci. 1997 Oct;22(10):374-6 [9357311] Cell. 1997 Nov 14;91(4):491-500 [9390558] Philos Trans R Soc Lond B Biol Sci. 1999 Sep 29;354(1389):1513-22 [10582237] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C-mediated down-regulation of beta(2)-adrenergic receptor and gene expression in rat C6 glioma cells. AN - 70815574; 11331411 AB - We investigated the regulation of beta(2)-adrenergic receptors (beta(2)AR) by protein kinase C (PKC) in rat C6 glioma cells at the levels of receptor activity, protein expression and gene expression. Cells exposed to 4beta-phorbol-12-myristate-13-acetate (PMA), a potent activator of PKC, exhibited a time- and concentration-dependent decrease in beta(2)AR binding activity. Maximum down-regulation was approximately 50% by 24 h and western blot analysis revealed a parallel decrease in beta(2)AR protein. In addition, PMA treatment resulted in an acute desensitization of beta(2)AR-stimulated cyclic AMP response prior to any reduction in receptor levels. PMA exposure also affected steady-state beta(2)AR mRNA levels in a time-dependent, biphasic manner. During the first 4 h, levels decreased by approximately 60% and then slowly recovered to approximately 75% of control by 24 h. As the reduction in receptor mRNA was not due to a decrease in its stability, we examined beta(2)AR gene transcription by nuclear run-on assays. Transcriptional activity in nuclei from C6 cells treated with PMA for 2 h was reduced by 70% compared to controls. Thus PKC can regulate beta(2)AR at least two levels: the first being an acute desensitization of receptor function, and the second being a more prolonged repression of receptor gene transcription that in turn results in decreased receptor expression. JF - Journal of neurochemistry AU - Leavitt, M AU - Setola, V AU - Fishman, P H AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892-4440, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 823 EP - 829 VL - 77 IS - 3 SN - 0022-3042, 0022-3042 KW - RNA, Messenger KW - 0 KW - Receptors, Adrenergic, beta-2 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Animals KW - Blotting, Western KW - Tumor Cells, Cultured KW - Kinetics KW - RNA, Messenger -- analysis KW - Enzyme Activation -- drug effects KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription, Genetic KW - Protein Kinase C -- metabolism KW - Down-Regulation KW - Gene Expression KW - Receptors, Adrenergic, beta-2 -- genetics KW - Glioma -- metabolism KW - Receptors, Adrenergic, beta-2 -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70815574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Protein+kinase+C-mediated+down-regulation+of+beta%282%29-adrenergic+receptor+and+gene+expression+in+rat+C6+glioma+cells.&rft.au=Leavitt%2C+M%3BSetola%2C+V%3BFishman%2C+P+H&rft.aulast=Leavitt&rft.aufirst=M&rft.date=2001-05-01&rft.volume=77&rft.issue=3&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An application of hierarchical regression in the investigation of multiple paternal occupational exposures and neuroblastoma in offspring. AN - 70804412; 11333409 AB - We used hierarchical regression to study the effects of 46 paternal occupational exposures on the incidence of neuroblastoma in offspring. The study population included 405 cases and 302 controls. The effect of each exposure was estimated using both conventional maximum likelihood and hierarchical regression. Using hierarchical regression, overall precision was greatly enhanced compared to the conventional analysis. In addition, adjustment of effect estimates based on prespecified prior distributions of the true effect parameters allowed a more consistent interpretation across the entire panel of exposures. Estimates for several metals and solvents were shrunk close to the null value, whereas estimates for several thinner solvents, diesel fuel, solders, wood dust, and grain dust remained moderately elevated. Hierarchical regression may mitigate some of the problems of the conventional approach by controlling for correlated exposures, enhancing the precision of estimates, and providing some adjustment of estimates based on prior knowledge. JF - American journal of industrial medicine AU - De Roos, A J AU - Poole, C AU - Teschke, K AU - Olshan, A F AD - Occupational Epidemiology Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892-7240, USA. deroosa@mail.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 477 EP - 486 VL - 39 IS - 5 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Regression Analysis KW - Humans KW - Adult KW - Incidence KW - Child KW - Male KW - Occupational Exposure KW - Paternal Exposure KW - Neuroblastoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70804412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=An+application+of+hierarchical+regression+in+the+investigation+of+multiple+paternal+occupational+exposures+and+neuroblastoma+in+offspring.&rft.au=De+Roos%2C+A+J%3BPoole%2C+C%3BTeschke%2C+K%3BOlshan%2C+A+F&rft.aulast=De+Roos&rft.aufirst=A&rft.date=2001-05-01&rft.volume=39&rft.issue=5&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validity of the CAGE Questionnaire in an American Indian Population AN - 61479367; 200200431 AB - This study evaluated the performance of the CAGE questionnaire (a set of four questions about alcoholism) in an American Indian population. We analyzed data from a cross-sectional study of 275 individuals (179 women) aged 21 years or older. Alcohol dependence was diagnosed according to the Diagnostic & Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R), based on a detailed psychiatric interview using the Schedule for Affective Disorders & Schizophrenia-Lifetime Version. Accuracy of the CAGE questionnaire was quantified as sensitivity, specificity, likelihood ratios, & the area under receiver operating characteristics (ROC) curves, using the DSM-III-R diagnosis as the reference. Of participants interviewed, 85% of men & 53% of women had a diagnosis of alcohol dependence by DSM-III-R. Findings suggest that the CAGE questionnaire is a valid screening method, in this population, for identifying people likely to have alcohol dependence. 5 Tables, 1 Figure, 32 References. Adapted from the source document. JF - Journal of Studies on Alcohol AU - Saremi, Aramesh AU - Hanson, Robert L AU - Williams, Desmond E AU - Roumain, Janine AU - Robin, Robert W AU - Long, Jeffrey C AU - Goldman, David AU - Knowler, William C AD - c/o Knowler -- National Instit Diabetes & Digestive & Kidney Diseases, Phoenix, AZ Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 294 EP - 300 VL - 62 IS - 3 SN - 0096-882X, 0096-882X KW - Questionnaires KW - Validity KW - Alcoholism KW - American Indians KW - article KW - 6129: addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61479367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Studies+on+Alcohol&rft.atitle=Validity+of+the+CAGE+Questionnaire+in+an+American+Indian+Population&rft.au=Saremi%2C+Aramesh%3BHanson%2C+Robert+L%3BWilliams%2C+Desmond+E%3BRoumain%2C+Janine%3BRobin%2C+Robert+W%3BLong%2C+Jeffrey+C%3BGoldman%2C+David%3BKnowler%2C+William+C&rft.aulast=Saremi&rft.aufirst=Aramesh&rft.date=2001-05-01&rft.volume=62&rft.issue=3&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JSALDP N1 - SubjectsTermNotLitGenreText - Alcoholism; American Indians; Validity; Questionnaires ER - TY - JOUR T1 - Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME) AN - 20141693; 10262878 AB - Hippocampal neurodegeneration and glia response was examined following administration of the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME). Male Long-Evans rats received L-NAME (50 mg/kg, ip) either once or twice a day for 4 days. Both dosing schedules decreased NOS activity by approximately 90%. At 10 and 30 days following cessation of L-NAME (2x/day), moderate neuronal death was evident in CA 1--2 pyramidal cells and dentate granule cells. Neurodegeneration was accompanied by increased astrocyte glial fibrillary acidic protein (GFAP) immunoreactivity yet, minimal astrocyte hypertrophy. Microglia response was limited to an increase in ramified microglia at 10 days, returning to normal by 30 days. As early as 4 days post-dosing (2x/day), GFAP mRNA levels were significantly elevated as were mRNA levels for tumor necrosis factor- alpha (TNF alpha ), interleukin-1 alpha (IL-1 alpha ), and interleukin 6 (IL-6). No alterations were seen with L-NAME dosing limited to once a day. The co-administration of a hippocampal neurotoxicant, trimethyltin (TMT), with the last dose of L-NAME (2x/day), produced an additive response pattern of neuronal degeneration including both CA1--2 and CA3--4 pyramidal neurons accompanied by TMT-induced astrocyte hypertrophy and prominent microglia reactivity. This was preceded by elevations in mRNA levels for GFAP, TNF alpha , IL-1 alpha , and IL-6 similar to those seen with each substance alone. These data suggest that high levels of L-NAME can produce a pro-inflammatory environment in the brain and that neurodegeneration and neuroglia responses in the hippocampus can be induced by an alteration in the balance and regulation of local nitric oxide levels. JF - Neurotoxicity Research AU - Harry, G Jean AU - Sills, Robert AU - Schlosser, Michael J AU - Maier, William E AD - National Institute for Environmental Health Sciences, Research Triangle Park, NC, USA, harry@niehs.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 307 EP - 319 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 3 IS - 3 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Interleukin 6 KW - Data processing KW - Astrocytes KW - NG-Nitroarginine methyl ester KW - Hippocampus KW - Interleukin 1 KW - Glial fibrillary acidic protein KW - Brain KW - Microglia KW - Neurodegeneration KW - mRNA KW - Inflammation KW - Nitric-oxide synthase KW - Granule cells KW - Nitroarginine KW - Hypertrophy KW - Immunoreactivity KW - Neurotoxicity KW - Glia KW - Trimethyltin KW - Nitric oxide KW - Tumor necrosis factor- alpha KW - Pyramidal cells KW - X 24500:Reviews, Legislation, Book & Conference Notices KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20141693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=Neurodegeneration+and+glia+response+in+rat+hippocampus+following+nitro-L-arginine+methyl+ester+%28L-NAME%29&rft.au=Harry%2C+G+Jean%3BSills%2C+Robert%3BSchlosser%2C+Michael+J%3BMaier%2C+William+E&rft.aulast=Harry&rft.aufirst=G&rft.date=2001-05-01&rft.volume=3&rft.issue=3&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033270 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Interleukin 6; Data processing; NG-Nitroarginine methyl ester; Astrocytes; Hippocampus; Interleukin 1; Brain; Glial fibrillary acidic protein; Microglia; Neurodegeneration; Inflammation; mRNA; Nitroarginine; Granule cells; Nitric-oxide synthase; Hypertrophy; Neurotoxicity; Immunoreactivity; Glia; Trimethyltin; Nitric oxide; Tumor necrosis factor- alpha; Pyramidal cells DO - http://dx.doi.org/10.1007/BF03033270 ER - TY - JOUR T1 - An analysis of the factory model for chromosome replication and segregation in bacteria AN - 18244841; 5308432 AB - Recent advances in microscopy have given us important clues as to the nature of chromosome segregation in bacteria. Most current observations favour the view that the process is co-replicational: DNA replication forks are anchored at the cell centre, and the newly replicated DNA is moved towards the cell poles. This scheme can account for orderly segregation even at high growth rates where multiple replication cycles overlap. We argue that there are five distinct activities directly involved in co-replicational segregation dynamics. These we refer to as Push, Direct, Condense, Hold and Clear. We attempt to assign one of these roles to each protein implicated in chromosome segregation. The proposed process is very different from mitosis in eukaryotic cells and perhaps more closely resembles the formation of separate sister chromatids during DNA replication. JF - Molecular Microbiology AU - Sawitzke, J AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, Division of Basic Sciences, NCI-Frederick, Frederick, MD 21702-1201, USA., austin@bncifcrf.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 786 EP - 794 PB - Blackwell Science Ltd VL - 40 IS - 4 SN - 0950-382X, 0950-382X KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Chromosomes KW - Replication KW - Reviews KW - Models KW - J 02725:DNA KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18244841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=An+analysis+of+the+factory+model+for+chromosome+replication+and+segregation+in+bacteria&rft.au=Sawitzke%2C+J%3BAustin%2C+S&rft.aulast=Sawitzke&rft.aufirst=J&rft.date=2001-05-01&rft.volume=40&rft.issue=4&rft.spage=786&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2001.02350.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Bacteria; Models; Chromosomes; Replication DO - http://dx.doi.org/10.1046/j.1365-2958.2001.02350.x ER - TY - JOUR T1 - Direct vertical electroelution of protein from a PhastSystem band for mass spectrometric identification at the level of a few picomoles AN - 18160419; 5142967 AB - An electroelution apparatus prototype of a new design was constructed. In that design, the electric field passes vertically through the protein band located on a horizontal (PhastSystem) minigel polymerized on a net of Gel-Fix (Serva). A simple, home-made apparatus allows for electroelution of protein bands at the level of a few picomoles and their identification, after concentration, by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The technique is applicable to one-dimensional (l-D) or two-dimensional (2-D) gels of any size, but has been exemplified only by application to 1-D minigels to demonstrate the lower limits of protein load of the method. When in the course of further development of the prototype it will be combined with a modification to two dimensions of the electroelution mechanism under computer control of the high-performance gel electrophoresis apparatus (formerly of LabIntelligence), the new design appears uniquely qualified for an automated spot elution from 2-D gels under avoidance of gel sectioning. JF - Proteomics AU - Buzas, Z AU - Chang, Huan-Tsung AU - Vieira, N E AU - Yergey, AL AU - Stastna, M AU - Chrambach, A AD - Bldg. 10, Rm. 9D50, NIH, Bethesda, MD 20892-1580, USA, acc@cu.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 691 EP - 698 VL - 1 IS - 5 SN - 1615-9853, 1615-9853 KW - electroelution KW - protein purification KW - proteomics KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Elution KW - Computer applications KW - Separation techniques KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18160419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Direct+vertical+electroelution+of+protein+from+a+PhastSystem+band+for+mass+spectrometric+identification+at+the+level+of+a+few+picomoles&rft.au=Buzas%2C+Z%3BChang%2C+Huan-Tsung%3BVieira%2C+N+E%3BYergey%2C+AL%3BStastna%2C+M%3BChrambach%2C+A&rft.aulast=Buzas&rft.aufirst=Z&rft.date=2001-05-01&rft.volume=1&rft.issue=5&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Separation techniques; Elution; Computer applications ER - TY - JOUR T1 - Physical activity and obesity: findings from cross-sectional and prospective studies AN - 18153095; 5148635 AB - Obesity results from an excessive energy intake or a low level of physical activity or both. Cross-sectional studies indicate that obese individuals are less active than their lean counterparts. However, whether a reduced physical activity is the cause or the consequence of obesity is unclear. We measured total energy expenditure (TEE, doubly labeled water) over 7 days in free-living conditions and sleeping metabolic rate over a few hours (SMR, indirect calorimetry) in a respiratory chamber in 91 mostly sedentary, adult, non-diabetic Pima Indians (63M/28F, 36 plus or minus 12 y, 35 plus or minus 10% body fat; mean plus or minus SD). Energy expenditure due to physical activity (EEACT) was calculated as (TEE - (SMR + 0.1* TEE)). Physical activity level (PAL) was calculated as TEE/SMR. Fat-free mass (FFM, kg) and fat mass (FM, kg) were measured at baseline by hydrodensitometry or DEXA. Baseline and follow-up body weights were available in 58 (36M/22F) of the 91 subjects. Cross-sectionally, both EEACT and PAL were negatively correlated with percent body fat (r = -0.22; p = 0.04 and r = -0.34; p < 0.01, respectively). In a multiple regression model, EEACT (993 plus or minus 316 kcal/d) was best predicted by the following equation (564 + 14 FFM - 6.4 FM - 5.1 age, R super(2) = 0.22; p < 0.01). PAL (1.80 plus or minus 0.23) was best predicted by the following equation (2.16-0.01 FM-0.003 age; R super(2) = 0.14, p < 0.01). In a prospective analysis, baseline EEACT and PAL were not correlated with body weight changes (which ranged from -6 to +20 kg over a follow-up of 3.4 plus or minus 2.6 y). This was still true after accounting for differences in baseline body composition and follow-up duration. Our cross-sectional data in an adult population at high risk for obesity confirm that increased adiposity is associated with reduced physical activity. Our prospective data, however, do not lend support to the hypothesis that a low level of physical activity is a major risk factor for the development of obesity in Pima Indians. JF - International Journal of Obesity AU - Tataranni, P A AU - Harper, I AU - DelParigi, A AU - Snitker, S AU - Ravussin, E AD - NIH-NIDDK, 4212 N. 16th St., Phoenix, AZ 85016, USA Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1 VL - 25 SN - 0307-0565, 0307-0565 KW - Physical Education Index KW - Men KW - Active and inactive persons KW - Exercise (effects) KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18153095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=Physical+activity+and+obesity%3A+findings+from+cross-sectional+and+prospective+studies&rft.au=Tataranni%2C+P+A%3BHarper%2C+I%3BDelParigi%2C+A%3BSnitker%2C+S%3BRavussin%2C+E&rft.aulast=Tataranni&rft.aufirst=P&rft.date=2001-05-01&rft.volume=25&rft.issue=&rft.spage=S17&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise (effects); Men; Active and inactive persons ER - TY - JOUR T1 - Cohort mortality study of Philadelphia firefighters AN - 18086324; 5172825 AB - Background: Fire fighters are exposed to a wide variety of toxic chemicals. Previous studies have reported excess risk of some cancers but have been limited by small numbers or little information on employment characteristics. Methods: We conducted a retrospective cohort mortality study among 7,789 Philadelphia firefighters employed between 1925 and 1986. For each cause of death, the standardized mortality ratios (SMRs) and 95% confidence intervals were estimated. We also compared mortality among groups of firefighters defined by the estimated number of career runs and potential for diesel exposure. Results: In comparison with U.S. white men, the firefighters had similar mortality from all causes of death combined (SMR = 0.96) and all cancers (SMR = 1.10). There were statistically significant deficits of deaths from nervous system diseases (SMR = 0.47), cerebrovascular diseases (SMR = 0.83), respiratory diseases (SMR = 0.67), genitourinary diseases (SMR = 0.54), all accidents (SMR = 0.72), and suicide (SMR = 0.66). Statistically significant excess risks were observed for colon cancer (SMR = 1.51) and ischemic heart disease (SMR = 1.09). The risks of mortality from colon cancer (SMR = 1.68), kidney cancer (SMR = 2.20), non-Hodgkin's lymphoma (SMR = 1.72), multiple myeloma (SMR = 2.31), and benign neoplasms (SMR = 2.54) were increased among firefighters with at least 20 years of service. Conclusions: Our study found no significant increase in overall mortality among Philadelphia firefighters. However, we observed increased mortality for cancers of the colon and kidney, non-Hodgkin's lymphoma and multiple myeloma. There was insufficient follow-up since the introduction of diesel equipment to adequately assess risk. JF - American Journal of Industrial Medicine AU - Baris, D AU - Garrity, T J AU - Telles, J L AU - Heineman, E F AU - Olshan, A AU - Zahm, SH AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd., EPS 8122, Bethesda, Maryland 20892, USA, barisd@mail.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 463 EP - 476 VL - 39 IS - 5 SN - 0271-3586, 0271-3586 KW - USA, Pennsylvania, Philadelphia KW - firefighter services KW - Health & Safety Science Abstracts; Risk Abstracts KW - Chemicals KW - Mortality KW - Toxic materials KW - Hazardous materials KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18086324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Cohort+mortality+study+of+Philadelphia+firefighters&rft.au=Baris%2C+D%3BGarrity%2C+T+J%3BTelles%2C+J+L%3BHeineman%2C+E+F%3BOlshan%2C+A%3BZahm%2C+SH&rft.aulast=Baris&rft.aufirst=D&rft.date=2001-05-01&rft.volume=39&rft.issue=5&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chemicals; Hazardous materials; Toxic materials; Occupational exposure; Mortality ER - TY - JOUR T1 - Patterns of mtDNA and microsatellite variation in an island and mainland population of guanacos in southern Chile AN - 18084305; 5172485 AB - The archaeological record indicates that guanacos inhabited the Patagonia of Chile and Argentina about 13,600 years ago, but were unable to migrate further south owing to the presence of glacial and water barriers that covered much of southern South America including the island of Tierra del Fuego. As environmental and ecological conditions improved, guanacos, along with other large mammals including horses, colonized the area. As a result of continued world-wide glacial melting, ocean levels rose and Tierra del Fuego became isolated from the mainland approximately 8000 years ago. Although island populations generally exhibit lower levels of genetic variation than their counterpart mainland populations, it is difficult to predict how much less variation island populations will exhibit. An analysis of mitochondrial cytochrome b and ATPase-8 sequences and 15 nuclear microsatellite loci revealed that both populations retained appreciable genetic diversity. The island population, however, exhibited much less variation than the mainland population. Measures of genetic variation revealed modest, but significant genetic differentiation, consistent with separation of the two populations approximately 8000 years ago. The assessment of levels of genetic diversity and population differentiation among populations of the wild South American camelids is becoming increasingly important as interest mounts in their utilization as a renewable resource. JF - Animal Conservation AU - Sarno, R J AU - Franklin, W L AU - O'Brien, S J AU - Johnson, W E AD - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702-1201, USA, rjsarno@mail.ncifcrf.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 93 EP - 101 VL - 4 IS - 2 SN - 1367-9430, 1367-9430 KW - Chile KW - guanacos KW - Tierra del Fuego KW - ATPase-8 gene KW - cytochrome b gene KW - Genetics Abstracts; Ecology Abstracts KW - Genetic isolation KW - Genetic diversity KW - Genetic distance KW - Ecological genetics KW - Lama guanicoe KW - G 07409:Ruminantia (nondomestic and camelids) KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18084305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Animal+Conservation&rft.atitle=Patterns+of+mtDNA+and+microsatellite+variation+in+an+island+and+mainland+population+of+guanacos+in+southern+Chile&rft.au=Sarno%2C+R+J%3BFranklin%2C+W+L%3BO%27Brien%2C+S+J%3BJohnson%2C+W+E&rft.aulast=Sarno&rft.aufirst=R&rft.date=2001-05-01&rft.volume=4&rft.issue=2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Animal+Conservation&rft.issn=13679430&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lama guanicoe; Genetic distance; Genetic diversity; Ecological genetics; Genetic isolation ER - TY - JOUR T1 - Structural Basis for the Activity and Substrate Specificity of Erwinia chrysanthemi L-Asparaginase AN - 18076401; 5139307 AB - Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been used for over 30 years as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Other substrates of asparaginases include L-glutamine, D-asparagine, and succinic acid monoamide. In this report, we present high-resolution crystal structures of the complexes of Erwinia chrysanthemi L-asparaginase (ErA) with the products of such reactions that also can serve as substrates, namely L-glutamic acid (L-Glu), D-aspartic acid (D-Asp), and succinic acid (Suc). Comparison of the four independent active sites within each complex indicates unique and specific binding of the ligand molecules; the mode of binding is also similar between complexes. The lack of the alpha -NH super(+) sub(3) group in Suc, compared to L-Asp, does not affect the binding mode. The side chain of L-Glu, larger than that of L-Asp, causes several structural distortions in the ErA active side. The active site flexible loop (residues 15-33) does not exhibit stable conformation, resulting in suboptimal orientation of the nucleophile, Thr15. Additionally, the delta -COO super(-) plane of L-Glu is approximately perpendicular to the plane of gamma -COO super(-) in L-Asp bound to the asparaginase active site. Binding of D-Asp to the ErA active site is very distinctive compared to the other ligands, suggesting that the low activity of ErA against D-Asp could be mainly attributed to the low k sub(cat) value. A comparison of the amino acid sequence and the crystal structure of ErA with those of other bacterial L-asparaginases shows that the presence of two active-site residues, Glu63 sub(ErA) and Ser254 sub(ErA), may correlate with significant glutaminase activity, while their substitution by Gln and Asn, respectively, may lead to minimal L-glutaminase activity. JF - Biochemistry (Washington) AU - Aghaiypour, K AU - Wlodawer, A AU - Lubkowski, J AD - Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA, jacek@ncifcrf.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 5655 EP - 5664 VL - 40 IS - 19 SN - 0006-2960, 0006-2960 KW - structure KW - Microbiology Abstracts B: Bacteriology KW - Asparaginase KW - Aspartic acid KW - Substrate specificity KW - Erwinia chrysanthemi KW - Asparagine KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18076401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Structural+Basis+for+the+Activity+and+Substrate+Specificity+of+Erwinia+chrysanthemi+L-Asparaginase&rft.au=Aghaiypour%2C+K%3BWlodawer%2C+A%3BLubkowski%2C+J&rft.aulast=Aghaiypour&rft.aufirst=K&rft.date=2001-05-01&rft.volume=40&rft.issue=19&rft.spage=5655&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Erwinia chrysanthemi; Asparagine; Aspartic acid; Substrate specificity; Asparaginase ER - TY - JOUR T1 - P1 and NR1 Plasmid Replication during the Cell Cycle of Escherichia coli AN - 17905482; 5145717 AB - Replication patterns of the miniP1 plasmid pZC176, the miniNR1 plasmid pRR933, and the high-copy miniNR1 derivative pRR942 were examined during the Escherichia coli cell division cycle and compared to the cycle-specific replication pattern of a minichromosome and the cycle nonspecific pattern of pBR322. In E. coli cells growing with doubling times of 40 and 60 min, the miniP1 plasmid was found to replicate with a slight periodicity during the division cycle. The periodicity was not nearly as pronounced as that of the minichromosome, was not affected by the presence of a minichromosome, and was not evident in cells growing more rapidly with a doubling time of 25 min. Both miniNR1 plasmids, pRR933 and pRR942, replicated with patterns indistinguishable from that of pBR322 and clearly different from that of the minichromosome. It is concluded that both P1 and NR1 plasmids can replicate at all stages of the cell cycle but that P1 displays a slight periodicity in replication probability in the cycle of slower growing cells. This periodicity does not appear to be coupled to a specific age in the cycle, but could be associated with the achievement of a specific cell mass per plasmid. During temperature shifts of a dnaC(Ts) mutant, the miniP1 plasmid and pBR322 replicated with similar patterns that differed from that of the minichromosome, but were consistent with a brief eclipse between rounds of replication. Copyright 2001 Academic Press. JF - Plasmid AU - Bogan, JA AU - Grimwade, JE AU - Thornton, M AU - Zhou, P AU - Denning, G D AU - Helmstetter, CE AD - Department of Biological Sciences, Florida Institute of Technology, Melbourne, Florida, 32901, bogan@box-b.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 200 EP - 208 PB - Academic Press VL - 45 IS - 3 SN - 0147-619X, 0147-619X KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Chromosomes KW - Cell cycle KW - Escherichia coli KW - Plasmids KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Plasmid&rft.atitle=P1+and+NR1+Plasmid+Replication+during+the+Cell+Cycle+of+Escherichia+coli&rft.au=Bogan%2C+JA%3BGrimwade%2C+JE%3BThornton%2C+M%3BZhou%2C+P%3BDenning%2C+G+D%3BHelmstetter%2C+CE&rft.aulast=Bogan&rft.aufirst=JA&rft.date=2001-05-01&rft.volume=45&rft.issue=3&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Plasmid&rft.issn=0147619X&rft_id=info:doi/10.1006%2Fplas.2000.1512 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Plasmids; Cell cycle; Chromosomes DO - http://dx.doi.org/10.1006/plas.2000.1512 ER - TY - JOUR T1 - Genotoxicity of pesticides: potential risk for consumers AN - 17900137; 5141788 AB - Pesticide residues in vegetables and fruits continue to generate concern in the general population mainly about their potential long term adverse effects such as cancer. The pesticides currently in use include a wide variety of compounds belonging to different chemical classes. More than 800 chemicals marketed as multiple formulations, are used in the European Union, as insecticides, herbicides, fungicides. Pesticides have been considered potential chemical mutagens. Experimental data revealed that various agrochemical ingredients possess mutagenic properties inducing gene mutation, chromosomal alteration or DNA damage. The genotoxic potential for agrochemical ingredients is generally low: they give positive results in few genotoxicity tests. In human biomonitoring studies genetic damage associated with pesticides has been detected for high exposure levels and intensive use. The genetic effects depend on quantity and variety of chemical formulations consumed. Improvements of agricultural practices and of safety of work conditions has reduced the genotoxic hazard. The most recent studies failed to reveal genotoxic damage. This evidence suggests a negligible risk for general population exposed to very low levels of residues. JF - Trends in Food Science & Technology AU - Bolognesi, C AU - Morasso, G AD - Toxicological Evaluation Unit, National Cancer Institute, Largo R. Benzi 10, 16132 Genoa, Italy, blgcld@hp380.ist.unige.it Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 182 EP - 187 VL - 11 IS - 4-5 SN - 0924-2244, 0924-2244 KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Fruits KW - Vegetables KW - Pesticide residues KW - Public health KW - Chromosome aberrations KW - Genotoxicity KW - Food contamination KW - Cancer KW - DNA damage KW - Reviews KW - Pesticides KW - H 5000:Pesticides KW - R2 23060:Medical and environmental health KW - W2 32000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17900137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Food+Science+%26+Technology&rft.atitle=Genotoxicity+of+pesticides%3A+potential+risk+for+consumers&rft.au=Bolognesi%2C+C%3BMorasso%2C+G&rft.aulast=Bolognesi&rft.aufirst=C&rft.date=2001-05-01&rft.volume=11&rft.issue=4-5&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Trends+in+Food+Science+%26+Technology&rft.issn=09242244&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticide residues; Genotoxicity; Cancer; Chromosome aberrations; Public health; Food contamination; Pesticides; Reviews; Risk assessment; Vegetables; Fruits; DNA damage ER - TY - JOUR T1 - Mono-(2-ethylhexyl) Phthalate Suppresses Aromatase Transcript Levels and Estradiol Production in Cultured Rat Granulosa Cells AN - 17895505; 5130601 AB - The female reproductive toxicity of di-(2-ethylhexyl) phthalate and its active metabolite mono-(2-ethylhexyl) phthalate (MEHP) is attributed to suppression of ovarian granulosa cell estradiol production. In these studies, several structurally related phthalates (0-200 mu M) and Wy-14,643 (0-100 mu M) were compared to MEHP for their effects on granulosa cell estradiol production and transcript levels of cytochrome P450 enzyme CYP 19, also known as aromatase (P450arom), the rate-limiting enzyme in the conversion of androgens to estrogens. Granulosa cells were obtained from 28-day-old Fisher 344 rats and were cultured for 48 h. Test chemical or DMSO was added at the time of culture, along with testosterone as a substrate for aromatase. 17 beta -Estradiol production was measured by standard radioimmunoassay, mRNA was measured by fluorescent RT-PCR, and protein was measured by Western blot analysis. MEHP was unique among the phthalates in its ability to decrease estradiol production, while Wy-14,643 had effects similar to MEHP at 100 mu M. MEHP and Wy-14,643 also significantly decreased aromatase mRNA levels. The decrease in mRNA was concentration dependent and was paralleled by a decrease in aromatase protein. MEHP did not alter levels of CYP 11A1, the cholesterol side-chain cleavage enzyme (P450scc). Treatment with a cAMP analogue increased expression of P450scc in the presence of MEHP (100 to 200 mu M) while the decrease in aromatase remained. Thus, these studies suggest that MEHP is distinct from several structurally related phthalates but similar to the peroxisome proliferator Wy-14,643 in its action on granulosa cell estradiol production. Moreover, the suppression of estradiol by MEHP is likely mediated through its action on aromatase transcript levels independent of cAMP-stimulated regulation. Copyright 2001 Academic Press. JF - Toxicology and Applied Pharmacology AU - Lovekamp, T N AU - Davis, B J AD - Laboratory of Womens Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, Davis1@niehs.nih.gov Y1 - 2001/05/01/ PY - 2001 DA - 2001 May 01 SP - 217 EP - 224 PB - Academic Press VL - 172 IS - 3 SN - 0041-008X, 0041-008X KW - rats KW - mono(2-ethylhexyl phthalate KW - Toxicology Abstracts KW - Granulosa cells KW - Aromatase KW - Estradiol KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Mono-%282-ethylhexyl%29+Phthalate+Suppresses+Aromatase+Transcript+Levels+and+Estradiol+Production+in+Cultured+Rat+Granulosa+Cells&rft.au=Lovekamp%2C+T+N%3BDavis%2C+B+J&rft.aulast=Lovekamp&rft.aufirst=T&rft.date=2001-05-01&rft.volume=172&rft.issue=3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2001.9156 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aromatase; Granulosa cells; Estradiol DO - http://dx.doi.org/10.1006/taap.2001.9156 ER - TY - JOUR T1 - Molecular Mimicry and Antigen-Specific T Cell Responses in Multiple Sclerosis and Chronic CNS Lyme Disease AN - 17888378; 5130769 AB - The concept of molecular mimicry provides and elegant framework as to how cross-reactivity between antigens from a foreign agent with self proteins may trigger autoimmune diseases. While it was previously thought that sequence and structural homology between foreign and self proteins or the sharing of T cell receptor (TCR) and MHC-binding motifs are required for molecular mimicry to occur, we have shown that even completely unrelated peptide sequences may lead to cross-recognition by T cells. The use of synthetic combinatorial peptide libraries in the positional scanning format (PS-SCL) together with novel biometric prediction approaches has allowed us to describe the recognition profiles of individual autoreactive T cell clones (TCC) with unprecedented accuracy. Through studies of myelin-specific TCC as well as clones from the nervous system of patients suffering from chronic central nervous (CNS) Lyme disease it has become clear that at least some T cells are more degenerate than previously anticipated. These data will not only help us to redefine what constitutes specific T cell recognition, but also allow us to study in more detail the biological role of molecular mimicry. A recent clinical trial with an altered peptide ligand (APL) of one of the candidate myelin basic protein (MBP) epitopes in MS (amino acids 83-99) has shown that such a modified MBP peptide may not only have therapeutic efficacy, but also bears the potential to exacerbate disease. Thus, we provide firm evidence that the basic principles of cross-recognition and their pathogenetic significance are relevant in MS. Copyright 2001 Academic Press JF - Journal of Autoimmunity AU - Martin, R AU - Gran, B AU - Zhao, Y AU - Markovic-Plese, S AU - Bielekova, B AU - Marques, A AU - Sung, M AU - Hemmer, B AU - Simon, R AU - McFarland, H F AU - Pinilla, C AD - Neuroimmunology Branch, NINDS, NIH Building, 10 Room 5B-16, 10 Center DR MSC 1400, Bethesda, MD, 20892-1400, USA, martinr@ninds.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 187 EP - 192 PB - Academic Press VL - 16 IS - 3 SN - 0896-8411, 0896-8411 KW - man KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Central nervous system KW - Multiple sclerosis KW - Borrelia burgdorferi KW - Autoimmune diseases KW - Lymphocytes T KW - Lyme disease KW - F 068765:Multiple sclerosis KW - J 02833:Immune response and immune mechanisms KW - J 02848:Nervous system KW - F 06756:Function UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17888378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Autoimmunity&rft.atitle=Molecular+Mimicry+and+Antigen-Specific+T+Cell+Responses+in+Multiple+Sclerosis+and+Chronic+CNS+Lyme+Disease&rft.au=Martin%2C+R%3BGran%2C+B%3BZhao%2C+Y%3BMarkovic-Plese%2C+S%3BBielekova%2C+B%3BMarques%2C+A%3BSung%2C+M%3BHemmer%2C+B%3BSimon%2C+R%3BMcFarland%2C+H+F%3BPinilla%2C+C&rft.aulast=Martin&rft.aufirst=R&rft.date=2001-05-01&rft.volume=16&rft.issue=3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Journal+of+Autoimmunity&rft.issn=08968411&rft_id=info:doi/10.1006%2Fjaut.2000.0501 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Lymphocytes T; Lyme disease; Central nervous system; Autoimmune diseases; Multiple sclerosis DO - http://dx.doi.org/10.1006/jaut.2000.0501 ER - TY - JOUR T1 - 4'-Ethynyl Nucleoside Analogs: Potent Inhibitors of Multidrug-Resistant Human Immunodeficiency Virus Variants In Vitro AN - 17880519; 5117525 AB - A series of 4'-ethynyl (4'-E) nucleoside analogs were designed, synthesized, and identified as being active against a wide spectrum of human immunodeficiency viruses (HIV), including a variety of laboratory strains of HIV-1, HIV-2, and primary clinical HIV-1 isolates. Among such analogs examined, 4'-E-2'-deoxycytidine (4'-E-dC), 4'-E-2'-deoxyadenosine (4'-E-dA), 4'-E-2'-deoxyribofuranosyl-2,6-diaminopurine, and 4'-E-2'-deoxyguanosine were the most potent and blocked HIV-1 replication with 50% effective concentrations ranging from 0.0003 to 0.01 mu M in vitro with favorable cellular toxicity profiles (selectivity indices ranging 458 to 2,600). These 4'-E analogs also suppressed replication of various drug. resistant HIV-1 clones, including HIV-1 sub(M41L/T215Y), HIV-1 sub(K65R), HIV-1 sub(L74V), HIV-1 sub(M41L/T69S-S-G/T215Y), and HIV-1 sub(A62V/V75I/F77L/F116Y/Q151M). Moreover, these analogs inhibited the replication of multidrug-resistant clinical HIV-1 strains carrying a variety of drug resistance-related amino acid substitutions isolated from HIV-1-infected individuals for whom 10 or 11 different anti-HIV-1 agents had failed. The 4'-E analogs also blocked the replication of a non-nucleoside reverse transcriptase inhibitor-resistant clone, HIV-1 sub(Y181C), and showed an HIV-1 inhibition profile similar to that of zidovudine in time-of-drug-addition assays. The antiviral activity of 4'-E-thymidine and 4'-E-dC was blocked by the addition of thymidine and 2'-deoxycytidine, respectively, while that of 4'-E-dA was not affected by 2'-deoxyadenosine, similar to the antiviral activity reversion feature of 2',3'-dideoxynucleosides, strongly suggesting that 4'-E analogs belong to the family of nucleoside reverse transcriptase inhibitors. Further development of 4'-E analogs as potential therapeutics for infection with multidrug-resistant HIV-1 is warranted. JF - Antimicrobial Agents & Chemotherapy AU - Kodama, Ei-Ichi AU - Kohgo, Satoru AU - Kitano, Kenji AU - Machida, Haruhiko AU - Gatanaga, Hiroyuki AU - Shigeta, Shiro AU - Matsuoka, Masao AU - Ohrui, Hiroshi AU - Mitsuya, Hiroaki AD - Medicine Branch, Building 10, Room 5A11, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA, hmitsuya@helix.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1539 EP - 1546 VL - 45 IS - 5 SN - 0066-4804, 0066-4804 KW - HIV-1 KW - 4-Ethynyl nucleosides KW - nucleoside analogues KW - nucleosides KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Antiviral agents KW - Drug resistance KW - Human immunodeficiency virus 1 KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17880519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=4%27-Ethynyl+Nucleoside+Analogs%3A+Potent+Inhibitors+of+Multidrug-Resistant+Human+Immunodeficiency+Virus+Variants+In+Vitro&rft.au=Kodama%2C+Ei-Ichi%3BKohgo%2C+Satoru%3BKitano%2C+Kenji%3BMachida%2C+Haruhiko%3BGatanaga%2C+Hiroyuki%3BShigeta%2C+Shiro%3BMatsuoka%2C+Masao%3BOhrui%2C+Hiroshi%3BMitsuya%2C+Hiroaki&rft.aulast=Kodama&rft.aufirst=Ei-Ichi&rft.date=2001-05-01&rft.volume=45&rft.issue=5&rft.spage=1539&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Antiviral agents; Drug resistance ER - TY - JOUR T1 - Tolerance and Pharmacokinetic Interactions of Rifabutin and Azithromycin AN - 17878941; 5117533 AB - This multicenter study evaluated the tolerance and potential pharmacokinetic interactions between azithromycin and rifabutin in volunteers with or without human immunodeficiency virus infection. Daily dosing with the combination of azithromycin and rifabutin was poorly tolerated, primarily because of gastrointestinal symptoms and neutropenia. No significant pharmacokinetic interactions were found between these drugs. JF - Antimicrobial Agents & Chemotherapy AU - Hafner, R AU - Bethel, J AU - Standiford, H C AU - Follansbee, S AU - Cohn, D L AU - Polk, R E AU - Mole, L AU - Raasch, R AU - Kumar, P AU - Mushatt, D AU - Drusano, G AD - Division of AIDS, NIAID, 6700-B Rockledge Dr.-MSC 7624, Bethesda, MD 20892-7624, USA, RHafner@niaid.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 1572 EP - 1577 VL - 45 IS - 5 SN - 0066-4804, 0066-4804 KW - man KW - HIV KW - Virology & AIDS Abstracts; Toxicology Abstracts KW - Acquired immune deficiency syndrome KW - Rifabutin KW - Pharmacokinetics KW - Human immunodeficiency virus KW - Azithromycin KW - Drugs KW - Side effects KW - X 24114:Metabolism KW - V 22006:AIDS: Other aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17878941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Tolerance+and+Pharmacokinetic+Interactions+of+Rifabutin+and+Azithromycin&rft.au=Hafner%2C+R%3BBethel%2C+J%3BStandiford%2C+H+C%3BFollansbee%2C+S%3BCohn%2C+D+L%3BPolk%2C+R+E%3BMole%2C+L%3BRaasch%2C+R%3BKumar%2C+P%3BMushatt%2C+D%3BDrusano%2C+G&rft.aulast=Hafner&rft.aufirst=R&rft.date=2001-05-01&rft.volume=45&rft.issue=5&rft.spage=1572&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Pharmacokinetics; Acquired immune deficiency syndrome; Side effects; Drugs; Azithromycin; Rifabutin ER - TY - JOUR T1 - Searching for array standards in Rockville. A recent US NIH meeting produced a draft pilot protocol to facilitate microarray data sharing AN - 17877428; 5118914 AB - Twenty-three research groups funded by microarray initiatives at the National Institute on Drug Abuse (NIDA) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the US National Institutes of Health (NIH; Rockville, MD) recently took part in a meeting to discuss current logistical challenges in microarray research and formulate a strategy for facilitating progress in the field. After extensive discussion, a plan was proposed incorporating the establishment of effective communication tools, use of a standard subset of several hundred genes, adoption of a single gene-naming protocol, design of a set of standard quality controls, and the development of a control pool of RNA, together with the requisite bioinformatics tools. The US National Center for Biotechnology Information (NCBI; Rockville, MD) Gene Expression Omnibus (GEO) was suggested as an ideal repository for microarray data. We believe that such an arrangement could serve as a model for other national/international microarray data curation/storage efforts. JF - Nature Biotechnology AU - Star, R A AU - Rasooly, R S AD - Cell Biology & Genetics at the Division of Neuroscience & Behavioral Research, National Institute on Drug Abuse/NIH, Bethesda, MD 20892-9555, USA, rrasooly@nida.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 418 EP - 419 VL - 19 IS - 5 SN - 1087-0156, 1087-0156 KW - NCBI KW - NIDA KW - NIDDK KW - NIH KW - data sharing KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Reviews KW - Government policy KW - Bioinformatics KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17877428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Searching+for+array+standards+in+Rockville.+A+recent+US+NIH+meeting+produced+a+draft+pilot+protocol+to+facilitate+microarray+data+sharing&rft.au=Star%2C+R+A%3BRasooly%2C+R+S&rft.aulast=Star&rft.aufirst=R&rft.date=2001-05-01&rft.volume=19&rft.issue=5&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Government policy; Reviews ER - TY - JOUR T1 - Comparative Xenobiotic Metabolism between Tg.AC and p53+/- Genetically Altered Mice and Their Respective Wild Types AN - 17874761; 5121959 AB - The use of transgenic animals, such as v-Ha-ras activated (Tg.AC) and p53+/-mice, offers great promise for a rapid and more sensitive assay for chemical carcinogenicity. Some carcinogens are metabolically activated; therefore, it is critical that the altered genome of either of these model systems does not compromise their capability and capacity for metabolism of xenobiotics. The present work tests the generally held assumption that xenobiotic metabolism in the Tg.AC and p53+/- mouse is not inherently different from that of the respective wild type, the FVB/N and C57BL/6 mouse, by comparing each genotype's ability to metabolize benzene, ethoxyquin, or methacrylonitrile. Use of these representative substrates offers the opportunity to examine arene oxide formation, aromatic ring opening, hydroxylation, epoxidation, O-deethylation, and a number of conjugation reactions. Mice were treated by gavage with super(14)C-labeled parent compound, excreta were collected, and elimination routes and rates, as well as super(14)C-derived metabolite profiles in urine, were compared between relevant treatment groups. Results of this study indicated that metabolism of the 3 parent compounds was not appreciably altered between either FVB/N and Tg.AC mice or C57BL/6 and p53+/- mice. Further, expression of CYP1A2, CYP2E1, CYP3A, and GST- alpha in liver of naive genetically altered mice was similar to that of corresponding wild-type mice. Thus, these results suggest that the inherent ability of Tg.AC and p53+/- mice to metabolize xenobiotics is not compromised by their altered genomes and would not be a factor in data interpretation of toxicity studies using either transgenic mouse line. JF - Toxicological Sciences AU - Sanders, J M AU - Burka, L T AU - Chanas, B AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, MD C3-02, P.O. Box 12233, Research Triangle Park, NC 27709-2233 ,USA Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 54 EP - 61 VL - 61 IS - 1 SN - 1096-6080, 1096-6080 KW - metabolism KW - ethoxyquin KW - methacrylonitrile KW - Toxicology Abstracts KW - Carcinogenicity testing KW - Xenobiotics KW - Transgenic mice KW - Benzene KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17874761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Comparative+Xenobiotic+Metabolism+between+Tg.AC+and+p53%2B%2F-+Genetically+Altered+Mice+and+Their+Respective+Wild+Types&rft.au=Sanders%2C+J+M%3BBurka%2C+L+T%3BChanas%2C+B%3BMatthews%2C+H+B&rft.aulast=Sanders&rft.aufirst=J&rft.date=2001-05-01&rft.volume=61&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenicity testing; Transgenic mice; Benzene; Xenobiotics ER - TY - JOUR T1 - Chlamydia pneumoniae Major Outer Membrane Protein Is a Surface-Exposed Antigen That Elicits Antibodies Primarily Directed against Conformation-Dependent Determinants AN - 17847262; 4875029 AB - The major outer membrane protein (MOMP) of Chlamydia trachomatis serovariants is known to be an immunodominant surface antigen. Moreover, it is known that the C. trachomatis MOMP elicits antibodies that recognize both linear and conformational antigenic determinants. In contrast, it has been reported that the MOMP of Chlamydia pneumoniae is not surface exposed and is immunorecessive. We hypothesized that the discrepancies between C. trachomatis and C. pneumoniae MOMP exposure on intact chlamydiae and immunogenic properties might be because the focus of the host's immune response is directed to conformational epitopes of the C. pneumoniae MOMP. We therefore conducted studies aimed at defining the surface exposure of MOMP and the conformational dominance of MOMP antibodies. We present here a description of C. pneumoniae species-specific monoclonal antibody (MAb), GZD1E8, which recognizes a conformational epitope on the surface of C. pneumoniae. This MAb is potent in the neutralization of C. pneumoniae infectivity in vitro. Another previously described C. pneumoniae species-specific monoclonal antibody, RR-402, displayed very similar characteristics. However, the antigenic determinant recognized by RR-402 has yet to be identified. We show by immunoprecipitation of C. pneumoniae with GZD1E8 and RR-402 MAbs and by mass spectrometry analysis of immunoprecipitated proteins that both antibodies GZD1E8 and RR-402 recognize the MOMP of C. pneumoniae and that this protein is localized on the surface of the organism. We also show that human sera from C. pneumoniae-positive donors consistently recognize the MOMP by immunoprecipitation, indicating that the MOMP of C. pneumoniae is an immunogenic protein. These findings have potential implications for both C. pneumoniae vaccine and diagnostic assay development. JF - Infection and Immunity AU - Wolf, K AU - Fischer, E AU - Mead, D AU - Zhong, G AU - Peeling, R AU - Whitmire, B AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, 900 South 4th St., Hamilton, MT 59840, kwolf@niaid.nih.gov Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 3082 EP - 3091 VL - 69 IS - 5 SN - 0019-9567, 0019-9567 KW - man KW - Chlamydia trachomatis KW - GZD1E8 antigen KW - RR-402 antigen KW - major outer membrane protein KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Monoclonal antibodies KW - Chlamydia pneumoniae KW - Outer membranes KW - Immunoprecipitation KW - Vaccines KW - Antibody response KW - Membrane proteins KW - J 02832:Antigenic properties and virulence KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17847262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Chlamydia+pneumoniae+Major+Outer+Membrane+Protein+Is+a+Surface-Exposed+Antigen+That+Elicits+Antibodies+Primarily+Directed+against+Conformation-Dependent+Determinants&rft.au=Wolf%2C+K%3BFischer%2C+E%3BMead%2C+D%3BZhong%2C+G%3BPeeling%2C+R%3BWhitmire%2C+B%3BCaldwell%2C+H+D&rft.aulast=Wolf&rft.aufirst=K&rft.date=2001-05-01&rft.volume=69&rft.issue=5&rft.spage=3082&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.5.3082-3091.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Chlamydia pneumoniae; Monoclonal antibodies; Outer membranes; Membrane proteins; Antibody response; Vaccines; Immunoprecipitation DO - http://dx.doi.org/10.1128/IAI.69.5.3082-3091.2001 ER - TY - JOUR T1 - Molecular profiling of tissue samples using laser capture microdissection AN - 1367481962; 16579343 AB - The management of cancer and other genetically based diseases is far from optimal in even our most advanced medical centers. There is still uncertainty regarding how diseases will progress in certain patients, toxicity that must be tolerated with imprecise treatment regimens and significant potential for treatment failure. As our understanding of the complexity of these diseases has increased, it has become clear that we must move toward precisely tailored approaches to treating each individual patient. To that end, a major goal of current medical research is the rapid identification of the specific molecular alterations in each patient's disease. This will enable the design of optimal diagnosis, prognosis and treatment, significantly improving survival. This review describes one important approach to the genetic analysis of disease - molecular profiling - and the tenets and technologies necessary for its success. JF - Expert Review of Molecular Diagnostics AU - Best, Carolyn JM AU - Emmert-Buck, Michael R AD - Pathogenetics Unit, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2001/05// PY - 2001 DA - May 2001 SP - 53 EP - 60 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 1 IS - 1 SN - 1473-7159, 1473-7159 KW - Toxicology Abstracts KW - Reviews KW - Genetic analysis KW - Prognosis KW - Survival KW - Lasers KW - Toxicity KW - Cancer KW - X 24390:Radioactive Materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1367481962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Review+of+Molecular+Diagnostics&rft.atitle=Molecular+profiling+of+tissue+samples+using+laser+capture+microdissection&rft.au=Best%2C+Carolyn+JM%3BEmmert-Buck%2C+Michael+R&rft.aulast=Best&rft.aufirst=Carolyn&rft.date=2001-05-01&rft.volume=1&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Expert+Review+of+Molecular+Diagnostics&rft.issn=14737159&rft_id=info:doi/10.1586%2F14737159.1.1.53 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-06-01 N1 - Last updated - 2013-07-15 N1 - SubjectsTermNotLitGenreText - Reviews; Genetic analysis; Prognosis; Survival; Lasers; Toxicity; Cancer DO - http://dx.doi.org/10.1586/14737159.1.1.53 ER - TY - JOUR T1 - Rapid cycling of lipid raft markers between the cell surface and Golgi complex. AN - 70832991; 11331304 AB - The endocytic itineraries of lipid raft markers, such as glycosyl phosphatidylinositol (GPI)-anchored proteins and glycosphingolipids, are incompletely understood. Here we show that different GPI-anchored proteins have different intracellular distributions; some (such as the folate receptor) accumulate in transferrin-containing compartments, others (such as CD59 and GPI-linked green fluorescent protein [GFP]) accumulate in the Golgi apparatus. Selective photobleaching shows that the Golgi pool of both GPI-GFP and CD59-GFP constantly and rapidly exchanges with the pool of these proteins found on the plasma membrane (PM). We visualized intermediates carrying GPI-GFP from the Golgi apparatus to the PM and separate structures delivering GPI-GFP to the Golgi apparatus.GPI-GFP does not accumulate within endocytic compartments containing transferrin, although it is detected in intracellular structures which are endosomes by the criteria of accessibility to a fluid phase marker and to cholera and shiga toxin B subunits (CTxB and STxB, which are also found in rafts). GPI-GFP and a proportion of the total CTxB and STxB taken up into cells are endocytosed independently of clathrin-associated machinery and are delivered to the Golgi complex via indistinguishable mechanisms. Hence, they enter the Golgi complex in the same intermediates, get there independently of both clathrin and rab5 function, and are excluded from it at 20 degrees C and under conditions of cholesterol sequestration. The PM-Golgi cycling pathway followed by GPI-GFP could serve to regulate lipid raft distribution and function within cells. JF - The Journal of cell biology AU - Nichols, B J AU - Kenworthy, A K AU - Polishchuk, R S AU - Lodge, R AU - Roberts, T H AU - Hirschberg, K AU - Phair, R D AU - Lippincott-Schwartz, J AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20895, USA. Y1 - 2001/04/30/ PY - 2001 DA - 2001 Apr 30 SP - 529 EP - 541 VL - 153 IS - 3 SN - 0021-9525, 0021-9525 KW - Antigens, CD59 KW - 0 KW - Clathrin KW - Glycosylphosphatidylinositols KW - Luminescent Proteins KW - Shiga Toxins KW - Transferrin KW - stxB toxin KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Cholera Toxin KW - 9012-63-9 KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Clathrin -- metabolism KW - Biological Transport KW - Exocytosis KW - Luminescent Proteins -- metabolism KW - Shiga Toxins -- metabolism KW - Transferrin -- metabolism KW - Microscopy, Fluorescence KW - Antigens, CD59 -- metabolism KW - Photomicrography KW - Cell Compartmentation KW - Glycosylphosphatidylinositols -- metabolism KW - Cholera Toxin -- metabolism KW - Membrane Microdomains -- metabolism KW - Cell Membrane -- metabolism KW - Golgi Apparatus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70832991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Rapid+cycling+of+lipid+raft+markers+between+the+cell+surface+and+Golgi+complex.&rft.au=Nichols%2C+B+J%3BKenworthy%2C+A+K%3BPolishchuk%2C+R+S%3BLodge%2C+R%3BRoberts%2C+T+H%3BHirschberg%2C+K%3BPhair%2C+R+D%3BLippincott-Schwartz%2C+J&rft.aulast=Nichols&rft.aufirst=B&rft.date=2001-04-30&rft.volume=153&rft.issue=3&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1990 Mar;110(3):637-49 [1968465] J Cell Biol. 1989 Apr;108(4):1331-43 [2564398] Biochem Int. 1990 Oct;22(1):85-94 [2282082] J Cell Biol. 1993 Jun;121(5):1031-9 [7684737] Science. 1993 Sep 3;261(5126):1280-1 [8362242] Immunol Res. 1993;12(3):258-75 [7507156] EMBO J. 1994 Mar 15;13(6):1287-96 [8137813] J Cell Biol. 1994 May;125(4):769-81 [8188745] J Cell Biol. 1994 Dec;127(5):1199-215 [7962085] J Biol Chem. 1995 Sep 8;270(36):21271-6 [7673162] Glycobiology. 1995 Jun;5(4):407-15 [7579795] Mol Biol Cell. 1995 Jul;6(7):929-44 [7579703] J Cell Biol. 1996 Sep;134(5):1169-77 [8794859] J Biol Chem. 1996 Sep 27;271(39):24048-54 [8798641] J Biol Chem. 1997 May 23;272(21):13929-36 [9153255] Nature. 1997 Jun 5;387(6633):569-72 [9177342] J Cell Biol. 1997 Dec 15;139(6):1447-54 [9396750] Am J Physiol. 1998 Feb;274(2 Pt 1):C319-32 [9486120] J Cell Biol. 1998 Mar 23;140(6):1357-67 [9508769] J Cell Biol. 1998 May 18;141(4):905-15 [9585410] J Cell Biol. 1998 Jul 13;142(1):69-84 [9660864] EMBO J. 1998 Aug 17;17(16):4626-38 [9707422] Nature. 1998 Aug 20;394(6695):793-7 [9723620] Nature. 1998 Aug 20;394(6695):798-801 [9723621] J Cell Biol. 1998 Aug 24;142(4):923-36 [9722606] J Cell Biol. 1998 Nov 16;143(4):973-90 [9817755] J Cell Biol. 1998 Dec 14;143(6):1485-503 [9852146] Annu Rev Cell Dev Biol. 1998;14:111-36 [9891780] J Cell Sci. 1999 May;112 ( Pt 9):1303-11 [10194409] J Cell Biol. 1999 Jul 26;146(2):313-20 [10427087] J Cell Sci. 1999 Nov;112 ( Pt 22):3899-909 [10547351] J Biol Chem. 1999 Dec 3;274(49):35278-82 [10575015] Cell. 1999 Dec 10;99(6):589-601 [10612395] J Cell Biol. 2000 Jan 10;148(1):45-58 [10629217] J Cell Biol. 2000 Mar 6;148(5):997-1008 [10704449] Nat Cell Biol. 2000 May;2(5):288-95 [10806480] J Cell Biol. 1988 Feb;106(2):253-67 [2892843] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7419-23 [2145577] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Understanding the experience of pain in terminally ill patients. AN - 70836018; 11343734 AB - Terminally ill patients commonly experience substantial pain. Unresolved pain has been cited as evidence that end-of-life care is of poor quality. However, the data on which that conclusion is based are limited. We aimed to provide additional data on the experience of pain in such patients. We interviewed 988 terminally ill patients from six randomly selected US sites. We asked them who had treated their pain in the previous 4 weeks (primary-care physician, pain specialist, or both), and whether they wanted more pain medication than they were receiving, or why they did not want more. 496 (50%) terminally ill patients reported moderate or severe pain. 514 (52%) individuals had seen a primary-care physician for treatment of pain in the previous 4 weeks and 198 (20%) saw a pain specialist. Of those who had been treated by their primary-care physician, 287 (29%) wanted more therapy, 613 (62%) wanted their pain therapy to remain the same, and 89 (9%) wanted to reduce or stop their pain therapy. Several reasons for not wanting additional therapy were offered-fear of addiction, dislike of mental or physical side-effects, and not wanting to take more pills or injections. We saw no association between disease and amount of pain between disease and the desire for more treatment. Black patients were more likely to seek additional pain therapy, see a pain specialist, and refuse additional medication because of fear of addiction than other populations. Although half of terminally ill patients experienced moderate to severe pain, only 30% of them wanted additional pain treatment from their primary-care physician. The number of patients experiencing pain remains too high. However, the number is not as large as perceived. Additionally, most are willing to tolerate pain. Furthermore, the experience of pain is constant across major terminal diseases. JF - Lancet (London, England) AU - Weiss, S C AU - Emanuel, L L AU - Fairclough, D L AU - Emanuel, E J AD - Department of Clinical Bioethics, Warren G Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C118, Bethesda, MD 20892, USA. sweiss@nih.gov Y1 - 2001/04/28/ PY - 2001 DA - 2001 Apr 28 SP - 1311 EP - 1315 VL - 357 IS - 9265 SN - 0140-6736, 0140-6736 KW - Analgesics KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Chi-Square Distribution KW - Humans KW - Aged KW - Pain Measurement KW - Socioeconomic Factors KW - Logistic Models KW - Adult KW - Interviews as Topic KW - Middle Aged KW - Female KW - Male KW - Treatment Refusal -- psychology KW - Terminal Care KW - Pain -- drug therapy KW - Pain -- psychology KW - Palliative Care KW - Analgesics -- therapeutic use KW - Analgesics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70836018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Understanding+the+experience+of+pain+in+terminally+ill+patients.&rft.au=Weiss%2C+S+C%3BEmanuel%2C+L+L%3BFairclough%2C+D+L%3BEmanuel%2C+E+J&rft.aulast=Weiss&rft.aufirst=S&rft.date=2001-04-28&rft.volume=357&rft.issue=9265&rft.spage=1311&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 2001 Sep 22;358(9286):1014-5 [11583773] Lancet. 2001 Apr 28;357(9265):1304-5 [11343728] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditional liver-specific expression of simian virus 40 T antigen leads to regulatable development of hepatic neoplasm in transgenic mice. AN - 70788053; 11278564 AB - Adaptive epigenetic changes and toxicity often accompany constitutive expression of a transgene or knockout of an endogenous gene in mice. These considerations potentially limit the usefulness of transgenic technology in studying the in vivo functions of a gene. Using conditional gene expression technology, it is possible to override such restrictions to achieve temporal and tissue-specific manipulation of gene expression in vivo. Based on the tetracycline regulatory system, we established a binary transgenic model in which the conditional expression of two transgenes, SV40 T antigen (TAg) and lacZ, can be tightly regulated in the liver by administration of tetracycline. The mouse albumin or mouse major urinary protein promoter was used to achieve liver-specific expression of the tetracycline-responsive transcriptional activator (tTA) in one set of transgenic mice. These mice were crossed with transgenic mice carrying either TAg or lacZ under the control of the tTA-regulated promoter. Analyses of mice transgenic for both tTA and TAg (or lacZ) revealed that the liver-specific expression of the transgenes could be suppressed to undetectable levels and regulated in a reversible fashion by tetracycline administration and withdrawal. Mice with tTA and TAg transgenes developed hepatocellular adenomas and hyperplasia that could be prevented by continuous tetracycline administration. Our report demonstrates the value of this binary transgenic model in studying the physiological functions of any potential genes of interest in a liver-specific manner. JF - The Journal of biological chemistry AU - Manickan, E AU - Satoi, J AU - Wang, T C AU - Liang, T J AD - Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/04/27/ PY - 2001 DA - 2001 Apr 27 SP - 13989 EP - 13994 VL - 276 IS - 17 SN - 0021-9258, 0021-9258 KW - Albumins KW - 0 KW - Anti-Bacterial Agents KW - Antigens, Polyomavirus Transforming KW - Proteins KW - major urinary proteins KW - Tetracycline KW - F8VB5M810T KW - Index Medicus KW - Animals KW - Gene Transfer Techniques KW - Spleen -- metabolism KW - Albumins -- genetics KW - Anti-Bacterial Agents -- pharmacology KW - Mice KW - Adenoma -- virology KW - Transgenes -- genetics KW - Mice, Transgenic KW - Proteins -- genetics KW - Transcriptional Activation KW - Genotype KW - Promoter Regions, Genetic KW - Hyperplasia -- genetics KW - Crosses, Genetic KW - Gene Expression Regulation KW - Hyperplasia -- virology KW - Tetracycline -- pharmacology KW - Adenoma -- genetics KW - Lac Operon KW - Liver Neoplasms -- pathology KW - Antigens, Polyomavirus Transforming -- biosynthesis KW - Liver Neoplasms -- virology KW - Liver -- metabolism KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70788053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Conditional+liver-specific+expression+of+simian+virus+40+T+antigen+leads+to+regulatable+development+of+hepatic+neoplasm+in+transgenic+mice.&rft.au=Manickan%2C+E%3BSatoi%2C+J%3BWang%2C+T+C%3BLiang%2C+T+J&rft.aulast=Manickan&rft.aufirst=E&rft.date=2001-04-27&rft.volume=276&rft.issue=17&rft.spage=13989&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-04-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Biol Chem 2002 Jan 4;277(1):869 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children AN - 17859612; 5111419 AB - Typhoid fever is common in developing countries. The licensed typhoid vaccines confer only about 70 percent immunity, do not protect young children, and are not used for routine vaccination. A newly devised conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old. In a double-blind, randomized trial, we evaluated the safety, immunogenicity, and efficacy of the Vi-rEPA vaccine in children two to five years old in 16 communes in Dong Thap Province, Vietnam. Each of the 11,091 children received two injections six weeks apart of either Vi-rEPA or a saline placebo. Cases of typhoid, diagnosed by the isolation of S. typhi from blood cultures after 3 or more days of fever (a temperature of 37.5 degree C or higher), were identified by active surveillance over a period of 27 months. We estimated efficacy by comparing the attack rate of typhoid in the vaccine group with that in the placebo group. S. typhi was isolated from 4 of the 5525 children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children who received both injections of placebo (efficacy, 91.5 percent; 95 percent confidence interval, 77.1 to 96.6 percent; P<0.001). Among the 771 children who received only one injection, there was 1 case of typhoid in the vaccine group and 8 cases in the placebo group. Cases were distributed evenly among all age groups and throughout the study period. No serious adverse reactions were observed. In all 36 children studied four weeks after the second injection of the vaccine, levels of serum IgG Vi antibodies had increased by a factor of 10 or more. The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than 90 percent efficacy in children two to five years old. The antibody responses and the efficacy suggest that this vaccine should be at least as protective in persons who are more than five years old. JF - New England Journal of Medicine AU - Lin, FYC AU - Ho, V A AU - Khiem, H B AU - Trach, D D AU - Van Bay, P AU - Thanh, T C AU - Kossaczka, Z AU - Bryla, DA AU - Shiloach, J AU - Robbins, J B AU - Schneerson, R AU - Szu, S C AD - National Institute of Child Health and Human Development, Rm. 7B03, 6100 Executive Blvd., Bethesda, MD 20892-7510, USA, link@exchange.nih.gov Y1 - 2001/04/26/ PY - 2001 DA - 2001 Apr 26 SP - 1263 EP - 1269 VL - 344 IS - 17 SN - 0028-4793, 0028-4793 KW - man KW - Salmonella typhi KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Vaccines KW - Children KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17859612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+England+Journal+of+Medicine&rft.atitle=The+efficacy+of+a+Salmonella+typhi+Vi+conjugate+vaccine+in+two-to-five-year-old+children&rft.au=Lin%2C+FYC%3BHo%2C+V+A%3BKhiem%2C+H+B%3BTrach%2C+D+D%3BVan+Bay%2C+P%3BThanh%2C+T+C%3BKossaczka%2C+Z%3BBryla%2C+DA%3BShiloach%2C+J%3BRobbins%2C+J+B%3BSchneerson%2C+R%3BSzu%2C+S+C&rft.aulast=Lin&rft.aufirst=FYC&rft.date=2001-04-26&rft.volume=344&rft.issue=17&rft.spage=1263&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhi; Vaccines; Children ER - TY - JOUR T1 - Bullying Behaviors Among US Youth Prevalence and Association With Psychosocial Adjustment AN - 18377039; 5356503 AB - Although violence among US youth is a current major concern, bullying is infrequently addressed and no national data on the prevalence of bullying are available. To measure the prevalence of bullying behaviors among US youth and to determine the association of bullying and being bullied with indicators of psychosocial adjustment, including problem behavior, school adjustment, social/emotional adjustment, and parenting. Analysis of data from a representative sample of 15 686 students in grades 6 through 10 in public and private schools throughout the United States who completed the World Health Organization's Health Behaviour in School-aged Children survey during the spring of 1998. Self-report of involvement in bullying and being bullied by others. A total of 29.9% of the sample reported moderate or frequent involvement in bullying, as a bully (13.0%), one who was bullied (10.6%), or both (6.3%). Males were more likely than females to be both perpetrators and targets of bullying. The frequency of bullying was higher among 6th- through 8th-grade students than among 9th- and 10th-grade students. Perpetrating and experiencing bullying were associated with poorer psychosocial adjustment (P<.001); however, different patterns of association occurred among bullies, those bullied, and those who both bullied others and were bullied themselves. The prevalence of bullying among US youth is substantial. Given the concurrent behavioral and emotional difficulties associated with bullying, as well as the potential long-term negative outcomes for these youth, the issue of bullying merits serious attention, both for future research and preventive intervention. JF - Journal of the American Medical Association AU - Nansel, T R AU - Overpeck, M AU - Pilla, R S AU - Ruan, W J AU - Simons-Morton, B AU - Scheidt, P AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, 6100 Executive Blvd, Room 7B05, MSC 7510, Bethesda, MD 20892-7510, USA, nanselt@mail.nih.gov Y1 - 2001/04/25/ PY - 2001 DA - 2001 Apr 25 SP - 2094 EP - 2100 VL - 285 IS - 16 SN - 0098-7484, 0098-7484 KW - aggressive behavior KW - bullying KW - Risk Abstracts KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18377039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Medical+Association&rft.atitle=Bullying+Behaviors+Among+US+Youth+Prevalence+and+Association+With+Psychosocial+Adjustment&rft.au=Nansel%2C+T+R%3BOverpeck%2C+M%3BPilla%2C+R+S%3BRuan%2C+W+J%3BSimons-Morton%2C+B%3BScheidt%2C+P&rft.aulast=Nansel&rft.aufirst=T&rft.date=2001-04-25&rft.volume=285&rft.issue=16&rft.spage=2094&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. AN - 70812829; 11320258 AB - Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sora, I AU - Hall, F S AU - Andrews, A M AU - Itokawa, M AU - Li, X F AU - Wei, H B AU - Wichems, C AU - Lesch, K P AU - Murphy, D L AU - Uhl, G R AD - Molecular Neurobiology, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2001/04/24/ PY - 2001 DA - 2001 Apr 24 SP - 5300 EP - 5305 VL - 98 IS - 9 SN - 0027-8424, 0027-8424 KW - Biogenic Monoamines KW - 0 KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Receptor, Serotonin, 5-HT1B KW - Receptors, Serotonin KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a3 protein, mouse KW - Slc6a4 protein, mouse KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Motor Activity -- physiology KW - Brain -- metabolism KW - Mice KW - Receptors, Serotonin -- metabolism KW - Biogenic Monoamines -- metabolism KW - Conditioning (Psychology) -- drug effects KW - Mice, Knockout KW - Body Weight KW - Genotype KW - Conditioning (Psychology) -- physiology KW - Cocaine-Related Disorders -- physiopathology KW - Motor Activity -- drug effects KW - Cocaine-Related Disorders -- metabolism KW - Carrier Proteins -- metabolism KW - Reward KW - Carrier Proteins -- genetics KW - Cocaine -- pharmacology KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70812829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Molecular+mechanisms+of+cocaine+reward%3A+combined+dopamine+and+serotonin+transporter+knockouts+eliminate+cocaine+place+preference.&rft.au=Sora%2C+I%3BHall%2C+F+S%3BAndrews%2C+A+M%3BItokawa%2C+M%3BLi%2C+X+F%3BWei%2C+H+B%3BWichems%2C+C%3BLesch%2C+K+P%3BMurphy%2C+D+L%3BUhl%2C+G+R&rft.aulast=Sora&rft.aufirst=I&rft.date=2001-04-24&rft.volume=98&rft.issue=9&rft.spage=5300&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Pharmacol. 1995 Dec 29;294(2-3):531-40 [8750715] Brain Res. 1999 Sep 25;842(2):445-51 [10526141] Psychopharmacology (Berl). 1996 Nov;128(2):150-60 [8956376] Nat Neurosci. 2000 May;3(5):465-71 [10769386] Eur Psychiatry. 2000 Mar;15(2):79-89 [10881203] Psychopharmacol Bull. 1974 Jul;10(3):46-7 [4419439] Pharmacol Biochem Behav. 1977 Aug;7(2):177-80 [144276] Brain Res. 1978 Oct 27;155(2):277-95 [688018] NIDA Res Monogr. 1982 Apr;41:208-14 [6811910] Pharmacol Biochem Behav. 1982 Nov;17(5):901-4 [6817350] Pharmacol Biochem Behav. 1977 Jun;6(6):615-20 [122445] Mol Pharmacol. 1984 Jul;26(1):35-44 [6087116] Psychopharmacology (Berl). 1984;84(2):167-73 [6438676] J Pharmacol Exp Ther. 1987 Sep;242(3):777-83 [3656112] J Neurochem. 1988 Jun;50(6):1783-90 [2967349] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8 [2899326] Pharmacol Biochem Behav. 1988 Aug;30(4):853-8 [3147460] J Pharmacol Exp Ther. 1989 Oct;251(1):142-9 [2795456] Pharmacol Biochem Behav. 1989 Jul;33(3):725-7 [2587615] Eur J Pharmacol. 1989 Dec 7;173(2-3):177-82 [2576228] Life Sci. 1990;46(9):635-45 [2308472] Psychopharmacology (Berl). 1991;103(1):99-102 [1826060] Eur J Pharmacol. 1990 Aug 10;184(2-3):329-32 [2079102] Eur J Pharmacol. 1990 Nov 27;191(2):239-43 [2086242] Trends Neurosci. 1991 Jul;14(7):299-302 [1719677] Trends Pharmacol Sci. 1992 May;13(5):193-200 [1604712] J Neurochem. 1993 Mar;60(3):1167-70 [8094744] Trends Pharmacol Sci. 1992 Dec;13(12):421-5 [1293865] Synapse. 1993 Sep;15(1):58-62 [8310426] Life Sci. 1995;56(7):475-83 [7869827] Pharmacol Biochem Behav. 1995 Aug;51(4):687-92 [7675844] Pharmacol Biochem Behav. 1995 Sep;52(1):65-71 [7501680] Nature. 1996 Feb 15;379(6566):606-12 [8628395] Neuron. 1997 Jul;19(1):127-38 [9247269] Nature. 1997 Aug 7;388(6642):586-9 [9252189] Adv Pharmacol. 1998;42:991-5 [9328064] Mol Pharmacol. 1998 Apr;53(4):649-55 [9547354] Nature. 1998 May 14;393(6681):175-8 [9603521] Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7699-704 [9636213] Alcohol. 1998 Oct;16(3):249-70 [9744857] Brain Res. 1998 Nov 23;812(1-2):279-82 [9813368] J Neurosci. 1998 Dec 1;18(23):10078-89 [9822762] Prog Neurobiol. 1998 Dec;56(6):613-72 [9871940] Psychopharmacology (Berl). 1999 Jan;141(3):242-50 [10027505] Psychopharmacology (Berl). 1999 Feb;142(2):165-74 [10102769] Nat Neurosci. 1998 Jun;1(2):132-7 [10195128] Nat Neurosci. 1998 Nov;1(7):610-5 [10196569] Synapse. 1999 May;32(2):132-5 [10231132] Mol Pharmacol. 1999 Aug;56(2):434-47 [10419565] Psychopharmacology (Berl). 1999 Jun;144(4):389-97 [10435412] J Neurochem. 1999 Sep;73(3):1033-42 [10461892] J Neurosci. 1999 Sep 1;19(17):7648-52 [10460270] Psychopharmacology (Berl). 1999 Sep 1;146(1):60-6 [10485965] Curr Biol. 1996 Aug 1;6(8):935-6 [8805320] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells. AN - 70801121; 11320259 AB - Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of phenacetin), caffeine, and other related drugs individually and in combination on mouse inner medullary collecting duct cells (mIMCD3). The number of rapidly proliferating cells was reduced by approximately 50% by 0.5 mM ASA, salicylic acid, or APAF. The drugs had less effect on confluent cells, which proliferate slowly. Thus, the slow in vivo turnover of IMCD cells could explain why clinical toxicity requires very high doses of these drugs over a very long period. Caffeine greatly potentiated the effect of acetaminophen, pointing to a potential danger of the mixture. Cyclooxygenase (COX) inhibitors, indomethacin and NS-398, did not reduce cell number except at concentrations greatly in excess of those that inhibit COX. Therefore, COX inhibition alone is not toxic. APAF arrests most cells in late G(1) and S and produces a mixed form of cell death with both oncosis (swollen cells and nuclei) and apoptosis. APAF is known to inhibit the synthesis of DNA and cause chromosomal aberrations due to inhibition of ribonucleotide reductase. Such effects of APAF might account for renal medullary cell death in vivo and development of uroepithelial tumors from surviving cells that have chromosomal aberrations. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rocha, G M AU - Michea, L F AU - Peters, E M AU - Kirby, M AU - Xu, Y AU - Ferguson, D R AU - Burg, M B AD - Laboratory of Kidney and Electrolytes Metabolism, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. Y1 - 2001/04/24/ PY - 2001 DA - 2001 Apr 24 SP - 5317 EP - 5322 VL - 98 IS - 9 SN - 0027-8424, 0027-8424 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase Inhibitors KW - Acetaminophen KW - 362O9ITL9D KW - Caffeine KW - 3G6A5W338E KW - Salicylic Acid KW - O414PZ4LPZ KW - Aspirin KW - R16CO5Y76E KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Aspirin -- toxicity KW - Cyclooxygenase Inhibitors -- toxicity KW - Cell Division -- drug effects KW - Salicylic Acid -- toxicity KW - Mice KW - Caffeine -- toxicity KW - Flow Cytometry KW - Microscopy, Electron KW - Indomethacin -- toxicity KW - Acetaminophen -- toxicity KW - Cell Line KW - Kidney Tubules, Collecting -- cytology KW - Kidney Tubules, Collecting -- drug effects KW - Apoptosis -- drug effects KW - Anti-Inflammatory Agents, Non-Steroidal -- toxicity KW - Kidney Tubules, Collecting -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70801121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Direct+toxicity+of+nonsteroidal+antiinflammatory+drugs+for+renal+medullary+cells.&rft.au=Rocha%2C+G+M%3BMichea%2C+L+F%3BPeters%2C+E+M%3BKirby%2C+M%3BXu%2C+Y%3BFerguson%2C+D+R%3BBurg%2C+M+B&rft.aulast=Rocha&rft.aufirst=G&rft.date=2001-04-24&rft.volume=98&rft.issue=9&rft.spage=5317&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Physiol Renal Physiol. 2000 Feb;278(2):F209-18 [10662725] Toxicol Pathol. 1999 Jul-Aug;27(4):484-90 [10485836] Annu Rev Med. 2000;51:511-23 [10774479] Kidney Int. 2000 Dec;58(6):2259-64 [11115060] Nat New Biol. 1972 Jul 26;238(82):104-6 [4505422] Acta Pharmacol Toxicol (Copenh). 1973;32(6):417-29 [4800749] CRC Crit Rev Toxicol. 1976 Oct;4(4):331-52 [791579] Kidney Int. 1978 Jan;13(1):15-26 [101707] Kidney Int. 1980 Nov;18(5):553-61 [7007712] JAMA. 1984 Jun 15;251(23):3123-5 [6726985] J Immunol Methods. 1986 May 22;89(2):271-7 [3486233] Am J Nephrol. 1989;9(5):403-12 [2801788] Mutagenesis. 1990 Sep;5(5):475-80 [2175832] Ann Intern Med. 1991 Aug 1;115(3):165-72 [2058870] Am J Physiol. 1993 Sep;265(3 Pt 2):F416-24 [8214101] Am J Pathol. 1995 Jan;146(1):3-15 [7856735] Mutat Res. 1995 Apr;342(3-4):157-70 [7715617] Cancer Metastasis Rev. 1995 Mar;14(1):17-29 [7606817] Semin Nephrol. 1995 May;15(3):205-13 [7631047] Curr Opin Nephrol Hypertens. 1996 May;5(3):236-41 [8737859] Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):681-6 [9435252] Kidney Int. 1998 Sep;54(3):679-86 [9734593] J Biol Chem. 1999 Apr 9;274(15):10349-55 [10187823] J Biol Chem. 2000 Apr 7;275(14):10342-8 [10744722] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 3'-->5' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability. AN - 70792667; 11309502 AB - Many DNA polymerases (Pol) have an intrinsic 3'-->5' exonuclease (Exo) activity which corrects polymerase errors and prevents mutations. We describe a role of the 3'-->5' Exo of Pol delta as a supplement or backup for the Rad27/Fen1 5' flap endonuclease. A yeast rad27 null allele was lethal in combination with Pol delta mutations in Exo I, Exo II, and Exo III motifs that inactivate its exonuclease, but it was viable with mutations in other parts of Pol delta. The rad27-p allele, which has little phenotypic effect by itself, was also lethal in combination with mutations in the Pol delta Exo I and Exo II motifs. However, rad27-p Pol delta Exo III double mutants were viable. They exhibited strong synergistic increases in CAN1 duplication mutations, intrachromosomal and interchromosomal recombination, and required the wild-type double-strand break repair genes RAD50, RAD51, and RAD52 for viability. Observed effects were similar to those of the rad27-null mutant deficient in the removal of 5' flaps in the lagging strand. These results suggest that the 3'-->5' Exo activity of Pol delta is redundant with Rad27/Fen1 for creating ligatable nicks between adjacent Okazaki fragments, possibly by reducing the amount of strand-displacement in the lagging strand. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jin, Y H AU - Obert, R AU - Burgers, P M AU - Kunkel, T A AU - Resnick, M A AU - Gordenin, D A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2001/04/24/ PY - 2001 DA - 2001 Apr 24 SP - 5122 EP - 5127 VL - 98 IS - 9 SN - 0027-8424, 0027-8424 KW - Amino Acid Transport Systems KW - 0 KW - CAN1 protein, Candida albicans KW - Fungal Proteins KW - Membrane Transport Proteins KW - Multienzyme Complexes KW - Saccharomyces cerevisiae Proteins KW - DNA Polymerase III KW - EC 2.7.7.- KW - Endodeoxyribonucleases KW - EC 3.1.- KW - Exodeoxyribonucleases KW - Flap Endonucleases KW - exodeoxyribonuclease III KW - EC 3.1.11.2 KW - RAD27 protein, S cerevisiae KW - EC 3.1.11.5 KW - Index Medicus KW - Multienzyme Complexes -- metabolism KW - Gene Duplication KW - Multienzyme Complexes -- deficiency KW - Genes, Lethal -- genetics KW - Genome, Fungal KW - Multienzyme Complexes -- genetics KW - Gene Deletion KW - Chromosomes, Fungal -- genetics KW - DNA Repair -- genetics KW - Alleles KW - Recombination, Genetic -- genetics KW - Kinetics KW - Genetic Complementation Test KW - Membrane Transport Proteins -- genetics KW - Saccharomyces cerevisiae -- growth & development KW - Endodeoxyribonucleases -- genetics KW - Endodeoxyribonucleases -- metabolism KW - Saccharomyces cerevisiae -- enzymology KW - Exodeoxyribonucleases -- genetics KW - Mutagenesis -- genetics KW - Exodeoxyribonucleases -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - DNA Replication -- genetics KW - Endodeoxyribonucleases -- deficiency KW - DNA Polymerase III -- genetics KW - Exodeoxyribonucleases -- deficiency KW - DNA Polymerase III -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70792667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+3%27--%26gt%3B5%27+exonuclease+of+DNA+polymerase+delta+can+substitute+for+the+5%27+flap+endonuclease+Rad27%2FFen1+in+processing+Okazaki+fragments+and+preventing+genome+instability.&rft.au=Jin%2C+Y+H%3BObert%2C+R%3BBurgers%2C+P+M%3BKunkel%2C+T+A%3BResnick%2C+M+A%3BGordenin%2C+D+A&rft.aulast=Jin&rft.aufirst=Y&rft.date=2001-04-24&rft.volume=98&rft.issue=9&rft.spage=5122&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods. 1999 Jul;18(3):349-55 [10454996] Annu Rev Biochem. 1998;67:721-51 [9759502] J Theor Biol. 1978 Apr 6;71(3):339-46 [642534] Cell. 1999 Oct 15;99(2):155-66 [10535734] Mol Cell Biol. 1999 Dec;19(12):8361-71 [10567561] Genes Dev. 2000 Jan 1;14(1):1-10 [10640269] J Biol Chem. 2000 Apr 7;275(14):10498-505 [10744741] Biochim Biophys Acta. 2000 Apr 17;1496(2-3):333-40 [10771101] Plant Mol Biol. 2000 Feb;42(3):415-27 [10798612] Mutat Res. 2000 Jun 30;451(1-2):257-75 [10915877] Annu Rev Biochem. 2000;69:497-529 [10966467] J Biol Chem. 2000 Oct 6;275(40):31528-35 [10924513] Mol Cell. 2000 Sep;6(3):593-603 [11030339] J Biol Chem. 2000 Dec 1;275(48):38022-31 [10984490] Mol Cell. 2000 Oct;6(4):803-14 [11090619] J Biol Chem. 2001 Feb 16;276(7):4901-8 [11053418] Mol Gen Genet. 1976 Jan 16;143(2):119-29 [765749] J Biol Chem. 1983 Sep 25;258(18):11165-73 [6411726] J Biol Chem. 1983 Sep 25;258(18):11174-84 [6309835] Cell. 1990 May 4;61(3):419-36 [2185891] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2417-21 [2006180] EMBO J. 1991 Aug;10(8):2165-70 [1648480] Gene. 1992 Mar 1;112(1):139-44 [1551594] Cell. 1992 May 1;69(3):457-70 [1581961] EMBO J. 1993 Apr;12(4):1467-73 [8385605] Annu Rev Biochem. 1993;62:685-713 [7688945] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] Mol Gen Genet. 1995 Jan 20;246(2):212-22 [7862092] Yeast. 1994 Dec;10(13):1793-808 [7747518] Mol Cell Biol. 1995 Aug;15(8):4291-302 [7623823] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Methods Enzymol. 1995;262:49-62 [8594373] Methods Enzymol. 1995;262:363-85 [8594362] Nucleic Acids Res. 1998 Dec 15;26(24):5589-95 [9837987] Mol Cell Biol. 1999 Mar;19(3):2000-7 [10022887] Mol Cell Biol. 1999 Apr;19(4):3177-83 [10082584] Genetics. 1999 May;152(1):47-59 [10224242] J Biol Chem. 1999 Jun 18;274(25):17395-8 [10364165] J Biol Chem. 1999 Jun 18;274(25):17893-900 [10364235] Mol Cell Biol. 1999 Aug;19(8):5373-82 [10409728] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2856-61 [8610131] Cell. 1997 Jan 24;88(2):253-63 [9008166] J Biol Chem. 1997 Feb 21;272(8):4647-50 [9081985] Mol Gen Genet. 1997 Mar 18;254(1):93-7 [9108295] Biol Chem. 1997 May;378(5):345-62 [9191022] Genetics. 1997 Aug;146(4):1239-51 [9258670] Mol Cell Biol. 1998 Apr;18(4):1891-902 [9528760] Mol Cell Biol. 1998 May;18(5):2779-88 [9566897] Genetics. 1998 Apr;148(4):1475-82 [9560367] Genetics. 1998 Apr;148(4):1507-24 [9560370] Genetics. 1998 Apr;148(4):1551-7 [9560374] J Biol Chem. 1998 Jul 31;273(31):19756-62 [9677406] J Biol Chem. 1999 Sep 24;274(39):27481-90 [10488082] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasia. AN - 70792527; 11309512 AB - DNA methylation of tumor suppressor genes is a common feature of human cancer. The cyclin-dependent kinase inhibitor gene p16/Ink4A is hypermethylated in a wide range of malignant tissues and the p14/ARF gene located 20 kb upstream on chromosome 9p21 is also methylated in carcinomas. p14/ARF (ARF, alternative reading frame) does not inhibit the activities of cyclins or cyclin-dependent kinase complexes; however, the importance of the two gene products in the etiology of cancer resides in their involvement in two major cell cycle regulatory pathways: p53 and the retinoblastoma protein, Rb, respectively. Distinct first exons driven from separate promoters are spliced onto the common exons 2 and 3 and the resulting proteins are translated in different reading frames. Both genes are expressed in normal cells but can be alternatively or coordinately silenced when their CpG islands are hypermethylated. Herein, we examined the presence of methyl-CpG binding proteins associated with aberrantly methylated promoters, the distribution of acetylated histones H3 and H4 by chromatin immunoprecipitation assays, and the effect of chemical treatment with 5-aza-2'-deoxycytidine (5aza-dC) and trichostatin A on gene induction in colon cell lines by quantitative reverse transcriptase-PCR. We observed that the methyl-CpG binding protein MBD2 is targeted to methylated regulatory regions and excludes the acetylated histones H3 and H4, resulting in a localized inactive chromatin configuration. When methylated, the genes can be induced by 5aza-dC but the combined action of 5aza-dC and trichostatin A results in robust gene expression. Thus, methyl-CpG binding proteins and histone deacetylases appear to cooperate in vivo, with a dominant effect of DNA methylation toward histone acetylation, and repress expression of tumor suppressor genes hypermethylated in cancers. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Magdinier, F AU - Wolffe, A P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, MD 20892, USA. FrederiqueM@intra.niddk.nih.gov Y1 - 2001/04/24/ PY - 2001 DA - 2001 Apr 24 SP - 4990 EP - 4995 VL - 98 IS - 9 SN - 0027-8424, 0027-8424 KW - Antimetabolites, Antineoplastic KW - 0 KW - Chromatin KW - Cross-Linking Reagents KW - DNA-Binding Proteins KW - Histone Deacetylase Inhibitors KW - Histones KW - Hydroxamic Acids KW - MBD2 protein KW - Proteins KW - RNA, Messenger KW - Tumor Suppressor Protein p14ARF KW - Formaldehyde KW - 1HG84L3525 KW - trichostatin A KW - 3X2S926L3Z KW - 5-aza-2'-deoxycytidine-5'-monophosphate KW - 66642-55-5 KW - DNA KW - 9007-49-2 KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Azacitidine -- pharmacology KW - Acetylation -- drug effects KW - Chromatin -- metabolism KW - Azacitidine -- analogs & derivatives KW - Humans KW - Cross-Linking Reagents -- metabolism KW - RNA, Messenger -- genetics KW - Antimetabolites, Antineoplastic -- pharmacology KW - Tumor Cells, Cultured KW - Histone Deacetylases -- metabolism KW - Promoter Regions, Genetic -- genetics KW - Hydroxamic Acids -- pharmacology KW - DNA -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Protein Binding KW - Transcriptional Activation KW - Chromatin -- genetics KW - RNA, Messenger -- metabolism KW - Formaldehyde -- metabolism KW - Histones -- metabolism KW - Models, Genetic KW - DNA -- genetics KW - Chromatin -- drug effects KW - Substrate Specificity KW - Histones -- genetics KW - Genes, p16 -- genetics KW - Colonic Neoplasms -- genetics KW - DNA Methylation -- drug effects KW - CpG Islands -- genetics KW - Proteins -- genetics KW - Gene Silencing -- drug effects KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70792527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Selective+association+of+the+methyl-CpG+binding+protein+MBD2+with+the+silent+p14%2Fp16+locus+in+human+neoplasia.&rft.au=Magdinier%2C+F%3BWolffe%2C+A+P&rft.aulast=Magdinier&rft.aufirst=F&rft.date=2001-04-24&rft.volume=98&rft.issue=9&rft.spage=4990&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Blood. 1998 Feb 1;91(3):1016-20 [9446664] FASEB J. 2000 Aug;14(11):1585-94 [10928993] Cancer Res. 1998 Mar 15;58(6):1245-52 [9515812] Mol Cell Biol. 1998 Apr;18(4):1793-801 [9528751] Nat Genet. 1998 Jun;19(2):187-91 [9620779] Nature. 1998 May 28;393(6683):386-9 [9620804] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5 [9618505] Mol Cell Biol. 1998 Nov;18(11):6457-73 [9774662] Mol Cell Biol. 1998 Nov;18(11):6538-47 [9774669] Biochim Biophys Acta. 1998 Oct 14;1378(2):F115-77 [9823374] Oncogene. 1998 Dec 17;17(24):3169-76 [9872332] Nat Genet. 1999 Jan;21(1):103-7 [9916800] Trends Genet. 1999 Jan;15(1):34-7 [10087932] Nat Genet. 1999 May;22(1):98-101 [10319871] Genes Dev. 1999 Aug 1;13(15):1924-35 [10444591] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12754-9 [10535995] Cell. 1999 Nov 24;99(5):451-4 [10589672] Nat Genet. 2000 Jan;24(1):88-91 [10615135] Cancer Res. 2000 Jan 1;60(1):129-33 [10646864] Oncogene. 2000 Feb 17;19(7):943-52 [10702803] Mol Cell Biol. 2000 Jul;20(14):5107-18 [10866667] Nat Genet. 2000 Jul;25(3):269-77 [10888872] Nat Genet. 2000 Jul;25(3):338-42 [10888886] Nature. 1986 May 15-21;321(6067):209-13 [2423876] J Mol Biol. 1987 Jul 20;196(2):261-82 [3656447] Cell. 1989 Aug 11;58(3):499-507 [2758464] Cell. 1992 Jun 12;69(6):905-14 [1606614] Curr Opin Genet Dev. 1993 Apr;3(2):226-31 [8504247] Nature. 1994 Apr 21;368(6473):753-6 [8152487] Science. 1994 Apr 15;264(5157):436-40 [8153634] Lab Invest. 1994 Aug;71(2):188-92 [8078298] Cell. 1995 May 5;81(3):323-30 [7736585] Cancer Res. 1995 Jul 15;55(14):2988-94 [7606716] Oncogene. 1995 Jul 6;11(1):21-9 [7624129] Science. 1996 Dec 6;274(5293):1672-7 [8939849] Cell. 1997 Feb 21;88(4):471-81 [9038338] Trends Genet. 1997 Aug;13(8):335-40 [9260521] Adv Cancer Res. 1998;72:141-96 [9338076] Nat Genet. 1999 Sep;23(1):58-61 [10471499] Nat Genet. 1999 Sep;23(1):62-6 [10471500] Science. 1999 Oct 15;286(5439):481-6 [10521337] Cancer Res. 1998 Feb 15;58(4):591-3 [9485004] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signal-binding specificity of the mu4 subunit of the adaptor protein complex AP-4. AN - 77054383; 11139587 AB - The medium (mu) chains of the adaptor protein (AP) complexes AP-1, AP-2, and AP-3 recognize distinct subsets of tyrosine-based (YXXphi) sorting signals found within the cytoplasmic domains of integral membrane proteins. Here, we describe the signal-binding specificity and affinity of the medium subunit mu4 of the recently described adaptor protein complex AP-4. To elucidate the determinants of specificity, we screened a two-hybrid combinatorial peptide library using mu4 as a selector protein. Statistical analyses of the results revealed that mu4 prefers aspartic acid at position Y+1, proline or arginine at Y+2, and phenylalanine at Y-1 and Y+3 (phi). In addition, we examined the interaction of mu4 with naturally occurring YXXphi signals by both two-hybrid and in vitro binding analyses. These experiments showed that mu4 recognized the tyrosine signal from the human lysosomal protein LAMP-2, HTGYEQF. Using surface plasmon resonance measurements, we determined the apparent dissociation constant for the mu4-YXXphi interaction to be in the micromolar range. To gain insight into a possible role of AP-4 in intracellular trafficking, we constructed a Tac chimera bearing a mu4-specific YXXphi signal. This chimera was targeted to the endosomal-lysosomal system without being internalized from the plasma membrane. JF - The Journal of biological chemistry AU - Aguilar, R C AU - Boehm, M AU - Gorshkova, I AU - Crouch, R J AU - Tomita, K AU - Saito, T AU - Ohno, H AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch and the Laboratory of Molecular Genetics, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/04/20/ PY - 2001 DA - 2001 Apr 20 SP - 13145 EP - 13152 VL - 276 IS - 16 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Vesicular Transport KW - 0 KW - Antigens, CD KW - Lysosome-Associated Membrane Glycoproteins KW - Membrane Glycoproteins KW - Monomeric Clathrin Assembly Proteins KW - Nerve Tissue Proteins KW - Peptide Library KW - Phosphoproteins KW - Protein Subunits KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - clathrin assembly protein AP180 KW - Index Medicus KW - Humans KW - Lysosomes -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Signal Transduction KW - Membrane Glycoproteins -- chemistry KW - Recombinant Fusion Proteins -- analysis KW - HeLa Cells KW - Amino Acid Sequence KW - Cloning, Molecular KW - Binding Sites KW - Saccharomyces cerevisiae KW - Transfection KW - Antigens, CD -- chemistry KW - Antigens, CD -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Phosphoproteins -- genetics KW - Phosphoproteins -- chemistry KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77054383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Signal-binding+specificity+of+the+mu4+subunit+of+the+adaptor+protein+complex+AP-4.&rft.au=Aguilar%2C+R+C%3BBoehm%2C+M%3BGorshkova%2C+I%3BCrouch%2C+R+J%3BTomita%2C+K%3BSaito%2C+T%3BOhno%2C+H%3BBonifacino%2C+J+S&rft.aulast=Aguilar&rft.aufirst=R&rft.date=2001-04-20&rft.volume=276&rft.issue=16&rft.spage=13145&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Role of the Synaptic Protein SNAP-25 in the Potency of Botulinum Neurotoxin Type A AN - 17836159; 4871194 AB - Botulinum neurotoxin serotype A (BoNT/A) is distinguished from BoNT/E by longer duration of paralysis and greater potency. The proteolytic activity of BoNT/A in cultures of dissociated spinal cord neurons persists beyond 80 days, whereas BoNT/E activity persists for less than 1 day (Keller, J. E., Neale, E. A. Oyler, G., and Adler, M. (1999) FEBS Lett. 456, 137-142). This single quality of toxin activity can account for the differences observed in the duration of muscle block. In the present work we sought to understand the basis for the apparent greater potency of BoNT/A. BoNT/E cleaves a 26-amino acid fragment from the C terminus of the synaptic protein SNAP-25 whereas BoNT/A removes only nine residues creating a 197-amino acid fragment (P197) that is 95% the length of SNAP-25. We show that inhibition of neurotransmitter release by BoNT/E is equivalent to the damage caused to SNAP-25. However, synaptic blockade by BoNT/A is greater than the extent of SNAP- 25 proteolysis. These findings can be explained if P197 produces an inhibitory effect on neurotransmitter release. A mathematical model of the experimentally determined relationship between SNAP-25 damage and blockade of neurotransmission supports this interpretation. Furthermore, neurotransmitter release following complete cleavage of SNAP-25 can be achieved by P197, but with about 5- fold less sensitivity to external Ca super(2+). In this case, vesicular release is restored by increasing intracellular Ca super(2+). These data demonstrate that P197 competes with intact SNAP-25, but is unable to initiate normal synaptic vesicle fusion in physiological concentrations of Ca super(2+). JF - Journal of Biological Chemistry AU - Keller, JE AU - Neale, E A AD - Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, jekeller@codon.nih.gov Y1 - 2001/04/20/ PY - 2001 DA - 2001 Apr 20 SP - 13476 EP - 13482 VL - 276 IS - 16 SN - 0021-9258, 0021-9258 KW - Neurotoxins KW - SNAP-25 protein KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Calcium KW - Botulism KW - Clostridium botulinum KW - Toxins KW - Botulinum toxin KW - Neurotransmitters KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17836159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+Role+of+the+Synaptic+Protein+SNAP-25+in+the+Potency+of+Botulinum+Neurotoxin+Type+A&rft.au=Keller%2C+JE%3BNeale%2C+E+A&rft.aulast=Keller&rft.aufirst=JE&rft.date=2001-04-20&rft.volume=276&rft.issue=16&rft.spage=13476&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium botulinum; Toxins; Neurotransmitters; Calcium; Botulinum toxin; Botulism ER - TY - JOUR T1 - Guidelines 2000 for Colon and Rectal Cancer Surgery AN - 220978803; 11309435 AB - Background: Oncologic resection techniques affect outcome for colon cancer and rectal cancer, but standardized guidelines have not been adopted. The National Cancer Institute sponsored a panel of experts to systematically review current literature and to draft guidelines that provide uniform definitions, principles, and practices. Methods: Methods were similar to those described by the American Society of Clinical Oncology in developing practice guidelines. Experts representing oncology and surgery met to review current literature on oncologic resection techniques for level of evidence (I-V, where I is the best evidence and V is the least compelling) and grade of recommendation (A-D, where A is based on the best evidence and D is based on the weakest evidence). Initial guidelines were drafted, reviewed, and accepted by consensus. Results: For the following seven factors, the level of evidence was II, III, or IV, and the findings were generally consistent (grade B): anatomic definition of colon versus rectum, tumor-node-metastasis staging, radial margins, adjuvant R0 stage, inadvertent rectal perforation, distal and proximal rectal margins, and en bloc resection of adherent tumors. For another seven factors, the level of evidence was II, III, or IV, but findings were inconsistent (grade C): laparoscopic colectomy; colon lymphadenectomy; level of proximal vessel ligation, mesorectal excision, and extended lateral pelvic lymph node dissection (all three for rectal cancer); no-touch technique; and bowel washout. For the other four factors, there was little or no systematic empirical evidence (grade D): abdominal exploration, oophorectomy, extent of colon resection, and total length of rectum resected. Conclusions: The panel reports surgical guidelines and definitions based on the best available evidence. The availability of more standardized information in the future should allow for more grade A recommendations. JF - Journal of the National Cancer Institute AU - Nelson, Heidi AU - Petrelli, Nicholas AU - Carlin, Arthur AU - Couture, Jean AU - Fleshman, James AU - Guillem, Jose AU - Miedema, Brent AU - Ota, David AU - Sargent, Daniel Y1 - 2001/04/18/ PY - 2001 DA - 2001 Apr 18 SP - 583 EP - 96 CY - Oxford PB - Oxford Publishing Limited(England) VL - 93 IS - 8 SN - 00278874 KW - Medical Sciences--Oncology KW - Humans KW - Surgical Procedures, Operative -- standards KW - Rectal Neoplasms -- surgery KW - Colonic Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/220978803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Guidelines+2000+for+Colon+and+Rectal+Cancer+Surgery%3A+p.+640&rft.au=Nelson%2C+Heidi%3BPetrelli%2C+Nicholas%3BCarlin%2C+Arthur%3BCouture%2C+Jean%3BFleshman%2C+James%3BGuillem%2C+Jose%3BMiedema%2C+Brent%3BOta%2C+David%3BSargent%2C+Daniel&rft.aulast=Nelson&rft.aufirst=Heidi&rft.date=2001-04-18&rft.volume=93&rft.issue=8&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright Oxford University Press(England) Apr 18, 2001 N1 - Last updated - 2014-05-22 N1 - CODEN - JNCIEQ ER - TY - JOUR T1 - Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms. AN - 77058229; 11304786 AB - To define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of the novel protein kinase inhibitor, UCN-01 (7-hydroxystaurosporine), administered as a 72-hour continuous intravenous infusion (CIV). Forty-seven patients with refractory neoplasms received UCN-01 during this phase I trial. Total, free plasma, and salivary concentrations were determined; the latter were used to address the influence of plasma protein binding on peripheral tissue distribution. The phosphorylation state of the protein kinase C (PKC) substrate alpha-adducin and the abrogation of DNA damage checkpoint also were assessed. The recommended phase II dose of UCN-01 as a 72-hour CIV is 42.5 mg/m(2)/d for 3 days. Avid plasma protein binding of UCN-01, as measured during the trial, dictated a change in dose escalation and administration schedules. Therefore, nine patients received drug on the initial 2-week schedule, and 38 received drug on the recommended 4-week schedule. DLTs at 53 mg/m(2)/d for 3 days included hyperglycemia with resultant metabolic acidosis, pulmonary dysfunction, nausea, vomiting, and hypotension. Pharmacokinetic determinations at the recommended dose of 42.5 mg/m(2)/d for 3 days included mean total plasma concentration of 36.4 microM (terminal elimination half-life range, 447 to 1176 hours), steady-state volume of distribution of 9.3 to 14.2 L, and clearances of 0.005 to 0.033 L/h. The mean total salivary concentration was 111 nmol/L of UCN-01. One partial response was observed in a patient with melanoma, and one protracted period ( > 2.5 years) of disease stability was observed in a patient with alk-positive anaplastic large-cell lymphoma. Preliminary evidence suggests UCN-01 modulation of both PKC substrate phosphorylation and the DNA damage-related G(2) checkpoint. UCN-01 can be administered safely as an initial 72-hour CIV with subsequent monthly doses administered as 36-hour infusions. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Sausville, E A AU - Arbuck, S G AU - Messmann, R AU - Headlee, D AU - Bauer, K S AU - Lush, R M AU - Murgo, A AU - Figg, W D AU - Lahusen, T AU - Jaken, S AU - Jing , X AU - Roberge, M AU - Fuse, E AU - Kuwabara, T AU - Senderowicz, A M AD - Developmental Therapeutics Program Clinical Trials Unit, Medicine Branch, and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20852, USA. Sausville@nih.gov Y1 - 2001/04/15/ PY - 2001 DA - 2001 Apr 15 SP - 2319 EP - 2333 VL - 19 IS - 8 SN - 0732-183X, 0732-183X KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Hypotension -- chemically induced KW - Drug Administration Schedule KW - Infusions, Intravenous KW - DNA Damage KW - Dose-Response Relationship, Drug KW - Humans KW - Vomiting -- chemically induced KW - Aged KW - Drug Resistance, Neoplasm KW - Staurosporine -- analogs & derivatives KW - Skin Neoplasms -- drug therapy KW - Nausea -- chemically induced KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Hyperglycemia -- chemically induced KW - Melanoma -- drug therapy KW - Adult KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Antineoplastic Agents -- administration & dosage KW - Alkaloids -- adverse effects KW - Antineoplastic Agents -- pharmacokinetics KW - Alkaloids -- pharmacokinetics KW - Antineoplastic Agents -- adverse effects KW - Alkaloids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77058229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+trial+of+72-hour+continuous+infusion+UCN-01+in+patients+with+refractory+neoplasms.&rft.au=Sausville%2C+E+A%3BArbuck%2C+S+G%3BMessmann%2C+R%3BHeadlee%2C+D%3BBauer%2C+K+S%3BLush%2C+R+M%3BMurgo%2C+A%3BFigg%2C+W+D%3BLahusen%2C+T%3BJaken%2C+S%3BJing+%2C+X%3BRoberge%2C+M%3BFuse%2C+E%3BKuwabara%2C+T%3BSenderowicz%2C+A+M&rft.aulast=Sausville&rft.aufirst=E&rft.date=2001-04-15&rft.volume=19&rft.issue=8&rft.spage=2319&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts. AN - 77037192; 11295534 AB - 8-oxo-deoxyguanosine (8-oxodG) is one of the major DNA lesions formed upon oxidative attack of DNA. It is a mutagenic adduct that has been associated with pathological states such as cancer and aging. Base excision repair (BER) is the main pathway for the repair of 8-oxodG. There is a great deal of interest in the question about age-associated accumulation of this DNA lesion and its intracellular distribution, particularly with respect to mitochondrial or nuclear localization. We have previously shown that 8-oxodG-incision activity increases with age in rat mitochondria obtained from both liver and heart. In this study, we have investigated the age-associated changes in DNA repair activities in both mitochondrial and nuclear extracts obtained from mouse liver. We observed that 8-oxodG incision activity of mitochondrial extracts increases significantly with age, from 13.4 + or - 2.2 fmoles of oligomer/100 microg of protein/16 h at 6 to 18.6 + or - 4.9 at 14 and 23.7 + or - 3.8 at 23 months of age. In contrast, the nuclear 8-oxodG incision activity showed no significant change with age, and in fact slightly decreased from 11.8 + or - 3 fmoles/50 microg of protein/2 h at 6 months to 9.7 + or - 0.8 at 14 months. Uracil DNA glycosylase and endonuclease G activities did not change with age in nucleus or mitochondria. Our results show that the repair of 8-oxodG is regulated differently in nucleus and mitochondria during the aging process. The specific increase in 8-oxodG-incision activity in mitochondria, rather than a general up-regulation of DNA metabolizing enzymes in those organelles, suggests that this pathway may be up regulated during aging in mice. JF - Free radical biology & medicine AU - de Souza-Pinto, N C AU - Hogue, B A AU - Bohr, V A AD - Laboratory of Molecular Genetics, NIA, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2001/04/15/ PY - 2001 DA - 2001 Apr 15 SP - 916 EP - 923 VL - 30 IS - 8 SN - 0891-5849, 0891-5849 KW - Cell Extracts KW - 0 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Citrate (si)-Synthase KW - EC 2.3.3.1 KW - Endodeoxyribonucleases KW - EC 3.1.- KW - endonuclease G KW - EC 3.1.21.- KW - DNA Glycosylases KW - EC 3.2.2.- KW - N-Glycosyl Hydrolases KW - Uracil-DNA Glycosidase KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Endodeoxyribonucleases -- metabolism KW - Citrate (si)-Synthase -- metabolism KW - Male KW - Aging -- metabolism KW - Mitochondria, Liver -- enzymology KW - Deoxyguanosine -- metabolism KW - Cell Nucleus -- enzymology KW - DNA Repair KW - N-Glycosyl Hydrolases -- metabolism KW - Cell Nucleus -- metabolism KW - Mitochondria, Liver -- metabolism KW - Mitochondria, Liver -- genetics KW - Cell Nucleus -- genetics KW - Aging -- genetics KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77037192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=DNA+repair+and+aging+in+mouse+liver%3A+8-oxodG+glycosylase+activity+increase+in+mitochondrial+but+not+in+nuclear+extracts.&rft.au=de+Souza-Pinto%2C+N+C%3BHogue%2C+B+A%3BBohr%2C+V+A&rft.aulast=de+Souza-Pinto&rft.aufirst=N&rft.date=2001-04-15&rft.volume=30&rft.issue=8&rft.spage=916&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus. AN - 77033256; 11290600 AB - Kaposi sarcoma-associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in single cells was determined by quantitative flow cytometry. Viral particle production was determined by electron microscope analyses and detection of minor capsid protein in culture supernatants. Agents that mobilized intracellular calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle-associated proteins and led to increased virus production. Calcium-mediated virus reactivation was blocked by specific inhibitors of calcineurin-dependent signal transduction (cyclosporine, FK506). Similarly, calcium-mediated virus reactivation in KSHV-infected dermal microvascular endothelial cells was blocked by cyclosporine. Furthermore, retroviral transduction with plasmid DNA encoding VIVIT, a peptide specifically blocking calcineurin-NFAT interactions, inhibited calcium-dependent KSHV reactivation. By contrast, chemical induction of lytic-phase infection by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate was blocked by protein kinase C inhibitors, but not by calcineurin inhibitors. In summary, calcineurin-dependent signal transduction, an important signaling cascade in vivo, induces calcium-dependent KSHV replication, providing a possible target for the design of antiherpesvirus strategies in KSHV-infected patients. JF - Blood AU - Zoeteweij, J P AU - Moses, A V AU - Rinderknecht, A S AU - Davis, D A AU - Overwijk, W W AU - Yarchoan, R AU - Orenstein, J M AU - Blauvelt, A AD - Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA. Y1 - 2001/04/15/ PY - 2001 DA - 2001 Apr 15 SP - 2374 EP - 2380 VL - 97 IS - 8 SN - 0006-4971, 0006-4971 KW - Calcineurin Inhibitors KW - 0 KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Indoles KW - Maleimides KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Transcription Factors KW - Viral Proteins KW - Ionomycin KW - 56092-81-0 KW - Thapsigargin KW - 67526-95-8 KW - Cyclosporine KW - 83HN0GTJ6D KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcineurin KW - EC 3.1.3.16 KW - Staurosporine KW - H88EPA0A3N KW - bisindolylmaleimide KW - MBK3OO5K8T KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Tacrolimus KW - WM0HAQ4WNM KW - Abridged Index Medicus KW - Index Medicus KW - Calcineurin -- physiology KW - Transcription, Genetic -- drug effects KW - Transcription Factors -- antagonists & inhibitors KW - Humans KW - Viral Proteins -- biosynthesis KW - Ionomycin -- pharmacology KW - Phosphorylation KW - Cyclosporine -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Microscopy, Electron KW - Maleimides -- pharmacology KW - Endothelium, Vascular -- cytology KW - Protein Processing, Post-Translational KW - Thapsigargin -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Staurosporine -- pharmacology KW - Capsid -- analysis KW - Transfection KW - Cells, Cultured KW - Tacrolimus -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Endothelium, Vascular -- virology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Protein Kinase C -- physiology KW - Calcium Signaling -- drug effects KW - Virus Activation -- drug effects KW - Calcium Signaling -- physiology KW - Herpesvirus 8, Human -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77033256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Targeted+inhibition+of+calcineurin+signaling+blocks+calcium-dependent+reactivation+of+Kaposi+sarcoma-associated+herpesvirus.&rft.au=Zoeteweij%2C+J+P%3BMoses%2C+A+V%3BRinderknecht%2C+A+S%3BDavis%2C+D+A%3BOverwijk%2C+W+W%3BYarchoan%2C+R%3BOrenstein%2C+J+M%3BBlauvelt%2C+A&rft.aulast=Zoeteweij&rft.aufirst=J&rft.date=2001-04-15&rft.volume=97&rft.issue=8&rft.spage=2374&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Potency and Durability of DNA- and Protein-Based Vaccines Against Leishmania major Evaluated Using Low-Dose, Intradermal Challenge AN - 17842677; 4869328 AB - DNA- and protein- based vaccines against cutaneous leishmaniasis due to Leishmania major were evaluated using a challenge model that more closely reproduces the pathology and immunity associated with sand fly-transmitted infection. C57BL/6 mice were vaccinated s.c. with a mixture of plasmid DNAs encoding the Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or with autoclaved L. major promastigotes (ALM) plus rIL-12, and the mice were challenged by inoculation of 100 metacyclic promastigotes in the ear dermis. When challenged at 2 wk postvaccination, mice receiving AgDNA or ALM/rIL-12 were completely protected against the development of dermal lesions, and both groups had a 100-fold reduction in peak dermal parasite loads compared with controls. When challenged at 12 wk, mice vaccinated with ALM/rIL-12 maintained partial protection against dermal lesions and their parasite loads were no longer significantly reduced, whereas the mice vaccinated with AgDNA remained completely protected and had a 1000-fold reduction in dermal parasite loads. Mice vaccinated with AgDNA also harbored few, if any, parasites in the skin during the chronic phase, and their ability to transmit L. major to vector sand flies was completely abrogated. The durable protection in mice vaccinated with AgDNA was associated with the recruitment of both CD8 super(+) and CD4 super(+) T cells to the site of intradermal challenge and with IFN- gamma production by CD8 super(+) T cells in lymph nodes draining the challenge site. These data suggest that under conditions of natural challenge, DNA vaccination has the capacity to confer complete protection against cutaneous leishmaniasis and to prevent the establishment of infection reservoirs. JF - Journal of Immunology AU - Mendez, S AU - Gurunathan, S AU - Kamhawi, S AU - Belkaid, Y AU - Moga, MA AU - Skeiky, YAW AU - Campos-Neto, A AU - Reed, S AU - Seder, R A AU - Sacks, D AD - Laboratory of Parasitic Diseases and Laboratory of Clinical Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 Y1 - 2001/04/15/ PY - 2001 DA - 2001 Apr 15 SP - 5122 EP - 5128 VL - 166 IS - 8 SN - 0022-1767, 0022-1767 KW - mice KW - Leishmania major KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - Skin KW - Interleukin 2 KW - Plasmids KW - DNA vaccines KW - Lymphocytes T KW - Vaccines KW - Cutaneous leishmaniasis KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17842677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=The+Potency+and+Durability+of+DNA-+and+Protein-Based+Vaccines+Against+Leishmania+major+Evaluated+Using+Low-Dose%2C+Intradermal+Challenge&rft.au=Mendez%2C+S%3BGurunathan%2C+S%3BKamhawi%2C+S%3BBelkaid%2C+Y%3BMoga%2C+MA%3BSkeiky%2C+YAW%3BCampos-Neto%2C+A%3BReed%2C+S%3BSeder%2C+R+A%3BSacks%2C+D&rft.aulast=Mendez&rft.aufirst=S&rft.date=2001-04-15&rft.volume=166&rft.issue=8&rft.spage=5122&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Leishmania major; Lymphocytes T; Skin; Vaccines; Plasmids; Interleukin 2; Cutaneous leishmaniasis; DNA vaccines ER - TY - JOUR T1 - TRAM, a predicted RNA-binding domain, common to tRNA uracil methylation and adenine thiolation enzymes AN - 17853935; 4881448 AB - A previously undetected conserved domain is identified in two distinct classes of tRNA-modifying enzymes, namely uridine methylases of the TRM2 family and enzymes of the MiaB family that are involved in 2-methylthioadenine formation. This domain, for which the acronym TRAM is proposed after TRM2 and MiaB, is predicted to bind tRNA and deliver the RNA-modifying enzymatic domains to their targets. In addition to the two families of RNA-modifying enzymes, the TRAM domain is present in several other proteins associated with the translation machinery and in a family of small, uncharacterized archaeal proteins that are predicted to have a role in the regulation of tRNA modification or translation. Secondary structure prediction indicates that the TRAM domain adopts a simple beta -barrel fold. In addition, sequence analysis of the MiaB family enzymes showed that they share the predicted catalytic site with biotin and lipoate synthases and probably employ the same mechanism for sulfur insertion into their respective substrate. JF - FEMS Microbiology Letters AU - Anantharaman, V AU - Koonin, E V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 20894 Bethesda, MD USA Y1 - 2001/04/13/ PY - 2001 DA - 2001 Apr 13 SP - 215 EP - 221 PB - Elsevier Science VL - 197 IS - 2 SN - 0378-1097, 0378-1097 KW - TRAM domain KW - 2-methylthioadenine KW - MiaB protein KW - uracil KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - tRNA KW - Secondary structure KW - Methylation KW - J 02726:RNA and ribosomes KW - N 14320:Chemical reactions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17853935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=TRAM%2C+a+predicted+RNA-binding+domain%2C+common+to+tRNA+uracil+methylation+and+adenine+thiolation+enzymes&rft.au=Anantharaman%2C+V%3BKoonin%2C+E+V%3BAravind%2C+L&rft.aulast=Anantharaman&rft.aufirst=V&rft.date=2001-04-13&rft.volume=197&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - tRNA; Methylation; Secondary structure ER - TY - JOUR T1 - Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice. AN - 70851572; 11360188 AB - We have previously demonstrated that amplification and overexpression of the Ki-ras gene is associated with mammary tumor progression in C3(1)/SV40Tag transgenic mice (Liu et al., 1998). To further evaluate the functional significance of the Ki-ras proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-ras gene dosage on tumor progression. The lack of one normal Ki-ras allele C3(1)/SV40Tag transgenic mice resulted in significantly delayed mammary intraepithelial neoplasia (MIN) formation as well as in a decreased number of mammary gland carcinomas. However, despite the retardation of tumor development by reduced Ki-ras gene dosage, overall survival was only modestly affected. This appears to be due to several factors including significant mammary tumor growth associated with Ki-ras gene amplification and over-expression that occurs during the advanced stage of oncogenesis in mice carrying either one or two normal Ki-ras alleles. The retardation of tumor progression due to the haploid loss of Ki-ras did not appear to be related to accelerated apoptosis, or a reduced rate of cell proliferation at the tumor stages examined. These data strongly suggest that the gene dosage of Ki-ras affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis. JF - Oncogene AU - Liu, M L AU - Shibata, M A AU - Von Lintig, F C AU - Wang, W AU - Cassenaer, S AU - Boss, G R AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institute of Health, Bethesda, Maryland, MD 20892, USA. Y1 - 2001/04/12/ PY - 2001 DA - 2001 Apr 12 SP - 2044 EP - 2049 VL - 20 IS - 16 SN - 0950-9232, 0950-9232 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Animals KW - Apoptosis -- genetics KW - Haploidy KW - Disease Progression KW - Mice KW - Mice, Transgenic KW - Male KW - Female KW - Cell Division -- genetics KW - Mice, Knockout KW - Genes, ras -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Antigens, Polyomavirus Transforming -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70851572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Haploid+loss+of+Ki-ras+delays+mammary+tumor+progression+in+C3+%281%29%2FSV40+Tag+transgenic+mice.&rft.au=Liu%2C+M+L%3BShibata%2C+M+A%3BVon+Lintig%2C+F+C%3BWang%2C+W%3BCassenaer%2C+S%3BBoss%2C+G+R%3BGreen%2C+J+E&rft.aulast=Liu&rft.aufirst=M&rft.date=2001-04-12&rft.volume=20&rft.issue=16&rft.spage=2044&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-associated non-Hodgkin lymphoma: incidence, presentation, and prognosis. AN - 77061766; 11308402 AB - Patients with acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin lymphoma often present with multiple poor prognostic features, including significant tumor burden, advanced immunosuppression, and other concurrent morbidities. Strategies to manage such complex multiple-disease cases have often incorporated the assumption that prospects for long-term survival are poor and that intensive therapy cannot be tolerated and so is not justified. Since the advent of highly active antiretroviral therapy for human immunodeficiency virus infection, life expectancy has improved substantially for patients in whom the virus can be successfully suppressed. Thus, for complicated cases involving AIDS-associated malignancy, a reassessment of treatment strategies and the potential for long-term survival is warranted. Here, we present the case of a patient with poor prognosis due to AIDS-associated lymphoma with leptomeningeal involvement, advanced immunosuppression, and deep venous thrombosis. The management of this case illustrates that a multidisciplinary approach to complex AIDS cases involving malignancy and concurrent morbidity can result in a return to functional health in affected patients. Successful strategies for achieving favorable outcomes currently exist with available therapies. JF - JAMA AU - Little, R F AU - Gutierrez, M AU - Jaffe, E S AU - Pau, A AU - Horne, M AU - Wilson, W AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bldg 10, Room 10S255, 9000 Rockville Pike, Bethesda, MD 20892, USA. rlittle@helix.nih.gov Y1 - 2001/04/11/ PY - 2001 DA - 2001 Apr 11 SP - 1880 EP - 1885 VL - 285 IS - 14 SN - 0098-7484, 0098-7484 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Thrombolytic Therapy KW - Cyclophosphamide -- administration & dosage KW - Venous Thrombosis -- complications KW - Humans KW - Vincristine -- administration & dosage KW - Prognosis KW - Doxorubicin -- administration & dosage KW - Biopsy, Needle KW - HIV Infections -- diagnosis KW - Etoposide -- administration & dosage KW - HIV Infections -- drug therapy KW - Antiretroviral Therapy, Highly Active KW - Incidence KW - Middle Aged KW - Flow Cytometry KW - Venous Thrombosis -- drug therapy KW - Immunohistochemistry KW - Immunophenotyping KW - Prednisone -- administration & dosage KW - Male KW - Lymphoma, AIDS-Related -- epidemiology KW - Lymphoma, AIDS-Related -- complications KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- diagnosis KW - Lymphoma, Non-Hodgkin -- complications KW - Lymphoma, AIDS-Related -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Lymphoma, AIDS-Related -- diagnosis KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77061766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=HIV-associated+non-Hodgkin+lymphoma%3A+incidence%2C+presentation%2C+and+prognosis.&rft.au=Little%2C+R+F%3BGutierrez%2C+M%3BJaffe%2C+E+S%3BPau%2C+A%3BHorne%2C+M%3BWilson%2C+W&rft.aulast=Little&rft.aufirst=R&rft.date=2001-04-11&rft.volume=285&rft.issue=14&rft.spage=1880&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Features of the 3'-consensus sequence of rotavirus mRNAs critical to minus strand synthesis. AN - 77031226; 11289804 AB - The last seven nucleotides of the 3'-end of rotavirus mRNAs, 5'-UGUGACC-3', are highly conserved and form a cis-acting signal that can promote the synthesis of (-) strand RNA to produce the viral dsRNA genome in vitro. Previous studies have shown that the sequence, location, and strandedness (single- versus double-stranded) of the 3'-consensus sequence of the mRNA affect the efficiency of (-) strand synthesis. In this study, we have used exhaustive mutagenesis of the SA11 gene 8 mRNA and an in vitro replication system to define the importance of each of the residues in the consensus sequence in (-) strand synthesis. The analysis showed that the CC of the consensus sequence was the most critical for (-) strand synthesis. Furthermore, the data revealed that other, but not all, residues of the consensus sequence contributed to efficient (-) strand synthesis in vitro. Mutant gene 8 RNAs supported an intermediate level of (-) strand synthesis when the 15 nt sequence upstream of the CC was replaced with long tracts of poly(A) or poly(U), but not with poly(G). Predictions of the secondary structure of the mutant RNAs suggested that the poly(G)-RNA could not replicate because its 3'-terminus was largely basepaired, instead of extending as a single-stranded tail as is the case for the 3'-termini of the poly(A)- and poly(U)-RNAs and wild-type gene 8 RNA. Subsequent experiments performed with complementary oligonucleotides indicated that efficient RNA replication occurs in vitro only when the last four residues of the 3'-consensus sequence, and most importantly the two terminal C's, existed in a single-stranded form. A single-stranded CC may be crucial for formation of an initiation complex for (-) strand synthesis consisting of viral RdRP, mRNA, and the dinucleotide pGpG. JF - Virology AU - Chen, D AU - Barros, M AU - Spencer, E AU - Patton, J T AD - Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, 7 Center Drive, MSC 0720, Room 117, Bethesda, Maryland, 20892, USA. Y1 - 2001/04/10/ PY - 2001 DA - 2001 Apr 10 SP - 221 EP - 229 VL - 282 IS - 2 SN - 0042-6822, 0042-6822 KW - Oligoribonucleotides KW - 0 KW - RNA, Messenger KW - RNA, Viral KW - Index Medicus KW - Animals KW - RNA, Messenger -- chemistry KW - Genome, Viral KW - RNA, Messenger -- genetics KW - Haplorhini KW - RNA, Messenger -- biosynthesis KW - Base Pairing KW - Base Sequence KW - Oligoribonucleotides -- chemistry KW - Mutation -- genetics KW - Templates, Genetic KW - Oligoribonucleotides -- genetics KW - Cell Line KW - Virus Replication KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Consensus Sequence -- genetics KW - RNA, Viral -- biosynthesis KW - RNA, Viral -- chemistry KW - Rotavirus -- genetics KW - RNA, Viral -- genetics KW - Rotavirus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77031226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Features+of+the+3%27-consensus+sequence+of+rotavirus+mRNAs+critical+to+minus+strand+synthesis.&rft.au=Chen%2C+D%3BBarros%2C+M%3BSpencer%2C+E%3BPatton%2C+J+T&rft.aulast=Chen&rft.aufirst=D&rft.date=2001-04-10&rft.volume=282&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infectious cDNA Clone of Attenuated Langat Tick-Borne Flavivirus (Strain E5) and a 3' Deletion Mutant Constructed from It Exhibit Decreased Neuroinvasiveness in Immunodeficient Mice AN - 17888310; 5127273 AB - Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT) strain TP21, was recovered from ticks in Malaysia. Subsequently, it was tested as a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a large clinical trial its attenuation was confirmed but there was evidence of a low level of residual virulence. Thirty-five years ago further attenuation of LGT TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the genetic determinants of the further attenuation exhibited by E5 and to allow us to manipulate the genome of this virus for the purpose of developing a satisfactory live attenuated tick-borne flavivirus vaccine, we recovered infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus (clone 651) recovered from a full-length infectious cDNA clone was more attenuated in immunodeficient mice than that of its biologically derived E5 parent. Increase in attenuation was associated with three amino acid substitutions, two located in the structural protein E and one in nonstructural protein NS4B. Subsequently an even greater degree of attenuation was achieved by creating a viable 320 nucleotide deletion in the 3'-noncoding region of infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian Vero cells and it replicated to lower titer than its E5-651 parent. In addition, the E5 3' deletion mutant was less neuroinvasive in SCID mice than its E5-651 parent. Significantly, the deletion mutant proved to be 119,750 times less neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high level of attenuation, the E5 3' deletion mutant remained highly immunogenic and intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21. JF - Virology AU - Pletnev, A G AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, 20892, Maryland, apletnev@niaid.nih.gov Y1 - 2001/04/10/ PY - 2001 DA - 2001 Apr 10 SP - 288 EP - 300 PB - Academic Press VL - 282 IS - 2 SN - 0042-6822, 0042-6822 KW - mice KW - ticks KW - cDNA KW - NS4B protein KW - double prime E protein KW - CSA Neurosciences Abstracts; Genetics Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - ^AE protein KW - Genomes KW - Nucleotide sequence KW - Flavivirus KW - Virulence KW - Attenuation KW - Recombinants KW - Vaccines KW - Acari KW - Mutation KW - A 01100:Viruses KW - N3 11130:Neurovirology KW - V 22050:Viral genetics including virus reactivation KW - G 07313:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17888310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Infectious+cDNA+Clone+of+Attenuated+Langat+Tick-Borne+Flavivirus+%28Strain+E5%29+and+a+3%27+Deletion+Mutant+Constructed+from+It+Exhibit+Decreased+Neuroinvasiveness+in+Immunodeficient+Mice&rft.au=Pletnev%2C+A+G&rft.aulast=Pletnev&rft.aufirst=A&rft.date=2001-04-10&rft.volume=282&rft.issue=2&rft.spage=288&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/10.1006%2Fviro.2001.0846 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Acari; Flavivirus; Nucleotide sequence; Virulence; Vaccines; Genomes; Recombinants; Attenuation; Mutation DO - http://dx.doi.org/10.1006/viro.2001.0846 ER - TY - JOUR T1 - Update on the Use of Nonhuman Primate Models for Preclinical Testing of Gene Therapy Approaches Targeting Hematopoietic Cells AN - 17859457; 5109241 AB - Transfer of genes into hematopoietic stem cells or primary lymphocytes has been a primary focus of the gene therapy field for more than a decade because of the wide variety of congenital and acquired diseases that potentially could be cured by successful gene transfer into these cell populations. However, despite success in murine models and in vitro, progress has been slow, and early clinical trials were disappointing due to inefficient gene transfer into long-term repopulating cells. The unique predictive value of nonhuman primate or other large animal models has become more apparent, and major advances in gene transfer efficiency have been made by utilizing these powerful but expensive and complex systems. This review summarizes more recent findings from nonhuman primate investigations focusing on hematopoietic stem cells or lymphocytes as target populations, and highlights specific preclinical issues, including safety. Results from studies using standard retroviral vectors, lentiviral vectors, adenoviral vectors, and adeno-associated viral vectors are discussed. Judicious application of these models should continue to be a priority, and advances should now be tested in proof-of-concept clinical trials. JF - Human Gene Therapy AU - Donahue, R E AU - Dunbar, CE AD - Hematology Branch, NHLBI, Room 1B-05, 5 Research Court, Rockville, MD 20850, USA, donahuer@nhlbi.nih.gov Y1 - 2001/04/10/ PY - 2001 DA - 2001 Apr 10 SP - 607 EP - 617 VL - 12 IS - 6 SN - 1043-0342, 1043-0342 KW - Primates KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Stem cells KW - Gene therapy KW - Gene transfer KW - Reviews KW - Hemopoiesis KW - Lymphocytes KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17859457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Update+on+the+Use+of+Nonhuman+Primate+Models+for+Preclinical+Testing+of+Gene+Therapy+Approaches+Targeting+Hematopoietic+Cells&rft.au=Donahue%2C+R+E%3BDunbar%2C+CE&rft.aulast=Donahue&rft.aufirst=R&rft.date=2001-04-10&rft.volume=12&rft.issue=6&rft.spage=607&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Reviews; Lymphocytes; Stem cells; Hemopoiesis; Gene transfer ER - TY - JOUR T1 - Effect of nicotine on brain activation during performance of a working memory task AN - 17841037; 4870969 AB - Nicotine influences cognition and behavior, but the mechanisms by which these effects occur are unclear. By using positron emission tomography, we measured cognitive activation (increases in relative regional cerebral blood flow) during a working memory task [2-back task (2BT)] in 11 abstinent smokers and 11 ex-smokers. Assays were performed both after administration of placebo gum and 4-mg nicotine gum. Performance on the 2BT did not differ between groups in either condition, and the pattern of brain activation by the 2BT was consistent with reports in the literature. However, in the placebo condition, activation in ex-smokers predominated in the left hemisphere, whereas in smokers, it occurred in the right hemisphere. When nicotine was administered, activation was reduced in smokers but enhanced in ex-smokers. The lateralization of activation as a function of nicotine dependence suggests that chronic exposure to nicotine or withdrawal from nicotine affects cognitive strategies used to perform the memory task. Furthermore, the lack of enhancement of activation after nicotine administration in smokers likely reflects tolerance. JF - Proceedings of the National Academy of Sciences, USA AU - Ernst, M AU - Matochik, JA AU - Heishman, S J AU - Van Horn, JD AU - Jons, PH AU - Henningfield, JE AU - London, ED AD - Brain Imaging Center and Clinical Pharmacology and Therapeutics Branch, National Institute on Drug Abuse, Baltimore, MD 21224, mernst@intra.nida.nih.gov Y1 - 2001/04/10/ PY - 2001 DA - 2001 Apr 10 SP - 4728 EP - 4733 VL - 98 IS - 8 SN - 0027-8424, 0027-8424 KW - tolerance KW - activation KW - man KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Hemispheric laterality KW - Brain KW - Cognition KW - Smoking KW - Memory KW - Behavior KW - Nicotine KW - Positron emission tomography KW - Cerebral blood flow KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17841037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Effect+of+nicotine+on+brain+activation+during+performance+of+a+working+memory+task&rft.au=Ernst%2C+M%3BMatochik%2C+JA%3BHeishman%2C+S+J%3BVan+Horn%2C+JD%3BJons%2C+PH%3BHenningfield%2C+JE%3BLondon%2C+ED&rft.aulast=Ernst&rft.aufirst=M&rft.date=2001-04-10&rft.volume=98&rft.issue=8&rft.spage=4728&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nicotine; Brain; Memory; Cognition; Behavior; Positron emission tomography; Smoking; Cerebral blood flow; Hemispheric laterality ER - TY - JOUR T1 - Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1. AN - 77020660; 11124944 AB - The real time dynamics of vanilloid-induced cytotoxicity and the specific deletion of nociceptive neurons expressing the wild-type vanilloid receptor (VR1) were investigated. VR1 was C-terminally tagged with either the 27-kDa enhanced green fluorescent protein (eGFP) or a 12-amino acid epsilon-epitope. Upon exposure to resiniferatoxin, VR1eGFP- or VR1epsilon-expressing cells exhibited pharmacological responses similar to those of cells expressing the untagged VR1. Within seconds of vanilloid exposure, the intracellular free calcium ([Ca(2+)](i)) was elevated in cells expressing VR1. A functional pool of VR1 also was localized to the endoplasmic reticulum that, in the absence of extracellular calcium, also was capable of releasing calcium upon agonist treatment. Confocal imaging disclosed that resiniferatoxin treatment induced vesiculation of the mitochondria and the endoplasmic reticulum ( approximately 1 min), nuclear membrane disruption (5-10 min), and cell lysis (1-2 h). Nociceptive primary sensory neurons endogenously express VR1, and resiniferatoxin treatment induced a sudden increase in [Ca(2+)](i) and mitochondrial disruption which was cell-selective, as glia and non-VR1-expressing neurons were unaffected. Early hallmarks of cytotoxicity were followed by specific deletion of VR1-expressing cells. These data demonstrate that vanilloids disrupt vital organelles within the cell body and, if administered to sensory ganglia, may be employed to rapidly and selectively delete nociceptive neurons. JF - The Journal of biological chemistry AU - Olah, Z AU - Szabo, T AU - Karai, L AU - Hough, C AU - Fields, R D AU - Caudle, R M AU - Blumberg, P M AU - Iadarola, M J AD - Neuronal Gene Expression Unit, Pain and Neurosensory Mechanisms Branch, NIDCR, the Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. zoltan.olah@nih.gov Y1 - 2001/04/06/ PY - 2001 DA - 2001 Apr 06 SP - 11021 EP - 11030 VL - 276 IS - 14 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Luminescent Proteins KW - Receptors, Drug KW - TRPV Cation Channels KW - TRPV1 receptor KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - COS Cells KW - Biological Transport KW - Capsaicin -- pharmacology KW - Receptors, Drug -- metabolism KW - Receptors, Drug -- agonists KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77020660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Ligand-induced+dynamic+membrane+changes+and+cell+deletion+conferred+by+vanilloid+receptor+1.&rft.au=Olah%2C+Z%3BSzabo%2C+T%3BKarai%2C+L%3BHough%2C+C%3BFields%2C+R+D%3BCaudle%2C+R+M%3BBlumberg%2C+P+M%3BIadarola%2C+M+J&rft.aulast=Olah&rft.aufirst=Z&rft.date=2001-04-06&rft.volume=276&rft.issue=14&rft.spage=11021&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identification of cell-binding sites on the Laminin alpha 5 N-terminal domain by site-directed mutagenesis. AN - 77018586; 11098055 AB - The newly discovered laminin alpha(5) chain is a multidomain, extracellular matrix protein implicated in various biological functions such as the development of blood vessels and nerves. The N-terminal globular domain of the laminin alpha chains has an important role for biological activities through interactions with cell surface receptors. In this study, we identified residues that are critical for cell binding within the laminin alpha(5) N-terminal globular domain VI (approximately 270 residues) using site-directed mutagenesis and synthetic peptides. A recombinant protein of domain VI and the first four epidermal growth factor-like repeats of domain V, generated in a mammalian expression system, was highly active for HT-1080 cell binding, while a recombinant protein consisting of only the epidermal growth factor-like repeats showed no cell binding. By competition analysis with synthetic peptides for cell binding, we identified two sequences: S2, (123)GQVFHVAYVLIKF(135) and S6, (225)RDFTKATNIRLRFLR(239), within domain VI that inhibited cell binding to domain VI. Alanine substitution mutagenesis indicated that four residues (Tyr(130), Arg(225), Lys(229), and Arg(239)) within these two sequences are crucial for cell binding. Real-time heparin-binding kinetics of the domain VI mutants analyzed by surface plasmon resonance indicated that Arg(239) of S6 was critical for both heparin and cell binding. In addition, cell binding to domain VI was inhibited by heparin/heparan sulfate, which suggests an overlap of cell and heparin-binding sites. Furthermore, inhibition studies using integrin subunit monoclonal antibodies showed that integrin alpha(3)beta(1) was a major receptor for domain VI binding. Our results provide evidence that two sites spaced about 90 residues apart within the laminin alpha(5) chain N-terminal globular domain VI are critical for cell surface receptor binding. JF - The Journal of biological chemistry AU - Nielsen, P K AU - Yamada, Y AD - Molecular Biology Section, Craniofacial Developmental Biology and Regeneration Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892-4370, USA. Y1 - 2001/04/06/ PY - 2001 DA - 2001 Apr 06 SP - 10906 EP - 10912 VL - 276 IS - 14 SN - 0021-9258, 0021-9258 KW - Laminin KW - 0 KW - laminin alpha5 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Binding Sites -- genetics KW - Protein Binding KW - Laminin -- metabolism KW - Laminin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77018586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+cell-binding+sites+on+the+Laminin+alpha+5+N-terminal+domain+by+site-directed+mutagenesis.&rft.au=Nielsen%2C+P+K%3BYamada%2C+Y&rft.aulast=Nielsen&rft.aufirst=P&rft.date=2001-04-06&rft.volume=276&rft.issue=14&rft.spage=10906&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of antibodies to HAV 3C proteinase in experimentally infected chimpanzees and in naturally infected children AN - 17866164; 5108200 AB - Commercial assays for the diagnosis of hepatitis A detect antibody to hepatitis A virus (anti-HAV), but they cannot discriminate between antibody resulting from infection and antibody induced by inactivated vaccine. With the licensing and increasing use of inactivated hepatitis A vaccines, there is a need for a test to distinguish between infection and vaccination. Since antibodies to viral non-structural proteins are elicited by infection but not by vaccination with inactivated vaccine, we developed and evaluated a test for such antibodies. The antibody response to the non-structural 3C proteinase (anti-3C) of virus HAV was studied by ELISA in chimpanzees experimentally infected with virulent (wild type) or with attenuated HAV strains and in children who received inactivated HAV vaccine or placebo during a vaccination trial in Nicaragua. Anti-3C was detected in 89% of 18 chimpanzees infected with wild-type HAV strains and 27% of 26 chimpanzees infected with attenuated HAV strains. There was a direct correlation between severity of hepatitis and magnitude of the anti-3C response. In the vaccine trial, anti-3C was detected only in children who were infected with HAV during the study; IgG anti-3C persisted for at least 15 months after infection in one child. Vaccinated and uninfected children remained negative for anti-3C. The anti-3C response can be regarded as an indicator of viral replication. Its detection should be useful for distinguishing between antibody acquired in response to HAV infection and antibody induced by immunization with inactivated vaccine. JF - Vaccine AU - Kabrane-Lazizi, Y AU - Emerson, SU AU - Herzog, C AU - Purcell, R H AD - Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, rpurcell@niaid.nih.gov Y1 - 2001/04/06/ PY - 2001 DA - 2001 Apr 06 SP - 2878 EP - 2883 VL - 19 IS - 20-22 SN - 0264-410X, 0264-410X KW - man KW - Chimpanzee KW - HAV 3C proteinase KW - Nicaragua KW - Pan troglodytes KW - anti-3C response KW - hepatitis A virus KW - proteinase KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - Enzyme-linked immunosorbent assay KW - Hepatitis A virus KW - Antibody response KW - Children KW - Infection KW - Detection KW - Proteinase KW - Vaccines KW - F 06807:Active immunization KW - A 01114:Viruses KW - V 22091:Immunological techniques & reagents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17866164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Detection+of+antibodies+to+HAV+3C+proteinase+in+experimentally+infected+chimpanzees+and+in+naturally+infected+children&rft.au=Kabrane-Lazizi%2C+Y%3BEmerson%2C+SU%3BHerzog%2C+C%3BPurcell%2C+R+H&rft.aulast=Kabrane-Lazizi&rft.aufirst=Y&rft.date=2001-04-06&rft.volume=19&rft.issue=20-22&rft.spage=2878&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pan troglodytes; Hepatitis A virus; Vaccines; Antibody response; Infection; Enzyme-linked immunosorbent assay; Detection; Proteinase; Children ER - TY - JOUR T1 - Gene structure and enzymatic activity of mouse eosinophil-associated ribonuclease 2. AN - 77075473; 11311552 AB - Mouse eosinophil-associated ribonuclease-2 (mEAR-2) is one of a cluster of genes identified in the genome of the mouse Mus musculus that are highly divergent orthologs of the primate ribonucleases, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP). Northern analysis revealed expression of genes hybridizing to mEAR-2 in mouse lung, liver and spleen tissues. We obtained full-length cDNA by hybridization screening of mouse eosinophil and lung cDNA libraries and by rapid amplification of cDNA ends (RACE) from liver, spleen and lung RNA. Using these methods we have isolated the 195 base pair (bp) 3' untranslated region (UTR) that includes a typical polyadenylation signal preceding a poly A tail and the 5' UTR which includes 63-71 bp and three distinct transcriptional start sites. Using unidirectional PCR we isolated a 361-bp 5' promoter region and delineated the intronic / exonic boundaries which include a non-coding exon 1, a single intron, and a coding exon 2, a structure that is typical of genes of the RNase A superfamily. Consensus sites for PU.1 and EoTF, both active as intronic enhancer elements of the gene encoding EDN, are also present in the intron of the gene encoding mEAR-2. The catalytic activity of recombinant baculovirus-derived mEAR-2 is similar to that of rhEDN from this source, with catalytic constants k(cat)/K(m)=5.6x10(6) M(-1) s(-1) and 10.5x10(6) M(-1) s(-1), respectively, against a standard yeast tRNA substrate. Sequence analysis of the non-coding regions and enzymatic characterization of the gene product provide further evidence indicating that mEAR-2 is a structural and functional ortholog of primate EDNs and ECPs. JF - Gene AU - McDevitt, A L AU - Deming, M S AU - Rosenberg, H F AU - Dyer, K D AD - Eosinophil Biology Unit, Laboratory of Host Defenses 10/11N104, NIAID / National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1886, USA. Y1 - 2001/04/04/ PY - 2001 DA - 2001 Apr 04 SP - 23 EP - 30 VL - 267 IS - 1 SN - 0378-1119, 0378-1119 KW - Blood Proteins KW - 0 KW - DNA, Complementary KW - Eosinophil Granule Proteins KW - RNA, Messenger KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Animals KW - Blotting, Northern KW - DNA, Complementary -- genetics KW - Humans KW - Transcription, Genetic KW - Mice KW - Tissue Distribution KW - Sequence Analysis, DNA KW - Recombinant Proteins -- genetics KW - RNA, Messenger -- genetics KW - Ribonucleases -- metabolism KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Recombinant Proteins -- metabolism KW - DNA -- genetics KW - Ribonucleases -- genetics KW - Molecular Sequence Data KW - DNA, Complementary -- chemistry KW - DNA -- chemistry KW - Cell Line KW - Blood Proteins -- metabolism KW - Genes -- genetics KW - Blood Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77075473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Gene+structure+and+enzymatic+activity+of+mouse+eosinophil-associated+ribonuclease+2.&rft.au=McDevitt%2C+A+L%3BDeming%2C+M+S%3BRosenberg%2C+H+F%3BDyer%2C+K+D&rft.aulast=McDevitt&rft.aufirst=A&rft.date=2001-04-04&rft.volume=267&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF306664; GENBANK; AF306665 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-specific phosphorylation of human p53 protein determined by mass spectrometry. AN - 77050830; 11300786 AB - Human recombinant p53 (r-p53) protein was studied by mass spectrometry (MS) to determine site-specific posttranslational differences between basal and hyperphosphorylated r-p53. Wild-type p53 was basally expressed after baculovirus infection while a parallel preparation was treated with the phosphatase inhibitor okadaic acid during the terminal stages of expression to create a hyperphosphorylated form of p53 known for its higher DNA binding and transcriptional activation. After immunoaffinity and HPLC purification, MALDI/MS measured a higher molecular mass for r-p53 from okadaic acid treatment relative to control, suggesting a higher phosphorylation state. This was supported by an acidic shift of r-p53 isoforms separated by gel isoelectric focusing. Employing a variety of mass spectrometric analyses combined with separation and affinity techniques, six specific phosphorylation sites of p53 were identified. The MS data indicated that hyperphosphorylated p53 showed a higher degree of phosphorylation than basal p53 at specific amino- and carboxy-terminal sites. In particular, ESI-MS demonstrated that Ser(315) was entirely phosphorylated after okadaic acid treatment, as confirmed biochemically by CDK2 kinase assay and by isoelectric focusing. In summary, MS analysis uniquely revealed increased, site-specific phosphorylations on p53 after phosphatase inhibition, particularly at Ser(315), which may be critical molecular events in defining p53 activity. JF - Biochemistry AU - Merrick, B A AU - Zhou, W AU - Martin, K J AU - Jeyarajah, S AU - Parker, C E AU - Selkirk, J K AU - Tomer, K B AU - Borchers, C H AD - Laboratory of Molecular Carcinogenesis and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/04/03/ PY - 2001 DA - 2001 Apr 03 SP - 4053 EP - 4066 VL - 40 IS - 13 SN - 0006-2960, 0006-2960 KW - Enzyme Inhibitors KW - 0 KW - Peptide Fragments KW - Phosphopeptides KW - Recombinant Proteins KW - Tumor Suppressor Protein p53 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Serine KW - 452VLY9402 KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Spodoptera -- genetics KW - Phosphopeptides -- genetics KW - Recombinant Proteins -- biosynthesis KW - Peptide Fragments -- genetics KW - Humans KW - Amino Acid Sequence KW - Hydrolysis KW - Serine -- metabolism KW - Chromatography, High Pressure Liquid KW - Phosphorylation -- drug effects KW - Baculoviridae -- genetics KW - Phosphopeptides -- metabolism KW - Recombinant Proteins -- metabolism KW - Chromatography, Liquid KW - Molecular Sequence Data KW - Okadaic Acid -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization -- methods KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77050830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Site-specific+phosphorylation+of+human+p53+protein+determined+by+mass+spectrometry.&rft.au=Merrick%2C+B+A%3BZhou%2C+W%3BMartin%2C+K+J%3BJeyarajah%2C+S%3BParker%2C+C+E%3BSelkirk%2C+J+K%3BTomer%2C+K+B%3BBorchers%2C+C+H&rft.aulast=Merrick&rft.aufirst=B&rft.date=2001-04-03&rft.volume=40&rft.issue=13&rft.spage=4053&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leptin-regulated endocannabinoids are involved in maintaining food intake AN - 856763085; 13743414 AB - Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as a-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors, cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y. CB1 cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus, and marijuana and anandamide stimulate food intake. Here we show that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild-type but not knockout mice. Furthermore, defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin. JF - Nature AU - Di Marzo, Vincenzo AU - Goparaju, Sravan K AU - Wang, Lei AU - Liu, Jie AU - Batkai, Sandor AU - Jarai, Zoltan AU - Fezza, Filomena AU - Miura, Grant I AU - Palmiter, Richard D AU - Sugiura, Takayuki AU - Kunos, George AD - [1] Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA [2] Present address: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, MSC-8115, Bethesda, Maryland 20892-8115, USA. PY - 2001 SP - 822 EP - 825 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 410 IS - 6830 SN - 0028-0836, 0028-0836 KW - Sustainability Science Abstracts KW - Rats KW - obesity KW - Mice KW - Mutation KW - Nutrition KW - Hormones KW - M3 1010:Issues in Sustainable Development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856763085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Leptin-regulated+endocannabinoids+are+involved+in+maintaining+food+intake&rft.au=Di+Marzo%2C+Vincenzo%3BGoparaju%2C+Sravan+K%3BWang%2C+Lei%3BLiu%2C+Jie%3BBatkai%2C+Sandor%3BJarai%2C+Zoltan%3BFezza%2C+Filomena%3BMiura%2C+Grant+I%3BPalmiter%2C+Richard+D%3BSugiura%2C+Takayuki%3BKunos%2C+George&rft.aulast=Di+Marzo&rft.aufirst=Vincenzo&rft.date=2001-04-02&rft.volume=410&rft.issue=6830&rft.spage=822&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35071088 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - Rats; obesity; Mice; Hormones; Nutrition; Mutation DO - http://dx.doi.org/10.1038/35071088 ER - TY - JOUR T1 - Expression of proneural and neurogenic genes in the zebrafish lateral line primordium correlates with selection of hair cell fate in neuromasts. AN - 85270157; pmid-11287207 AB - Expression of a mouse atonal homologue, math1, defines cells with the potential to become sensory hair cells in the mouse inner ear (Science 284 (1999) 1837) and Notch signaling limits the number of cells that are permitted to adopt this fate (Nat. Genet. 21 (1999) 289; J. Neurocytol. 28 (1999) 809). Failure of lateral inhibition mediated by Notch signaling is associated with an overproduction of ear hair cells in the zebrafish mind bomb (mib) and deltaA mutants (Development 125 (1998a) 4637; Development 126 (1999) 5669), suggesting a similar role for these genes in limiting the number of hair cells in the zebrafish ear. This study extends the analysis of proneural and neurogenic gene expression to the lateral line system, which detects movement via clusters of related sensory hair cells in specialized structures called neuromasts. We have compared the expression of a zebrafish atonal homologue, zath1, and neurogenic genes, deltaA, deltaB and notch3, in neuromasts and the posterior lateral line primordium (PLLP) of wild-type and mib mutant embryos. We describe progressive restriction of proneural and neurogenic gene expression in the migrating PLLP that appears to correlate with selection of hair cell fate in maturing neuromasts. In mib mutants there is a failure to restrict expression of zath1 and Delta homologues in the neuromasts revealing similarities with the phenotype previously described in the ear. JF - Mechanisms of Development AU - Itoh, M AU - Chitnis, A B AD - Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892, USA. PY - 2001 SP - 263 EP - 266 VL - 102 IS - 1-2 SN - 0925-4773, 0925-4773 KW - Cell Lineage KW - Hair Cells KW - Animal KW - Ear KW - Membrane Proteins KW - Zebrafish KW - In Situ Hybridization KW - Proto-Oncogene Proteins KW - Neurons KW - Support, Non-U.S. Gov't KW - Tubulin KW - Time Factors KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85270157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mechanisms+of+Development&rft.atitle=Expression+of+proneural+and+neurogenic+genes+in+the+zebrafish+lateral+line+primordium+correlates+with+selection+of+hair+cell+fate+in+neuromasts.&rft.au=Itoh%2C+M%3BChitnis%2C+A+B&rft.aulast=Itoh&rft.aufirst=M&rft.date=2001-04-01&rft.volume=102&rft.issue=1-2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+Development&rft.issn=09254773&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Computational Models of Antibody-Based Tumor Imaging and Treatment Protocols AN - 831174269; 13866380 AB - We present improved computational models for investigating monoclonal antibody-based protocols for diagnostic imaging and therapy of solid tumors. Our earlier models used a boundary condition (Dirichlet) that specified concentrations of diffusing molecular species at the interface between a prevascular tumor nodule and surrounding normal tissue. Here we introduce a concentration-dependent flux boundary condition with finite rates of diffusion in the normal tissue. We then study the effects of this new condition on the tumor's temporal uptake and spatial distribution of radiolabeled targeting agents. We compare these results to ones obtained with the Dirichlet boundary condition and also conduct parameter sensitivity analyses. Introducing finite diffusivity for any molecular species in normal tissue retards its delivery to and removal from the tumor nodule. Effects are protocol- and dose regimen-dependent; generally, however, mean radionuclide concentration and tumor-to-blood ratio declined, whereas relative exposure and mean residence time increased. Finite diffusivity exacerbates the negative effects of antigen internalization. Also, the sensitivity analyses show that mean concentration and tumor-to-blood ratio are quite sensitive to transcapillary permeability and lymphatic efflux values, yet relatively insensitive to precise values of diffusion coefficients. Our analysis underscores that knowledge of antigen internalization rates and doses required to saturate antigen in the tumor will be important for exploiting antibody-based imaging and treatment approaches. [copy 2001 Biomedical Engineering Society. PAC01: 8758-b, 8710+e, 8753-j JF - Annals of Biomedical Engineering AU - Praxmarer, Meinrad AU - Sung, Cynthia AU - Bungay, Peter M AU - van Osdol, William W AD - Division of Bioengineering and Physical Science, Office of Research Services, National Institutes of Health, Bethesda, MD Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 340 EP - 358 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 29 IS - 4 SN - 0090-6964, 0090-6964 KW - Biotechnology and Bioengineering Abstracts KW - Molecular modelling KW - Mathematical models KW - Spatial distribution KW - Solid tumors KW - Tumors KW - imaging KW - Nodules KW - Permeability KW - Antigen (tumor-associated) KW - Boundaries KW - Radioisotopes KW - Diffusion coefficient KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/831174269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Biomedical+Engineering&rft.atitle=Computational+Models+of+Antibody-Based+Tumor+Imaging+and+Treatment+Protocols&rft.au=Praxmarer%2C+Meinrad%3BSung%2C+Cynthia%3BBungay%2C+Peter+M%3Bvan+Osdol%2C+William+W&rft.aulast=Praxmarer&rft.aufirst=Meinrad&rft.date=2001-04-01&rft.volume=29&rft.issue=4&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=Annals+of+Biomedical+Engineering&rft.issn=00906964&rft_id=info:doi/10.1114%2F1.1359453 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2015-03-19 N1 - SubjectsTermNotLitGenreText - Permeability; Molecular modelling; Mathematical models; Spatial distribution; Solid tumors; Antigen (tumor-associated); Radioisotopes; Boundaries; Diffusion coefficient; Tumors; imaging; Nodules DO - http://dx.doi.org/10.1114/1.1359453 ER - TY - JOUR T1 - Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug Screen. AN - 77069520; 11309351 AB - To determine the expression of three targets of 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) in human tumor cell lines and to compare these with the 50% growth inhibition concentrations (GI(50)) from the National Cancer Institute database. Thymidine kinase (TK) activity was assessed by conversion of [(3)H]thymidine to [(3)H]TMP. Thymidylate synthase (TS) protein expression was determined by Western analysis. TS and dihydropyrimidine dehydrogenase (DPD) mRNA expression were measured by quantitative reverse transcription-PCR. The median (range) for the targets were as follows: 5-FU GI(50), 20.8 microM (0.8-536); FdUrd GI(50), 0.75 microM (0.25-237); TK, 0.93 nmol/min/mg (0.16-5.7); in arbitrary units: TS protein, 0.41 (0.05-2.95); TS mRNA, 1.05 (0.12-6.41); and DPD mRNA, 1.09 (0.00-24.4). A moderately strong correlation was noted between 5-FU and FdUrd GI(50)s (r = 0.60), whereas a weak-moderate correlation was seen between TS mRNA and protein expression (r = 0.45). Neither TS expression nor TK activity correlated with 5-FU or FdUrd GI(50)s, whereas lines with lower DPD expression tended to be more sensitive to 5-FU. Cell lines with faster doubling times and wild-type p53 were significantly more sensitive to 5-FU and FDURD: The lack of correlation may in part be attributable to the influence of downstream factors such as p53, the observation that the more sensitive cell lines with faster doubling times also had higher TS levels, and the standard procedure of the screen that uses a relatively short (48-h) drug exposure. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Grem, J L AU - Danenberg, K D AU - Behan, K AU - Parr, A AU - Young, L AU - Danenberg, P V AU - Nguyen, D AU - Drake, J AU - Monks, A AU - Allegra, C J AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute at the National Naval Medical Center, Bethesda, Maryland 20889, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 999 EP - 1009 VL - 7 IS - 4 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Floxuridine KW - 039LU44I5M KW - DNA KW - 9007-49-2 KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Fluorouracil KW - U3P01618RT KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - United States KW - Mutation -- drug effects KW - Animals KW - Drug Screening Assays, Antitumor KW - Humans KW - RNA, Messenger -- drug effects KW - Cell Division -- drug effects KW - DNA -- biosynthesis KW - DNA -- drug effects KW - Thymidine -- metabolism KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - National Institutes of Health (U.S.) KW - Databases, Factual KW - Tumor Suppressor Protein p53 -- genetics KW - Cell Line KW - Thymidylate Synthase -- genetics KW - Oxidoreductases -- genetics KW - Floxuridine -- pharmacology KW - Oxidoreductases -- metabolism KW - Thymidine Kinase -- metabolism KW - Fluorouracil -- pharmacology KW - Thymidylate Synthase -- metabolism KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77069520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Thymidine+kinase%2C+thymidylate+synthase%2C+and+dihydropyrimidine+dehydrogenase+profiles+of+cell+lines+of+the+National+Cancer+Institute%27s+Anticancer+Drug+Screen.&rft.au=Grem%2C+J+L%3BDanenberg%2C+K+D%3BBehan%2C+K%3BParr%2C+A%3BYoung%2C+L%3BDanenberg%2C+P+V%3BNguyen%2C+D%3BDrake%2C+J%3BMonks%2C+A%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=2001-04-01&rft.volume=7&rft.issue=4&rft.spage=999&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclophosphamide attenuates the degenerative changes induced by CSF from patients with amyotrophic lateral sclerosis in the neonatal rat spinal cord. AN - 77068274; 11311291 AB - Our earlier studies have shown that cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), when intrathecally injected into the neonatal rats, produces an aberrant phosphorylation of neurofilaments (NF) in the ventral horn neurons and reactive astrogliosis in the spinal cord. We wanted to investigate the effect of cyclophosphamide in the spinal cords of neonatal rats exposed to ALS-CSF. A single dose (5 microg in 5 microl saline) of cyclophosphamide was injected, 24 h after the administration of CSF samples from ALS and non-ALS neurological patients into the spinal subarachnoid space of 3-day-old rat pups. Rats were sacrificed after a period of 24 h, and stained with antibodies against the phosphorylated NF (SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Cyclophosphamide treatment resulted in a 50% decrease in the number of SMI-31 stained neuronal soma in ventral horns of spinal cords of ALS-CSF exposed rats. This was accompanied by a decrease in the number of GFAP immunoreactive astrocytes. Furthermore, lactate dehydrogenase (LDH) activity was also decreased significantly, following cyclophosphamide treatment. These results suggest that cyclophosphamide could exert a neuroprotective effect against the neurotoxic action of factor(s) present in the ALS-CSF. JF - Journal of the neurological sciences AU - Shahani, N AU - Gourie-Devi, M AU - Nalini, A AU - Raju, T R AD - Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS) P.O. Box 2900, Hosur Road, 560 029, Bangalore, India. Y1 - 2001/04/01/ PY - 2001 DA - 2001 Apr 01 SP - 109 EP - 118 VL - 185 IS - 2 SN - 0022-510X, 0022-510X KW - Cerebrospinal Fluid Proteins KW - 0 KW - Glial Fibrillary Acidic Protein KW - Immunosuppressive Agents KW - Neurofilament Proteins KW - Neuroprotective Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Animals KW - Gliosis -- physiopathology KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - L-Lactate Dehydrogenase -- drug effects KW - Astrocytes -- drug effects KW - Glial Fibrillary Acidic Protein -- metabolism KW - Neurofilament Proteins -- metabolism KW - Animals, Newborn -- metabolism KW - Phosphorylation -- drug effects KW - Rats KW - Gliosis -- prevention & control KW - Glial Fibrillary Acidic Protein -- drug effects KW - Rats, Wistar KW - Gliosis -- chemically induced KW - Astrocytes -- pathology KW - Immunohistochemistry KW - L-Lactate Dehydrogenase -- metabolism KW - Neurofilament Proteins -- drug effects KW - Cerebrospinal Fluid Proteins -- pharmacology KW - Amyotrophic Lateral Sclerosis -- cerebrospinal fluid KW - Nerve Degeneration -- physiopathology KW - Anterior Horn Cells -- pathology KW - Nerve Degeneration -- chemically induced KW - Nerve Degeneration -- prevention & control KW - Anterior Horn Cells -- drug effects KW - Amyotrophic Lateral Sclerosis -- drug therapy KW - Neuroprotective Agents -- pharmacology KW - Immunosuppressive Agents -- pharmacology KW - Cyclophosphamide -- pharmacology KW - Amyotrophic Lateral Sclerosis -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77068274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+neurological+sciences&rft.atitle=Cyclophosphamide+attenuates+the+degenerative+changes+induced+by+CSF+from+patients+with+amyotrophic+lateral+sclerosis+in+the+neonatal+rat+spinal+cord.&rft.au=Shahani%2C+N%3BGourie-Devi%2C+M%3BNalini%2C+A%3BRaju%2C+T+R&rft.aulast=Shahani&rft.aufirst=N&rft.date=2001-04-01&rft.volume=185&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+neurological+sciences&rft.issn=0022510X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent inactivation of the TP53 gene in esophageal squamous cell carcinoma from a high-risk population in China. AN - 77064652; 11309337 AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers worldwide, and north central China has some of the highest rates in the world. Previous studies from tumors in this area of China have shown high frequencies of allelic loss on chromosome 17p13-11, which includes the region where the TP53 gene is found. We examined 56 ESCC patients using single-strand conformation polymorphism and DNA sequencing to assess the frequency and spectrum of TP53 mutation and the association between allelic loss at microsatellite marker TP53 and TP53 mutations. Ninety-six % of cases were found to have at least one genetic alteration, including TP53 mutation (77%), allelic loss within the TP53 gene (73%), and/or loss of heterozygosity at the TP53 microsatellite marker (80%); 75% had two or more such alterations, including 59% with both a point mutation and an intragenic allelic loss ("two hits"). The majority of mutations observed were in exon 5, where the most common type of nucleotide substitution was a G:C-->A:T or C:G-->T:A transition, including half that occurred at CpG sites. Allelic loss was most commonly found in exon 4 but was very common in exon 5 as well. Taken together, the multiple genetic alterations of TP53 in this population at high risk for ESCC indicate that there is a very high degree of genetic instability in these tumors, that TP53 is a primary target for inactivation, and that this tumor suppressor gene plays a critical role in the carcinogenesis process for ESCC. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Hu, N AU - Huang, J AU - Emmert-Buck, M R AU - Tang, Z Z AU - Roth, M J AU - Wang, C AU - Dawsey, S M AU - Li, G AU - Li, W J AU - Wang, Q H AU - Han, X Y AU - Ding, T AU - Giffen, C AU - Goldstein, A M AU - Taylor, P R AD - Divisions of clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 883 EP - 891 VL - 7 IS - 4 SN - 1078-0432, 1078-0432 KW - Genetic Markers KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Gene Frequency KW - Polymorphism, Genetic KW - Exons KW - Gene Silencing KW - Humans KW - Aged KW - Loss of Heterozygosity KW - Risk Factors KW - China -- epidemiology KW - Adult KW - Middle Aged KW - Mutation KW - Female KW - Male KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77064652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Frequent+inactivation+of+the+TP53+gene+in+esophageal+squamous+cell+carcinoma+from+a+high-risk+population+in+China.&rft.au=Hu%2C+N%3BHuang%2C+J%3BEmmert-Buck%2C+M+R%3BTang%2C+Z+Z%3BRoth%2C+M+J%3BWang%2C+C%3BDawsey%2C+S+M%3BLi%2C+G%3BLi%2C+W+J%3BWang%2C+Q+H%3BHan%2C+X+Y%3BDing%2C+T%3BGiffen%2C+C%3BGoldstein%2C+A+M%3BTaylor%2C+P+R&rft.aulast=Hu&rft.aufirst=N&rft.date=2001-04-01&rft.volume=7&rft.issue=4&rft.spage=883&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of tumor necrosis factor on toxicity and cytokine production after isolated hepatic perfusion. AN - 77062117; 11309322 AB - Isolated limb or liver perfusion with tumor necrosis factor (TNF) and melphalan results in regression of advanced cancers in the majority of treated patients. However, the contribution of TNF to the efficacy of isolation perfusion with melphalan has not been demonstrated conclusively in random assignment trials. Furthermore, TNF is an inflammatory cytokine and may be associated with significant systemic and regional toxicity. This study was conducted to characterize the toxicity and secondary cytokine production attributable to TNF by comparing these parameters in patients undergoing isolated hepatic perfusion (IHP) using melphalan with or without TNF. Thirty-two patients with unresectable colorectal cancer confined to the liver underwent a 60-min hyperthermic IHP using 1.5 mg/kg melphalan alone (n = 17) or with 1.0 mg of TNF (n = 15) with inflow via the gastroduodenal artery and outflow via an isolated segment of inferior vena cava. Complete vascular isolation was confirmed using the I-131 radiolabeled albumin-monitoring technique. Post-IHP parameters of hepatic and systemic toxicity and cytokine levels [TNF, interleukin (IL)-6 and IL-8] in perfusate and serum were measured. Levels of IL-6 and IL-8 in perfusate at the end of the 60-min IHP were significantly higher in TNF-treated patients (P < or = 0.001). Peak systemic IL-6 and IL-8 levels post-IHP were also significantly higher in TNF-treated compared with non-TNF-treated patients (P < 0.0001) by 28- and 268-fold, respectively. The peak levels of these cytokines were associated with significantly lower systolic blood pressure and higher heart rate and mean pulmonary artery blood pressure in TNF-treated patients during the first 48 h post-IHP (P < or = 0.03). Serum bilirubin levels were significantly higher (P = 0.017) and platelets lower (P = 0.03) in TNF-treated compared with non-TNF-treated patients. However, elevations in aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were not significantly different between groups and returned toward baseline within 1 week after IHP. Addition of TNF to melphalan during IHP results in significant differences in post-IHP production of IL-6 and IL-8 with associated changes in mean arterial blood pressure and greater regional toxicity, as reflected in higher levels of serum bilirubin. However, these measurable differences were transient and did not appear to be of major clinical consequence. Prior to its routine use, the benefit of TNF in isolation perfusion should be demonstrated in random assignment trials. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Lans, T E AU - Bartlett, D L AU - Libutti, S K AU - Gnant, M F AU - Liewehr, D J AU - Venzon, D J AU - Turner, E M AU - Alexander, H R AD - Surgery Branch, Division of Clinical Sciences and the Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 784 EP - 790 VL - 7 IS - 4 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Interleukin-6 KW - Interleukin-8 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Analysis of Variance KW - Perfusion KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Melphalan -- therapeutic use KW - Male KW - Female KW - Tumor Necrosis Factor-alpha -- toxicity KW - Liver -- drug effects KW - Colorectal Neoplasms -- metabolism KW - Interleukin-6 -- metabolism KW - Liver -- metabolism KW - Interleukin-8 -- metabolism KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77062117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Role+of+tumor+necrosis+factor+on+toxicity+and+cytokine+production+after+isolated+hepatic+perfusion.&rft.au=Lans%2C+T+E%3BBartlett%2C+D+L%3BLibutti%2C+S+K%3BGnant%2C+M+F%3BLiewehr%2C+D+J%3BVenzon%2C+D+J%3BTurner%2C+E+M%3BAlexander%2C+H+R&rft.aulast=Lans&rft.aufirst=T&rft.date=2001-04-01&rft.volume=7&rft.issue=4&rft.spage=784&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Halothane-induced liver injury in outbred guinea pigs: role of trifluoroacetylated protein adducts in animal susceptibility. AN - 77057750; 11304124 AB - Halothane causes a mild form of liver injury in guinea pigs that appears to model the hepatotoxicity seen in approximately 20% of patients treated with this drug. In previous studies, it was concluded that the increased susceptibility of some outbred guinea pigs to halothane-induced liver injury is not caused by their inherent ability to metabolize halothane to form toxic levels of trifluoroacetylated protein adducts in the liver. In this study, we reevaluated the role of trifluoroacetylated protein adducts in halothane-induced liver injury in guinea pigs. Male outbred Hartley guinea pigs were treated with halothane intraperitoneally. On the basis of serum alanine aminotransferase levels and liver histology, treated animals were designated as being susceptible, mildly susceptible, or resistant to halothane. Immunoblot studies with the use of anti-trifluoroacetylated antibodies showed that susceptible guinea pigs for the most part had higher levels of trifluoroacetylated protein adducts in the liver 48 h after treatment with halothane than did less susceptible animals. In support of this finding, the level of trifluoroacetylated protein adducts detected immunochemically in the sera of treated guinea pigs correlated with sera levels of alanine aminotransferase activity. In addition, the levels of cytochrome P450 2A-related protein but not those of other cytochrome P450 isoforms, measured by immunoblot analysis with isoform-specific antibodies, correlated with the amount of trifluoroacetylated protein adducts detected in the livers of guinea pigs 8 h after halothane administration. The results of this study indicate that the susceptibility of outbred guinea pigs to halothane-induced liver injury is related to an enhanced ability to metabolize halothane in the liver to form relatively high levels of trifluoroacetylated protein adducts. They also suggest that cytochrome P450 2A-related protein might have a major role in catalyzing the formation of trifluoroacetylated protein adducts in the liver of susceptible guinea pigs. Similar mechanisms may be important in humans. JF - Chemical research in toxicology AU - Bourdi, M AU - Amouzadeh, H R AU - Rushmore, T H AU - Martin, J L AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1760, USA. Bourdim@nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 362 EP - 370 VL - 14 IS - 4 SN - 0893-228X, 0893-228X KW - Anesthetics, Inhalation KW - 0 KW - DNA Primers KW - Proteins KW - Trifluoroacetic Acid KW - E5R8Z4G708 KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Base Sequence KW - Guinea Pigs KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Immunohistochemistry KW - Male KW - Anesthetics, Inhalation -- toxicity KW - Halothane -- toxicity KW - Proteins -- metabolism KW - Trifluoroacetic Acid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77057750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Halothane-induced+liver+injury+in+outbred+guinea+pigs%3A+role+of+trifluoroacetylated+protein+adducts+in+animal+susceptibility.&rft.au=Bourdi%2C+M%3BAmouzadeh%2C+H+R%3BRushmore%2C+T+H%3BMartin%2C+J+L%3BPohl%2C+L+R&rft.aulast=Bourdi&rft.aufirst=M&rft.date=2001-04-01&rft.volume=14&rft.issue=4&rft.spage=362&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of nonhuman primate models to improve gene transfer into haematopoietic stem cells. AN - 77052252; 11298853 AB - Primitive haematopoietic progenitor and stem cells (HSC) have been pursued as highly desirable targets for genetic therapy as technology allowing safe and controllable transfer of exogenous genes into eukaryotic cells was developed a decade ago. Retroviral vectors have been used for the majority of preclinical and clinical studies directed at these cells, because these vectors have a number of the necessary properties, including chromosomal integration, helper-free production systems, and lack of toxicity. Until recently, however, results with these vectors in clinical trials and large animal models indicated efficiency of gene transfer as a major hurdle to be overcome. We have focused on using the rhesus macaque autologous transplantation model to optimize gene transfer to primitive haematopoietic cells, and investigate questions regarding in vivo stem cell behaviour, in a system with proven predictive value for human haematopoiesis. By optimization of transduction conditions using standard vectors, gene transfer efficiency to primitive repopulating cells has reached the clinically relevant range of 5-20% long-term. Alternative vector systems, have also yielded promising results. We have also found that relatively simple manipulation of cell cycle status prior to reinfusion of marked cells results in significantly improved engraftment of transduced cells: this finding may have an impact particularly in the nonablative setting. The high level marking has permitted insertion site analysis and clonal tracking in vivo. Inverse PCR and/or a ligation-mediated PCR procedure have demonstrated that a large number of transduced clones (over 50) contribute to multiple lineages in vivo for up to at least 2 years post-transplantation. Thus far we have little evidence for rapid clonal succession or lineage-restricted engraftment of transduced cells. These and other advances should result in successful gene therapy for a variety of acquired and congenital disorders affecting HSCs and their progeny lineages. JF - Journal of internal medicine AU - Dunbar, C E AD - Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville Pike, Bethesda, MD, USA. dunbarc@nhlbi.nih.edu Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 329 EP - 338 VL - 249 IS - 4 SN - 0954-6820, 0954-6820 KW - Index Medicus KW - Animals KW - Humans KW - Genetic Vectors KW - Transgenes KW - Transduction, Genetic KW - Hematopoietic Stem Cell Mobilization KW - Gene Expression KW - Macaca mulatta KW - Models, Animal KW - Gene Transfer Techniques KW - Hematopoietic Stem Cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77052252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+internal+medicine&rft.atitle=The+use+of+nonhuman+primate+models+to+improve+gene+transfer+into+haematopoietic+stem+cells.&rft.au=Dunbar%2C+C+E&rft.aulast=Dunbar&rft.aufirst=C&rft.date=2001-04-01&rft.volume=249&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Journal+of+internal+medicine&rft.issn=09546820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial. AN - 77051937; 11297592 AB - Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS. JF - The Journal of clinical endocrinology and metabolism AU - Then Bergh, F AU - Kümpfel, T AU - Grasser, A AU - Rupprecht, R AU - Holsboer, F AU - Trenkwalder, C AD - Department of Neurology, Max Planck Institute of Psychiatry, 80804 Munich, Germany. thenberf@ninds.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1610 EP - 1615 VL - 86 IS - 4 SN - 0021-972X, 0021-972X KW - Adrenal Cortex Hormones KW - 0 KW - Antidepressive Agents KW - Glucocorticoids KW - Fluocortolone KW - 65VXC1MH0J KW - Moclobemide KW - PJ0Y7AZB63 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Reference Values KW - Double-Blind Method KW - Humans KW - Fluocortolone -- therapeutic use KW - Fluocortolone -- adverse effects KW - Adult KW - Disability Evaluation KW - Glucocorticoids -- adverse effects KW - Glucocorticoids -- therapeutic use KW - Male KW - Hydrocortisone -- blood KW - Female KW - Moclobemide -- therapeutic use KW - Adrenal Cortex Hormones -- therapeutic use KW - Moclobemide -- adverse effects KW - Multiple Sclerosis, Relapsing-Remitting -- physiopathology KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Pituitary-Adrenal System -- physiopathology KW - Antidepressive Agents -- therapeutic use KW - Antidepressive Agents -- adverse effects KW - Multiple Sclerosis, Relapsing-Remitting -- drug therapy KW - Adrenal Cortex Hormones -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77051937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Combined+treatment+with+corticosteroids+and+moclobemide+favors+normalization+of+hypothalamo-pituitary-adrenal+axis+dysregulation+in+relapsing-remitting+multiple+sclerosis%3A+a+randomized%2C+double+blind+trial.&rft.au=Then+Bergh%2C+F%3BK%C3%BCmpfel%2C+T%3BGrasser%2C+A%3BRupprecht%2C+R%3BHolsboer%2C+F%3BTrenkwalder%2C+C&rft.aulast=Then+Bergh&rft.aufirst=F&rft.date=2001-04-01&rft.volume=86&rft.issue=4&rft.spage=1610&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bladder cancer in Africa: update. AN - 77046846; 11301380 AB - Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation. Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative. Semin Oncol 28:174-178. Copyright 2001 by W.B. Saunders Company. JF - Seminars in oncology AU - el-Mawla, N G AU - el-Bolkainy, M N AU - Khaled, H M AD - Department of Medical Oncology, National Cancer Institute, Cairo, Egypt. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 174 EP - 178 VL - 28 IS - 2 SN - 0093-7754, 0093-7754 KW - Index Medicus KW - Survival Rate KW - Schistosomiasis -- epidemiology KW - Africa -- epidemiology KW - Humans KW - Egypt -- epidemiology KW - Schistosomiasis -- complications KW - Male KW - Female KW - Urinary Bladder Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- etiology KW - Urinary Bladder Neoplasms -- epidemiology KW - Urinary Bladder Neoplasms -- therapy KW - Developing Countries UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77046846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Bladder+cancer+in+Africa%3A+update.&rft.au=el-Mawla%2C+N+G%3Bel-Bolkainy%2C+M+N%3BKhaled%2C+H+M&rft.aulast=el-Mawla&rft.aufirst=N&rft.date=2001-04-01&rft.volume=28&rft.issue=2&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Executive Summary of the National Cancer Institute Workshop: Highlights and recommendations. AN - 77043355; 11295590 AB - Prostate cancer chemoprevention represents a relatively new and promising strategy for reducing the immense public health burden of this devastating cancer of men in the United States and Western societies. Chemoprevention is defined as the administration of agents (drugs, biologics, and natural products) that modulate (inhibit) one or more steps in the multistage carcinogenesis process culminating in invasive adenocarcinoma of the prostate. In 2000, there were an estimated 170,000 new cases of prostate cancer and 31,000 deaths in the United States. During the past decade, the National Cancer Institute (NCI) organized the chemoprevention research program and began testing the first generation of promising agents (eg, 4-(hydroxy)-fenretinide [4-HPR], difluoromethylornithine [DFMO], antiandrogens) in high-risk cohorts and launched the first-large scale US phase 3 primary prevention trial, known as Prostate Cancer Prevention Trial (PCPT-1), in 18,000 average-risk men (age more than 55 years and prostate-specific antigen [PSA] less than 3 ng/mL) treated for 7 years with finasteride or placebo. In the summer of 1998, the NCI Prostate Cancer Progress Review Group (PRG) Report to the director of NCI was published in response to the leadership of the prostate cancer advocacy community in conjunction with Congress. To further elucidate and address critical issues identified in this report and to develop a research agenda for the newly created Prostate and Urologic Cancer Research Group in the Division of Cancer Prevention at NCI, the NCI organized the workshop "New Clinical Trial Strategies for Prostate Cancer Chemoprevention." The major objectives were to promote understanding and cooperation among the NCI, US Food and Drug Administration (FDA), academia, pharmaceutical industry, and the public regarding new opportunities for clinical prevention trials for prostate cancer. The workshop was divided into three concurrent breakout panels and a fourth joint integrative panel. The workshop addressed multiple key areas identified in the PRG report in the following panels: (1) Molecular Targets and Promising Agents in Clinical Development; (2) Intermediate Endpoint Biomarkers for Prevention Trials; (3) High-Risk Study Populations for Prevention Trials, and (4) Preventive Clinical Trial Designs and Regulatory Issues. Expert panelists were drawn from leading academic, pharmaceutical, and government scientists in basic research and clinical investigation. Key pharmaceutical, biotechnology, academic, and National Institutes of Health scientists presented overviews of their new agents and products in clinical development (representing the next generation of promising agents). Senior FDA physicians from the Center for Drugs and Center for Biologics presented on current standards for new drug and biologic approval for chemoprevention efficacy. Some of the key topics included recent advances in the state of knowledge of promising agents in the clinic based on molecular targets as well as bottlenecks in drug development for pharmaceutical sponsors; strategic modulable biomarkers that can serve as primary endpoints in phase 1/2 trials to assess preventive efficacy; high-risk cohorts with precancer (high-grade prostatic intraepithelial neoplasia) and representative clinical trial designs that are ready for immediate translation into efficient prevention trials, such as Bayesian sequential monitoring for early assessment of biologic activity and factorial designs for assessment of multiagent combinations. Finally, each expert panel generated recommendations for areas of future research emphasizing opportunities and infrastructure needs. JF - Urology AU - Lieberman, R AU - Nelson, W G AU - Sakr, W A AU - Meyskens, F L AU - Klein, E A AU - Wilding, G AU - Partin, A W AU - Lee, J J AU - Lippman, S M Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 4 EP - 27 VL - 57 IS - 4 Suppl 1 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - Biomarkers, Tumor KW - Index Medicus KW - United States KW - Humans KW - Interinstitutional Relations KW - Clinical Trials as Topic KW - Drug Industry KW - United States Food and Drug Administration KW - Government KW - National Institutes of Health (U.S.) KW - Practice Guidelines as Topic KW - Middle Aged KW - Antineoplastic Agents -- therapeutic use KW - Male KW - Anticarcinogenic Agents -- therapeutic use KW - Prostatic Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77043355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Urology&rft.atitle=Executive+Summary+of+the+National+Cancer+Institute+Workshop%3A+Highlights+and+recommendations.&rft.au=Lieberman%2C+R%3BNelson%2C+W+G%3BSakr%2C+W+A%3BMeyskens%2C+F+L%3BKlein%2C+E+A%3BWilding%2C+G%3BPartin%2C+A+W%3BLee%2C+J+J%3BLippman%2C+S+M&rft.aulast=Lieberman&rft.aufirst=R&rft.date=2001-04-01&rft.volume=57&rft.issue=4+Suppl+1&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=Urology&rft.issn=1527-9995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons. AN - 77043331; 11298787 AB - We have recently demonstrated that embryonic E16 hippocampal neurons grown in cultures are unable to form fast synaptic connections unless treated with BDNF or NT-3. This experimental system offers an opportunity to define the roles of neurotrophins in processes leading to formation of functional synaptic connections. We have used ultrastructural and electrophysiological methods to explore the cellular locations underlying neurotrophin action on synaptic maturation. The rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs) evoked by hyperosmotic stimulation was 7-16-fold higher in neurotrophin-treated cells than in controls. In addition, the potent neurotransmitter-releasing drug alpha-latrotoxin was virtually ineffective in the control cells while it stimulated synaptic events in neurotrophin-treated cells. Likewise, the membrane-bound dye FM1-43 was taken up by terminals in neurotrophin-treated cultures five-fold more than in controls. Both the total number and the number of docked synaptic vesicles were increased by neurotrophin treatment. Activation of synaptic responses by neurotrophins occurred even when postsynaptic glutamate receptors and action potential discharges were pharmacologically blocked. These results are consistent with a presynaptic locus of action of neurotrophins to increase synaptic vesicle density which is critical for rapid synaptic transmission. They also suggest that neurotrophins can activate synapses in the absence of pre- and postsynaptic neuronal activity. JF - The European journal of neuroscience AU - Collin, C AU - Vicario-Abejon, C AU - Rubio, M E AU - Wenthold, R J AU - McKay, R D AU - Segal, M AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland 20892-4092, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1273 EP - 1282 VL - 13 IS - 7 SN - 0953-816X, 0953-816X KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Excitatory Amino Acid Antagonists KW - Neurotrophin 3 KW - Spider Venoms KW - Tetrodotoxin KW - 4368-28-9 KW - alpha-latrotoxin KW - 65988-34-3 KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Index Medicus KW - Action Potentials -- physiology KW - Animals KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Synaptic Vesicles -- ultrastructure KW - Action Potentials -- drug effects KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Excitatory Postsynaptic Potentials -- drug effects KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Cells, Cultured KW - Hippocampus -- cytology KW - Synaptic Vesicles -- physiology KW - Microscopy, Electron KW - Tetrodotoxin -- pharmacology KW - Spider Venoms -- pharmacology KW - Excitatory Postsynaptic Potentials -- physiology KW - Presynaptic Terminals -- ultrastructure KW - Neurotrophin 3 -- pharmacology KW - Presynaptic Terminals -- drug effects KW - Brain-Derived Neurotrophic Factor -- pharmacology KW - Neurons -- cytology KW - Neurons -- physiology KW - Presynaptic Terminals -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77043331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+European+journal+of+neuroscience&rft.atitle=Neurotrophins+act+at+presynaptic+terminals+to+activate+synapses+among+cultured+hippocampal+neurons.&rft.au=Collin%2C+C%3BVicario-Abejon%2C+C%3BRubio%2C+M+E%3BWenthold%2C+R+J%3BMcKay%2C+R+D%3BSegal%2C+M&rft.aulast=Collin&rft.aufirst=C&rft.date=2001-04-01&rft.volume=13&rft.issue=7&rft.spage=1273&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. AN - 77042006; 11296091 AB - SR141716, a recently developed CB1 cannabinoid receptor antagonist, blocks acute effects of Delta-9-tetrahydrocannabinol (THC) and other CB1 cannabinoid agonists in vitro and in animals. These findings suggest that CB1 receptors mediate many of the effects of marijuana, but this has not been evaluated in humans. Sixty-three healthy men with a history of marijuana use were randomly assigned to receive oral SR141716 or a placebo in an escalating dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64% THC) or placebo marijuana cigarette 2 hours later. Psychological effects associated with marijuana intoxication and heart rate were measured before and after antagonist and marijuana administration. Single oral doses of SR141716 produced a significant dose-dependent blockade of marijuana-induced subjective intoxication and tachycardia. The 90-mg dose produced 38% to 43% reductions in visual analog scale ratings of "How high do you feel now?" "How stoned on marijuana are you now?" and "How strong is the drug effect you feel now?" and produced a 59% reduction in heart rate. SR141716 alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or the area under the time x concentration curve. SR141716 was well tolerated by all subjects. SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana. JF - Archives of general psychiatry AU - Huestis, M A AU - Gorelick, D A AU - Heishman, S J AU - Preston, K L AU - Nelson, R A AU - Moolchan, E T AU - Frank, R A AD - National Institute on Drug Abuse Intramural Research Program, 5500 Nathan Shock Dr, Baltimore, MD 21224, USA. mhuestis@intra.nida.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 322 EP - 328 VL - 58 IS - 4 SN - 0003-990X, 0003-990X KW - Cannabinoids KW - 0 KW - Piperidines KW - Placebos KW - Pyrazoles KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Dronabinol KW - 7J8897W37S KW - rimonabant KW - RML78EN3XE KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Euphoria -- drug effects KW - Animals KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Tachycardia -- physiopathology KW - Euphoria -- physiology KW - Heart Rate -- drug effects KW - Adult KW - Heart Rate -- physiology KW - Tachycardia -- chemically induced KW - Male KW - Piperidines -- pharmacology KW - Pyrazoles -- pharmacology KW - Piperidines -- pharmacokinetics KW - Dronabinol -- blood KW - Marijuana Abuse -- psychology KW - Marijuana Abuse -- blood KW - Receptors, Drug -- antagonists & inhibitors KW - Pyrazoles -- pharmacokinetics KW - Marijuana Abuse -- physiopathology KW - Cannabinoids -- antagonists & inhibitors KW - Dronabinol -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77042006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Blockade+of+effects+of+smoked+marijuana+by+the+CB1-selective+cannabinoid+receptor+antagonist+SR141716.&rft.au=Huestis%2C+M+A%3BGorelick%2C+D+A%3BHeishman%2C+S+J%3BPreston%2C+K+L%3BNelson%2C+R+A%3BMoolchan%2C+E+T%3BFrank%2C+R+A&rft.aulast=Huestis&rft.aufirst=M&rft.date=2001-04-01&rft.volume=58&rft.issue=4&rft.spage=322&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Gen Psychiatry. 2001 Apr;58(4):330-1 [11296092] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-induced lupus associated with COL-3: report of 3 cases. AN - 77040142; 11295928 AB - Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduct of a phase 1 clinical trial for refractory metastatic cancer at the National Institutes of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus. Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer within 8 to 29 days of starting treatment. Two of 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up. COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed. JF - Archives of dermatology AU - Ghate, J V AU - Turner, M L AU - Rudek, M A AU - Figg, W D AU - Dahut, W AU - Dyer, V AU - Pluda, J M AU - Reed, E AD - Dermatology Branch, National Institutes of Health, Bldg 10, Room 12N238, Bethesda, MD 20892-1908, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 471 EP - 474 VL - 137 IS - 4 SN - 0003-987X, 0003-987X KW - Anti-Inflammatory Agents KW - 0 KW - Glucocorticoids KW - Matrix Metalloproteinase Inhibitors KW - Ointments KW - Protease Inhibitors KW - Tetracyclines KW - tetracycline CMT-3 KW - Clobetasol KW - ADN79D536H KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Prednisone -- therapeutic use KW - Humans KW - Anti-Inflammatory Agents -- therapeutic use KW - Aged KW - Anti-Inflammatory Agents -- administration & dosage KW - Clobetasol -- administration & dosage KW - Clobetasol -- analogs & derivatives KW - Follow-Up Studies KW - Middle Aged KW - Time Factors KW - Administration, Topical KW - Female KW - Male KW - Protease Inhibitors -- adverse effects KW - Tetracyclines -- adverse effects KW - Neoplasm Metastasis -- drug therapy KW - Lupus Erythematosus, Cutaneous -- drug therapy KW - Lupus Erythematosus, Cutaneous -- diagnosis KW - Lupus Erythematosus, Cutaneous -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77040142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+dermatology&rft.atitle=Drug-induced+lupus+associated+with+COL-3%3A+report+of+3+cases.&rft.au=Ghate%2C+J+V%3BTurner%2C+M+L%3BRudek%2C+M+A%3BFigg%2C+W+D%3BDahut%2C+W%3BDyer%2C+V%3BPluda%2C+J+M%3BReed%2C+E&rft.aulast=Ghate&rft.aufirst=J&rft.date=2001-04-01&rft.volume=137&rft.issue=4&rft.spage=471&rft.isbn=&rft.btitle=&rft.title=Archives+of+dermatology&rft.issn=0003987X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence databases and microarrays as tools for identifying prostate cancer biomarkers. AN - 77039324; 11295616 AB - Identification, acquisition, and assessment of molecular markers that could be adopted as surrogate endpoints for evaluating a response to prostate cancer intervention strategies is highly desirable. Recent advances in the fields of genomics and biotechnology have dramatically increased the quantity and accessibility of molecular information that is relevant to the study of prostate carcinogenesis. One major advance involves the construction of comprehensive databases that archive gene sequences and gene expression data. This information is in a format suitable for virtual queries designed to distinguish the molecular differences between normal and cancer cells. A second major advance uses robotic tools to construct microarrays comprising thousands of distinct genes expressed in prostate tissues. Such arrays offer a powerful approach for monitoring the expression of thousands of genes simultaneously and provide access for techniques designed to assess patterns or "fingerprints" of gene expression that may ultimately be used as signatures of response to therapeutic intervention. JF - Urology AU - Grouse, L H AU - Munson, P J AU - Nelson, P S AD - Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 154 EP - 159 VL - 57 IS - 4 Suppl 1 KW - Biomarkers, Tumor KW - 0 KW - DNA, Complementary KW - Genetic Markers KW - Index Medicus KW - Base Sequence KW - DNA, Complementary -- genetics KW - Humans KW - Male KW - Biomarkers, Tumor -- genetics KW - Precancerous Conditions -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Precancerous Conditions -- prevention & control KW - Databases, Factual KW - Prostatic Neoplasms -- genetics KW - Prostatic Neoplasms -- prevention & control KW - Gene Expression Profiling -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77039324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urology&rft.atitle=Sequence+databases+and+microarrays+as+tools+for+identifying+prostate+cancer+biomarkers.&rft.au=Grouse%2C+L+H%3BMunson%2C+P+J%3BNelson%2C+P+S&rft.aulast=Grouse&rft.aufirst=L&rft.date=2001-04-01&rft.volume=57&rft.issue=4+Suppl+1&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=Urology&rft.issn=1527-9995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agents, biomarkers, and cohorts for chemopreventive agent development in prostate cancer. AN - 77039295; 11295594 AB - Chemoprevention is the use of agents to slow progression of, reverse, or inhibit carcinogenesis thereby lowering the risk of developing invasive or clinically significant disease. With its long latency, high incidence and significant morbidity and mortality, prostate cancer is a relevant target for chemoprevention. Developing rational chemopreventive strategies for prostate cancer requires well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer. Chemopreventive agent requirements are experimental or epidemiologic data showing efficacy, safety on chronic administration, and a mechanistic rationale for activity. Current promising agents include antiandrogens and antiestrogens; steroid aromatase inhibitors; retinoids and their modulators; 5alpha-reductase inhibitors; vitamins D, E, and analogs; selenium compounds; carotenoids; soy isoflavones; dehydroepiandrostenedione and analogs; 2-difluoromethylornithine; lipoxygenase inhibitors; apoptosis inducers; and nonsteroidal anti-inflammatory drugs. Identifying biomarkers and validating them as surrogate endpoints for cancer incidence are critical for prostate chemoprevention trials. Potentially useful biomarkers for prostate chemoprevention are associated with histologic, proliferative, differentiation-related, biochemical, and genetic/regulatory features of prostatic disease. In that the prostate is not easily visualized, critical issues also include adequacy and consistency of tissue sampling. Various drugs for the chemoprevention of prostate cancer are now under evaluation in phase 1, 2, and 3 clinical trials. Cohort selection should be based on various patient characteristics (stage of the disease, previous cancers or premalignant lesions, or high risk factors) and should be conducted within the context of standard treatment. JF - Urology AU - Kelloff, G J AU - Lieberman, R AU - Steele, V E AU - Boone, C W AU - Lubet, R A AU - Kopelovich, L AU - Malone, W A AU - Crowell, J A AU - Higley, H R AU - Sigman, C C AD - National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland, USA. kelloffg@.mail.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 46 EP - 51 VL - 57 IS - 4 Suppl 1 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers KW - Index Medicus KW - Models, Animal KW - Risk Factors KW - Humans KW - Cohort Studies KW - Clinical Trials as Topic KW - Patient Selection KW - Male KW - Prostatic Neoplasms -- epidemiology KW - Anticarcinogenic Agents -- therapeutic use KW - Prostatic Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77039295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urology&rft.atitle=Agents%2C+biomarkers%2C+and+cohorts+for+chemopreventive+agent+development+in+prostate+cancer.&rft.au=Kelloff%2C+G+J%3BLieberman%2C+R%3BSteele%2C+V+E%3BBoone%2C+C+W%3BLubet%2C+R+A%3BKopelovich%2C+L%3BMalone%2C+W+A%3BCrowell%2C+J+A%3BHigley%2C+H+R%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=2001-04-01&rft.volume=57&rft.issue=4+Suppl+1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Urology&rft.issn=1527-9995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue inhibitor of metalloproteinase-1 alters the tumorigenicity of Burkitt's lymphoma via divergent effects on tumor growth and angiogenesis. AN - 77035697; 11290537 AB - Epstein-Barr virus (EBV)-positive Burkitt's lymphoma cells and EBV-infected B cells elicit humoral factors that inhibit tumor-induced angiogenesis, resulting in tumor necrosis and regression. Of the chemokine factors identified in association with this growth behavior, none have induced complete tumor regression. We have previously identified tissue inhibitors of metalloproteinase (TIMP)-1 in various B cell lymphoma cell lines. Here we show that induction of TIMP-1 expression in an EBV-negative Burkitt's lymphoma cell line results in a biphasic, in vivo tumor growth pattern in the nude mouse that is essentially identical to EBV-positive Burkitt's lymphoma cell lines. The initial effect of TIMP-1 is to enhance tumor growth, consistent with the reported anti-apoptotic effect of TIMP-1 on B cell growth. Tumor necrosis and regression then follow the initial period of rapid, increased tumor growth. Only microscopic foci of residual, proliferating tumor cells are observed on biopsy of the tumor site. This latter effect is mediated by TIMP-1 inhibition of an angiogenic response within the developing tumor mass, as demonstrated by immunostaining and microvessel counts. These findings suggest that TIMP-1 is an important mediator of the in vivo growth properties of EBV-positive Burkitt's lymphoma. JF - The American journal of pathology AU - Guedez, L AU - McMarlin, A J AU - Kingma, D W AU - Bennett, T A AU - Stetler-Stevenson, M AU - Stetler-Stevenson, W G AD - National Institutes of Health, National Cancer Institute, Extracellular Matrix Section, Laboratory of Pathology, Division of Clinical Sciences, Bethesda, MD 20892, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1207 EP - 1215 VL - 158 IS - 4 SN - 0002-9440, 0002-9440 KW - Antineoplastic Agents KW - 0 KW - Tissue Inhibitor of Metalloproteinase-1 KW - Abridged Index Medicus KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Necrosis KW - Tumor Cells, Cultured KW - Cell Division -- drug effects KW - Carcinogenicity Tests KW - Mice, Nude KW - Mice KW - Female KW - Neovascularization, Pathologic -- physiopathology KW - Burkitt Lymphoma -- physiopathology KW - Tissue Inhibitor of Metalloproteinase-1 -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Burkitt Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77035697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Tissue+inhibitor+of+metalloproteinase-1+alters+the+tumorigenicity+of+Burkitt%27s+lymphoma+via+divergent+effects+on+tumor+growth+and+angiogenesis.&rft.au=Guedez%2C+L%3BMcMarlin%2C+A+J%3BKingma%2C+D+W%3BBennett%2C+T+A%3BStetler-Stevenson%2C+M%3BStetler-Stevenson%2C+W+G&rft.aulast=Guedez&rft.aufirst=L&rft.date=2001-04-01&rft.volume=158&rft.issue=4&rft.spage=1207&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer. 1999 Nov 15;86(10):1929-35 [10570415] Cancer Res. 1999 Dec 15;59(24):6267-75 [10626822] Cell. 2000 Jan 7;100(1):57-70 [10647931] Int J Cancer. 2000 Mar 20;89(2):118-21 [10756061] Anticancer Res. 2000 Mar-Apr;20(2B):1311-6 [10810441] Fertil Steril. 2000 Jul;74(1):107-12 [10899506] Oncogene. 2000 Jul 20;19(31):3477-86 [10918606] N Engl J Med. 2000 Aug 17;343(7):481-92 [10944566] Science. 2000 Aug 18;289(5482):1202-6 [10947989] Clin Cancer Res. 2000 Nov;6(11):4292-9 [11106246] Blood. 2001 Mar 15;97(6):1796-802 [11238122] Int J Cancer. 1987 Jan 15;39(1):25-9 [3025109] Science. 1989 Feb 17;243(4893):947-50 [2465572] Adv Cancer Res. 1990;55:133-270 [2166998] Biochem Biophys Res Commun. 1990 Sep 28;171(3):1264-71 [1699524] J Natl Cancer Inst. 1991 Jun 5;83(11):775-9 [1645772] Cancer Res. 1992 Feb 1;52(3):701-8 [1732058] J Cell Biol. 1992 Aug;118(3):727-39 [1639854] J Cell Physiol. 1993 Aug;156(2):235-46 [8344982] J Cell Physiol. 1993 Nov;157(2):351-8 [7693724] Blood. 1994 Feb 1;83(3):776-84 [8298139] J Cell Physiol. 1994 Jul;160(1):194-202 [7517405] Leuk Lymphoma. 1995 Oct;19(3-4):267-76 [8535218] Am J Surg Pathol. 1996 Jan;20(1):103-11 [8540601] Cell. 1996 Aug 9;86(3):353-64 [8756718] In Vivo. 1996 Mar-Apr;10(2):137-44 [8744792] FEBS Lett. 1996 Oct 28;396(1):103-7 [8906876] Anal Biochem. 1997 Jan 1;244(1):161-6 [9025922] Crit Rev Oncog. 1996;7(3-4):205-25 [9258603] Blood. 1997 Sep 1;90(5):1993-2000 [9292534] Blood. 1997 Nov 15;90(10):4099-105 [9354680] Curr Opin Oncol. 1997 Nov;9(6):584-9 [9370081] Blood. 1998 Apr 1;91(7):2491-500 [9516150] Cell. 1998 May 1;93(3):411-22 [9590175] Blood. 1998 Aug 15;92(4):1342-9 [9694723] J Clin Invest. 1998 Dec 1;102(11):2002-10 [9835626] J Surg Res. 1999 Apr;82(2):156-62 [10090824] J Cell Sci. 1999 May;112 ( Pt 10):1599-609 [10212153] Genes Dev. 1999 Jun 1;13(11):1382-97 [10364156] Cell. 1999 Jul 23;98(2):137-46 [10428026] J Cell Biol. 1999 Aug 23;146(4):881-92 [10459021] Cell. 1999 Oct 1;99(1):81-92 [10520996] Comment In: Am J Pathol. 2001 Apr;158(4):1185-90 [11290534] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel role for a Saccharomyces cerevisiae nucleoporin, Nup170p, in chromosome segregation. AN - 77033952; 11290711 AB - We determined that a mutation in the nucleoporin gene NUP170 leads to defects in chromosome transmission fidelity (ctf) and kinetochore integrity in Saccharomyces cerevisiae. A ctf mutant strain, termed s141, shows a transcription readthrough phenotype and stabilizes a dicentric chromosome fragment in two assays for kinetochore integrity. Previously, these assays led to the identification of two essential kinetochore components, Ctf13p and Ctf14p. Thus, s141 represents another ctf mutant involved in the maintenance of kinetochore integrity. We cloned and mapped the gene complementing the ctf mutation of s141 and showed that it is identical to the S. cerevisiae NUP170 gene. A deletion strain of NUP170 (nup170 Delta::HIS3) has a Ctf(-) phenotype similar to the s141 mutant (nup170-141) and also exhibits a kinetochore integrity defect. We identified a second nucleoporin, NUP157, a homologue of NUP170, as a suppressor of the Ctf(-) phenotype of nup170-141 and nup170 Delta::HIS3 strains. However, a deletion of NUP157 or several other nucleoporins did not affect chromosome segregation. Our data suggest that NUP170 encodes a specialized nucleoporin with a unique role in chromosome segregation and possibly kinetochore function. JF - Genetics AU - Kerscher, O AU - Hieter, P AU - Winey, M AU - Basrai, M A AD - Department of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1543 EP - 1553 VL - 157 IS - 4 SN - 0016-6731, 0016-6731 KW - CBF2 protein, S cerevisiae KW - 0 KW - CTF13 protein, S cerevisiae KW - DNA, Fungal KW - DNA-Binding Proteins KW - Fungal Proteins KW - Membrane Proteins KW - NUP157 protein, S cerevisiae KW - NUP170 protein, S cerevisiae KW - Nuclear Pore Complex Proteins KW - Nuclear Proteins KW - Saccharomyces cerevisiae Proteins KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Kinetochores KW - Nuclear Envelope -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - DNA, Fungal -- metabolism KW - Mutagenesis KW - DNA-Binding Proteins -- metabolism KW - Fungal Proteins -- physiology KW - Fungal Proteins -- metabolism KW - Nuclear Proteins -- genetics KW - Membrane Proteins -- metabolism KW - Chromosome Segregation KW - Membrane Proteins -- genetics KW - Fungal Proteins -- genetics KW - Nuclear Proteins -- metabolism KW - Nuclear Proteins -- physiology KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77033952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Novel+role+for+a+Saccharomyces+cerevisiae+nucleoporin%2C+Nup170p%2C+in+chromosome+segregation.&rft.au=Kerscher%2C+O%3BHieter%2C+P%3BWiney%2C+M%3BBasrai%2C+M+A&rft.aulast=Kerscher&rft.aufirst=O&rft.date=2001-04-01&rft.volume=157&rft.issue=4&rft.spage=1543&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3224-9 [10716708] Mol Cell. 1999 Sep;4(3):445-50 [10518226] J Cell Sci. 2000 Jun;113 ( Pt 11):1903-12 [10806101] Science. 2000 May 26;288(5470):1374-7 [10827939] J Cell Biol. 2000 May 29;149(5):1027-38 [10831607] Proc Natl Acad Sci U S A. 1983 Jan;80(1):228-32 [6337372] Genetics. 1984 Feb;106(2):207-26 [6365688] Cell. 1985 Feb;40(2):381-92 [3967296] Cell. 1986 Jan 17;44(1):65-76 [3510081] Genetics. 1989 May;122(1):19-27 [2659436] Genetics. 1990 Feb;124(2):237-49 [2407610] EMBO J. 1990 Dec;9(13):4347-58 [2265610] Cell. 1993 May 21;73(4):761-74 [8500169] Mol Cell Biol. 1993 Aug;13(8):4691-702 [8336709] Nucleic Acids Res. 1993 Jul 11;21(14):3329-30 [8341614] J Cell Biol. 1993 Aug;122(4):743-51 [8349727] Genetics. 1994 Dec;138(4):1067-79 [7896091] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7647-51 [7644471] Mol Cell Biol. 1996 May;16(5):2025-36 [8628268] Mol Cell Biol. 1996 Jun;16(6):2838-47 [8649393] Cell. 1996 Jul 26;86(2):275-85 [8706132] J Cell Biol. 1997 Mar 24;136(6):1185-99 [9087436] Nucleic Acids Res. 2000 Jan 1;28(1):73-6 [10592185] Annu Rev Cell Dev Biol. 1999;15:607-60 [10611974] Cell. 1999 Dec 23;99(7):677-90 [10619422] Nature. 2000 Jan 6;403(6765):108-12 [10638763] Nature. 2000 Feb 10;403(6770):623-7 [10688190] J Cell Biol. 2000 Feb 21;148(4):635-51 [10684247] Mol Gen Genet. 2000 Feb;263(1):60-72 [10732674] Genes Dev. 1997 Dec 15;11(24):3401-12 [9407032] Annu Rev Genet. 1997;31:277-313 [9442897] Mol Cell Biol. 1998 Feb;18(2):1115-24 [9448009] Yeast. 1998 Jan 30;14(2):115-32 [9483801] J Cell Biol. 1998 Sep 7;142(5):1195-207 [9732281] J Cell Biol. 1998 Dec 28;143(7):1789-800 [9864355] J Cell Biol. 1998 Dec 28;143(7):1813-30 [9864357] Annu Rev Genet. 1998;32:307-37 [9928483] Genes Dev. 1999 Feb 1;13(3):307-19 [9990855] J Cell Biol. 1999 Mar 8;144(5):839-55 [10085285] J Cell Biol. 1999 Apr 5;145(1):15-28 [10189365] Genomics. 1999 Apr 1;57(1):144-51 [10191094] Curr Opin Cell Biol. 1999 Apr;11(2):241-7 [10209150] Mol Biol Cell. 1999 Jul;10(7):2393-406 [10397772] Mol Cell. 1999 Jul;4(1):21-33 [10445024] Nucleic Acids Res. 1999 Aug 1;27(15):3001-8 [10454593] Genes Dev. 1999 Aug 15;13(16):2118-33 [10465789] Genetics. 1999 Oct;153(2):799-812 [10511559] Curr Opin Cell Biol. 2000 Jun;12(3):361-71 [10801463] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Household solvent exposures and childhood acute lymphoblastic leukemia. AN - 77030166; 11291366 AB - This study explored the risk of childhood acute lymphoblastic leukemia (ALL) associated with participation by household members in hobbies or other home projects involving organic solvents. Participants in this case-control study were 640 subjects with ALL and 640 matched controls. Childhood ALL was associated with frequent (> 4 times/month) exposure to model building (odds ratio [OR] = 1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes painted extensively (> 4 rooms) in the year before the children's birth. In this exploratory study, substantial participation by household members in some common household activities that involve organic solvents was associated with elevated risks of childhood ALL. JF - American journal of public health AU - Freedman, D M AU - Stewart, P AU - Kleinerman, R A AU - Wacholder, S AU - Hatch, E E AU - Tarone, R E AU - Robison, L L AU - Linet, M S AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza-South, Room 7087, 6120 Executive Blvd, Bethesda, MD 20892-7238, USA. mf101e@nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 564 EP - 567 VL - 91 IS - 4 SN - 0090-0036, 0090-0036 KW - Solvents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Humans KW - Data Collection KW - Child KW - United States -- epidemiology KW - Male KW - Female KW - Risk Assessment KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- chemically induced KW - Household Products -- adverse effects KW - Environmental Exposure KW - Solvents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77030166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=Household+solvent+exposures+and+childhood+acute+lymphoblastic+leukemia.&rft.au=Freedman%2C+D+M%3BStewart%2C+P%3BKleinerman%2C+R+A%3BWacholder%2C+S%3BHatch%2C+E+E%3BTarone%2C+R+E%3BRobison%2C+L+L%3BLinet%2C+M+S&rft.aulast=Freedman&rft.aufirst=D&rft.date=2001-04-01&rft.volume=91&rft.issue=4&rft.spage=564&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Epidemiol. 1984 Jul;120(1):164-6 [6741917] Scand J Work Environ Health. 1983 Jun;9(3):273-81 [6612269] Am J Hematol. 1985 Sep;20(1):89-90 [3861092] J Natl Cancer Inst. 1987 Jul;79(1):39-46 [3474448] J Natl Cancer Inst. 1987 Aug;79(2):233-8 [3474455] Cancer Res. 1989 Jul 15;49(14):4030-7 [2736544] BMJ. 1991 Mar 23;302(6778):681-7 [2021741] Cancer Causes Control. 1992 Mar;3(2):161-9 [1562706] Environ Health Perspect. 1991 Nov;95:7-13 [1821381] Bull Environ Contam Toxicol. 1993 Oct;51(4):501-7 [8400651] Arch Environ Health. 1996 May-Jun;51(3):242-4 [8687246] Crit Rev Toxicol. 1996 May;26(3):261-307 [8726164] Epidemiology. 1997 Sep;8(5):575-83 [9270962] Cancer Causes Control. 1997 May;8(3):406-19 [9498902] Epidemiology. 1998 May;9(3):234-45 [9583414] Environ Health Perspect. 1998 Jun;106 Suppl 3:909-25 [9646055] Cancer Epidemiol Biomarkers Prev. 1999 Sep;8(9):783-91 [10498397] Am J Epidemiol. 1985 Feb;121(2):216-24 [3860001] J Epidemiol Community Health. 1981 Mar;35(1):11-5 [7264527] JAMA. 1976 Jan 26;235(4):398-401 [946084] Br J Prev Soc Med. 1974 May;28(2):98-100 [4853418] Comment In: Am J Public Health. 2001 Apr;91(4):562-3 [11291365] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secreted Frizzled-related proteins can regulate metanephric development. AN - 77029251; 11287180 AB - Wnt-4 signaling plays a critical role in kidney development and is associated with the epithelial conversion of the metanephric mesenchyme. Furthermore, secreted Frizzled-related proteins (sFRPs) that can bind Wnts are normally expressed in the developing metanephros, and function in other systems as modulators of Wnt signaling. sfrp-1 is distributed throughout the medullary and cortical stroma in the metanephros, but is absent from condensed mesenchyme and primitive tubular epithelia of the developing nephron where wnt-4 is highly expressed. In contrast, sfrp-2 is expressed in primitive tubules. To determine their role in kidney development, recombinant sFRP-1, sFRP-2 or combinations of both were applied to cultures of 13-dpc rat metanephroi. Both tubule formation and bud branching were markedly inhibited by sFRP-1, but concurrent sFRP-2 treatment restored some tubular differentiation and bud branching. sFRP-2 itself showed no effect on cultures of metanephroi. In cultures of isolated, induced rat metanephric mesenchymes, sFRP-1 blocked events associated with epithelial conversion (tubulogenesis and expression of lim-1, sfrp-2 and E-cadherin); however, it had no demonstrable effect on early events (compaction of mesenchyme and expression of wt1). As shown herein, sFRP-1 binds Wnt-4 with considerable avidity and inhibits the DNA-binding activity of TCF, an effector of Wnt signaling, while sFRP-2 had no effect on TCF activation. These observations suggest that sFRP-1 and sFRP-2 compete locally to regulate Wnt signaling during renal organogenesis. The antagonistic effect of sFRP-1 may be important either in preventing inappropriate development within differentiated areas of the medulla or in maintaining a population of cortical blastemal cells to facilitate further renal expansion. On the other hand, sFRP-2 might promote tubule formation by permitting Wnt-4 signaling in the presence of sFRP-1. JF - Mechanisms of development AU - Yoshino, K AU - Rubin, J S AU - Higinbotham, K G AU - Uren, A AU - Anest, V AU - Plisov, S Y AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, Building 538/Room 205E, National Cancer Institute, Frederick, MD 21702, USA. yoshino@mail.ncifcrf.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 45 EP - 55 VL - 102 IS - 1-2 SN - 0925-4773, 0925-4773 KW - Cadherins KW - 0 KW - Frizzled Receptors KW - Homeodomain Proteins KW - LIM-Homeodomain Proteins KW - Lhx1 protein, mouse KW - Lhx1 protein, rat KW - Membrane Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - Recombinant Proteins KW - Sfrp2 protein, mouse KW - Transcription Factors KW - Wnt Proteins KW - Wnt4 Protein KW - Wnt4 protein, mouse KW - Wnt4 protein, rat KW - frizzled related protein-1 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Homeodomain Proteins -- biosynthesis KW - Cell Nucleus -- metabolism KW - Kidney -- embryology KW - Rats KW - In Situ Hybridization KW - Recombinant Proteins -- metabolism KW - Enzyme-Linked Immunosorbent Assay KW - Time Factors KW - Signal Transduction KW - Cadherins -- biosynthesis KW - Immunoblotting KW - Protein Biosynthesis KW - Dose-Response Relationship, Drug KW - DNA -- metabolism KW - Cell Differentiation KW - Mice KW - Kidney Tubules -- embryology KW - Protein Binding KW - Nephrons -- embryology KW - Cells, Cultured KW - Epithelium -- metabolism KW - Mesoderm -- metabolism KW - Immunohistochemistry KW - Proto-Oncogene Proteins -- physiology KW - Proteins -- physiology KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77029251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mechanisms+of+development&rft.atitle=Secreted+Frizzled-related+proteins+can+regulate+metanephric+development.&rft.au=Yoshino%2C+K%3BRubin%2C+J+S%3BHiginbotham%2C+K+G%3BUren%2C+A%3BAnest%2C+V%3BPlisov%2C+S+Y%3BPerantoni%2C+A+O&rft.aulast=Yoshino&rft.aufirst=K&rft.date=2001-04-01&rft.volume=102&rft.issue=1-2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+development&rft.issn=09254773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of Snapin by PKA modulates its interaction with the SNARE complex. AN - 77025321; 11283605 AB - cAMP-dependent protein kinase A (PKA) can modulate synaptic transmission by acting directly on unknown targets in the neurotransmitter secretory machinery. Here we identify Snapin, a protein of relative molecular mass 15,000 that is implicated in neurotransmission by binding to SNAP-25, as a possible target. Deletion mutation and site-directed mutagenetic experiments pinpoint the phosphorylation site to serine 50. PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation and enhances the association of synaptotagmin with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Furthermore, treatment of rat hippocampal slices with nonhydrolysable cAMP analogue induces in vivo phosphorylation of Snapin and enhances the interaction of both Snapin and synaptotagmin with the SNARE complex. In adrenal chromaffin cells, overexpression of the Snapin S50D mutant leads to an increase in the number of release-competent vesicles. Our results indicate that Snapin may be a PKA target for modulating transmitter release through the cAMP-dependent signal-transduction pathway. JF - Nature cell biology AU - Chheda, M G AU - Ashery, U AU - Thakur, P AU - Rettig, J AU - Sheng, Z H AD - Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Drive, Bethesda, Maryland 20892-4154, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 331 EP - 338 VL - 3 IS - 4 SN - 1465-7392, 1465-7392 KW - Calcium-Binding Proteins KW - 0 KW - Carrier Proteins KW - Membrane Glycoproteins KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Recombinant Fusion Proteins KW - SNARE Proteins KW - Snap25 protein, rat KW - Snapap protein, rat KW - Synaptosomal-Associated Protein 25 KW - Vesicular Transport Proteins KW - Synaptotagmins KW - 134193-27-4 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Recombinant Fusion Proteins -- genetics KW - Chromosome Mapping KW - Male KW - Binding Sites KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Carrier Proteins -- metabolism KW - Membrane Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Membrane Proteins -- genetics KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77025321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+cell+biology&rft.atitle=Phosphorylation+of+Snapin+by+PKA+modulates+its+interaction+with+the+SNARE+complex.&rft.au=Chheda%2C+M+G%3BAshery%2C+U%3BThakur%2C+P%3BRettig%2C+J%3BSheng%2C+Z+H&rft.aulast=Chheda&rft.aufirst=M&rft.date=2001-04-01&rft.volume=3&rft.issue=4&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Nature+cell+biology&rft.issn=14657392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural similarities between glutamate receptor channels and K(+) channels examined by scanning mutagenesis. AN - 77013314; 11279254 AB - The pores of glutamate receptors and K(+) channels share sequence homology, suggesting a conserved secondary structure. Scanning mutagenesis with substitution of alanine and tryptophan in GluR6 channels was performed based on the structure of KcsA. Our assay used disruption of voltage-dependent polyamine block to test for changes in the packing of pore-forming regions. Alanine scanning from D567 to R603 revealed reduced rectification resulting from channel block in two regions. A periodic pattern from F575 to M589 aligned with the pore helix in KcsA, whereas a cluster of sensitive positions around Q590, a site regulated by RNA editing, mapped to the selectivity filter in KcsA. Tryptophan scanning from D567 to R603 revealed similar patterns, but with a complete disruption of spermine block for 7 out of the 37 positions and a pM dissociation constant for Q590W. Molecular modeling with KcsA coordinates showed that GluR6 pore helix mutants disrupting polyamine block pack against M1 and M2, and are not exposed in the ion channel pore. In the selectivity filter, tryptophan creates an aromatic cage consistent with the pM dissociation constant for Q590W. A scan with glutamate substitution was used to map the cytoplasmic entrance to the pore based on charge neutralization experiments, which established that E594 was uniquely required for high affinity polyamine block. In E594Q mutants, introduction of glutamate at positions S593-L600 restored polyamine block at positions corresponding to surface-exposed residues in KcsA. Our results reinforce proposals that the pore region of glutamate receptors contains a helix and pore loop analogous to that found in K(+) channels. At the cytoplasmic entrance of the channel, a negatively charged amino acid, located in an extended loop with solvent-exposed side chains, is required for high affinity polyamine block and probably attracts cations via a through space electrostatic mechanism. JF - The Journal of general physiology AU - Panchenko, V A AU - Glasser, C R AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 345 EP - 360 VL - 117 IS - 4 SN - 0022-1295, 0022-1295 KW - Bacterial Proteins KW - 0 KW - Gluk2 kainate receptor KW - Polyamines KW - Potassium Channels KW - Receptors, Glutamate KW - Receptors, Kainic Acid KW - glutamate receptor type D KW - prokaryotic potassium channel KW - Tryptophan KW - 8DUH1N11BX KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Crystallization KW - Animals KW - Protein Structure, Secondary KW - Humans KW - Receptors, Glutamate -- metabolism KW - Membrane Potentials -- physiology KW - Mutagenesis -- physiology KW - Oocytes -- physiology KW - Receptors, Glutamate -- chemistry KW - Xenopus laevis KW - Receptors, Glutamate -- genetics KW - Polyamines -- pharmacology KW - Patch-Clamp Techniques KW - Kidney -- cytology KW - Molecular Sequence Data KW - Alanine -- genetics KW - Models, Chemical KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Cell Line KW - Tryptophan -- genetics KW - Receptors, Kainic Acid -- chemistry KW - Ion Channel Gating -- physiology KW - Potassium Channels -- metabolism KW - Potassium Channels -- chemistry KW - Receptors, Kainic Acid -- metabolism KW - Potassium Channels -- genetics KW - Receptors, Kainic Acid -- genetics KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77013314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+physiology&rft.atitle=Structural+similarities+between+glutamate+receptor+channels+and+K%28%2B%29+channels+examined+by+scanning+mutagenesis.&rft.au=Panchenko%2C+V+A%3BGlasser%2C+C+R%3BMayer%2C+M+L&rft.aulast=Panchenko&rft.aufirst=V&rft.date=2001-04-01&rft.volume=117&rft.issue=4&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+physiology&rft.issn=00221295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Physiol. 2000 Jun;115(6):799-814 [10828252] J Gen Physiol. 2000 Jun;115(6):783-98 [10828251] Nature. 1969 Mar 1;221(5183):844-6 [5765058] Science. 1990 Aug 3;249(4968):556-60 [2166337] J Physiol. 1990 Sep;428:313-31 [2172523] Nature. 1991 Jun 27;351(6329):745-8 [1648177] Neuron. 1992 Mar;8(3):483-91 [1550673] FEBS Lett. 1992 Jul 28;307(2):139-43 [1322826] Neuron. 1993 Dec;11(6):1069-82 [7506043] J Biol Chem. 1994 Jan 14;269(2):1332-9 [8288598] Pflugers Arch. 1994 Mar;426(5):453-8 [7517034] Biophys J. 1994 Apr;66(4):1061-7 [8038378] Science. 1995 Apr 14;268(5208):304-7 [7716526] Neuron. 1995 May;14(5):889-92 [7538310] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4882-6 [7761417] Trends Neurosci. 1995 Apr;18(4):161-8 [7539962] Neuron. 1995 Aug;15(2):453-62 [7646897] J Physiol. 1995 Jun 1;485 ( Pt 2):403-18 [7666365] Annu Rev Biochem. 1995;64:493-531 [7574491] EMBO J. 1995 Nov 1;14(21):5170-8 [7489706] Neuron. 1996 Aug;17(2):343-52 [8780657] Neuron. 1996 Feb;16(2):399-406 [8789954] Annu Rev Neurosci. 1996;19:235-63 [8833443] J Physiol. 1996 Oct 1;496 ( Pt 1):165-73 [8910205] J Physiol. 1997 Aug 1;502 ( Pt 3):575-89 [9279810] Mol Pharmacol. 1997 Oct;52(4):701-13 [9380034] Science. 1998 Apr 3;280(5360):69-77 [9525859] Science. 1998 Apr 3;280(5360):106-9 [9525854] Mol Pharmacol. 1998 May;53(5):933-41 [9584221] J Gen Physiol. 1998 Aug;112(2):243-57 [9689030] J Gen Physiol. 1998 Sep;112(3):351-63 [9725894] J Neurosci. 1998 Oct 15;18(20):8175-85 [9763464] Nature. 1998 Oct 29;395(6705):913-7 [9804426] Neuropharmacology. 1998 Oct-Nov;37(10-11):1381-91 [9849673] J Neurosci. 1999 Feb 1;19(3):916-27 [9920655] J Gen Physiol. 1999 Mar;113(3):415-23 [10051517] Science. 1999 Jul 2;285(5424):100-2 [10390357] Curr Opin Neurobiol. 1999 Jun;9(3):267-73 [10395571] Ann N Y Acad Sci. 1999 Apr 30;868:741-64 [10414361] J Physiol. 1999 Oct 15;520 Pt 2:337-57 [10523404] J Gen Physiol. 2000 Jan;115(1):33-50 [10613917] J Gen Physiol. 2000 Jan;115(1):51-8 [10613918] Nature. 1999 Dec 16;402(6763):817-21 [10617203] Neuron. 2000 Feb;25(2):411-23 [10719895] Neuron. 2000 Oct;28(1):165-81 [11086992] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide. AN - 77012379; 11279278 AB - The tumor suppressor protein p53 is essential for neuronal death in several experimental settings and may participate in human neurodegenerative disorders. Based upon recent studies characterizing chemical inhibitors of p53 in preclinical studies in the cancer therapy field, we synthesized the compound pifithrin-alpha and evaluated its potential neuroprotective properties in experimental models relevant to the pathogenesis of stroke and neurodegenerative disorders. Pifithrin-alpha protected neurons against apoptosis induced by DNA-damaging agents, amyloid beta-peptide and glutamate. Protection by pifithrin-alpha was correlated with decreased p53 DNA-binding activity, decreased expression of the p53 target gene BAX and suppression of mitochondrial dysfunction and caspase activation. Mice given pifithrin-alpha exhibited increased resistance of cortical and striatal neurons to focal ischemic injury and of hippocampal neurons to excitotoxic damage. These preclinical studies demonstrate the efficacy of a p53 inhibitor in models of stroke and neurodegenerative disorders, and suggest that drugs that inhibit p53 may reduce the extent of brain damage in related human neurodegenerative conditions. JF - Journal of neurochemistry AU - Culmsee, C AU - Zhu, X AU - Yu, Q S AU - Chan, S L AU - Camandola, S AU - Guo, Z AU - Greig, N H AU - Mattson, M P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore 21224, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 220 EP - 228 VL - 77 IS - 1 SN - 0022-3042, 0022-3042 KW - Amyloid beta-Peptides KW - 0 KW - Antineoplastic Agents KW - Benzothiazoles KW - Prodrugs KW - Thiazoles KW - Tumor Suppressor Protein p53 KW - Toluene KW - 3FPU23BG52 KW - Glutamic Acid KW - 3KX376GY7L KW - DNA KW - 9007-49-2 KW - pifithrin KW - D213B92S1Y KW - CASP3 protein, human KW - EC 3.4.22.- KW - Casp3 protein, mouse KW - Casp3 protein, rat KW - Caspase 3 KW - Caspases KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - DNA -- metabolism KW - Disease Models, Animal KW - Mice KW - Cell Death -- drug effects KW - Glutamic Acid -- pharmacology KW - Caspases -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Prodrugs -- pharmacology KW - Mitochondria -- drug effects KW - Mice, Inbred C57BL KW - Mitochondria -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Seizures -- chemically induced KW - Toluene -- analogs & derivatives KW - Neurons -- metabolism KW - Brain Ischemia -- prevention & control KW - Neurons -- drug effects KW - Seizures -- drug therapy KW - Tumor Suppressor Protein p53 -- metabolism KW - Thiazoles -- pharmacology KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Toluene -- pharmacology KW - Brain Ischemia -- drug therapy KW - Amyloid beta-Peptides -- pharmacology KW - Neurons -- cytology KW - Brain Ischemia -- metabolism KW - Seizures -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77012379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=A+synthetic+inhibitor+of+p53+protects+neurons+against+death+induced+by+ischemic+and+excitotoxic+insults%2C+and+amyloid+beta-peptide.&rft.au=Culmsee%2C+C%3BZhu%2C+X%3BYu%2C+Q+S%3BChan%2C+S+L%3BCamandola%2C+S%3BGuo%2C+Z%3BGreig%2C+N+H%3BMattson%2C+M+P&rft.aulast=Culmsee&rft.aufirst=C&rft.date=2001-04-01&rft.volume=77&rft.issue=1&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genetics of alcoholism and alcohol abuse. AN - 77011530; 11276410 AB - Twin studies have established that there are substantial genetic influences on alcoholism (0.5-0.6) in both men and women. Our knowledge of behaviors predisposing to alcoholism, including anxiety and impulsivity, is advancing rapidly through animal and human studies. Although alcoholism is often comorbid with other substance abuse and psychiatric disorders, recent studies have shown that, with the exception of nicotine, the heritability of alcoholism is largely substance-specific. Increasing understanding of the neurobiology of addiction has identified neural pathways in which genetic variation at candidate genes could influence vulnerability. Some functional variants of these genes have been identified. Recent linkage analyses in humans and rodents have pointed to genomic regions harboring genes that influence alcoholism. Refinement of clinical phenotypes and use of intermediate phenotypes will improve chances of gene identification. All these advances in the understanding of the genetics of alcoholism should facilitate the development of more accurately targeted therapies using molecular diagnostic approaches. JF - Current psychiatry reports AU - Enoch, M A AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Drive, Park 5 Building, Room 451, MSC 8110, Bethesda, MD 20892-8110, USA. maenoch@dicbr.niaaa.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 144 EP - 151 VL - 3 IS - 2 SN - 1523-3812, 1523-3812 KW - Central Nervous System Depressants KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Phenotype KW - Genetic Linkage KW - Mental Disorders -- genetics KW - Central Nervous System Depressants -- metabolism KW - Humans KW - Twin Studies as Topic KW - Ethanol -- metabolism KW - Disruptive, Impulse Control, and Conduct Disorders KW - Comorbidity KW - Genetic Predisposition to Disease KW - Alcoholism -- genetics KW - Behavior, Addictive -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77011530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+psychiatry+reports&rft.atitle=The+genetics+of+alcoholism+and+alcohol+abuse.&rft.au=Enoch%2C+M+A%3BGoldman%2C+D&rft.aulast=Enoch&rft.aufirst=M&rft.date=2001-04-01&rft.volume=3&rft.issue=2&rft.spage=144&rft.isbn=&rft.btitle=&rft.title=Current+psychiatry+reports&rft.issn=15233812&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-23 N1 - Date created - 2001-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity. AN - 77010724; 11276204 AB - Fas ligand (CD95L) is synthesized both on the cell surface membrane and in a soluble form. Although CD95L contributes to immune privilege in the cornea and testis, the functions of these alternatively processed proteins are not well understood. Some reports suggest that the cytotoxicity of soluble CD95L is insignificant, whereas others show potent responses in vivo, including hepatocyte apoptosis that causes liver failure. We show here that extracellular matrix proteins interact with soluble CD95L and potentiate its pro-apoptotic activity. The cytotoxicity of supernatants from CD95L-expressing cells was increased by incubation on tissue culture plates coated with these matrix proteins; this effect was mediated by trimeric soluble CD95L. With the use of immunoprecipitation, it was found that CD95L binds directly to fibronectin. In addition, immunohistochemical analysis of the cornea revealed that soluble CD95L binds primarily to extracellular matrix. The retention of soluble CD95L on extracellular matrices is likely to play an important role in the development of peripheral tolerance in immune-privileged sites. JF - Nature immunology AU - Aoki, K AU - Kurooka, M AU - Chen, J J AU - Petryniak, J AU - Nabel, E G AU - Nabel, G J AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892-3005, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 333 EP - 337 VL - 2 IS - 4 SN - 1529-2908, 1529-2908 KW - DNA Primers KW - 0 KW - FASLG protein, human KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Ligands KW - Membrane Glycoproteins KW - Index Medicus KW - Animals KW - Solubility KW - Apoptosis KW - DNA Primers -- genetics KW - Humans KW - Mice KW - Immune Tolerance KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Eye -- immunology KW - Signal Transduction KW - Cell Line KW - Male KW - Testis -- immunology KW - Membrane Glycoproteins -- chemistry KW - Cytotoxicity, Immunologic KW - Extracellular Matrix -- immunology KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77010724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+immunology&rft.atitle=Extracellular+matrix+interacts+with+soluble+CD95L%3A+retention+and+enhancement+of+cytotoxicity.&rft.au=Aoki%2C+K%3BKurooka%2C+M%3BChen%2C+J+J%3BPetryniak%2C+J%3BNabel%2C+E+G%3BNabel%2C+G+J&rft.aulast=Aoki&rft.aufirst=K&rft.date=2001-04-01&rft.volume=2&rft.issue=4&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Nature+immunology&rft.issn=15292908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. AN - 76994813; 11264389 AB - The potential roles of an amino acid deletion at codon 67 (Delta67) and a Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase of human immunodeficiency virus (HIV) type 1 in drug sensitivity and relative replication fitness were studied. Our results suggest that the Delta67 and T69G changes can be categorized as mutations associated with multidrug resistance. The combination of both mutations with an L74I change (Delta67+T69G/L74I) leads to a novel 3'-azido-3'-deoxythymidine resistance motif and compensates for impaired HIV replication. JF - Journal of virology AU - Imamichi, T AU - Murphy, M A AU - Imamichi, H AU - Lane, H C AD - Laboratory of Molecular Retrovirology, Clinical Services Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA. timamichi@nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 3988 EP - 3992 VL - 75 IS - 8 SN - 0022-538X, 0022-538X KW - Anti-HIV Agents KW - 0 KW - Codon KW - Reverse Transcriptase Inhibitors KW - Threonine KW - 2ZD004190S KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Threonine -- genetics KW - Threonine -- metabolism KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Glycine -- metabolism KW - Humans KW - Glycine -- genetics KW - Amino Acid Motifs KW - Tumor Cells, Cultured KW - Virus Replication -- drug effects KW - Anti-HIV Agents -- pharmacology KW - Genetic Variation -- genetics KW - Inhibitory Concentration 50 KW - Drug Resistance, Multiple -- genetics KW - HIV Reverse Transcriptase -- genetics KW - HIV-1 -- genetics KW - Codon -- genetics KW - Amino Acid Substitution -- genetics KW - Sequence Deletion -- genetics KW - Drug Resistance, Microbial -- genetics KW - HIV Reverse Transcriptase -- metabolism KW - HIV-1 -- enzymology KW - HIV Reverse Transcriptase -- chemistry KW - HIV-1 -- physiology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76994813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Amino+acid+deletion+at+codon+67+and+Thr-to-Gly+change+at+codon+69+of+human+immunodeficiency+virus+type+1+reverse+transcriptase+confer+novel+drug+resistance+profiles.&rft.au=Imamichi%2C+T%3BMurphy%2C+M+A%3BImamichi%2C+H%3BLane%2C+H+C&rft.aulast=Imamichi&rft.aufirst=T&rft.date=2001-04-01&rft.volume=75&rft.issue=8&rft.spage=3988&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Hum Virol. 1999 Sep-Oct;2(5):290-5 [10551735] Mol Cell. 1999 Jul;4(1):35-43 [10445025] J Virol. 2000 Jan;74(2):1023-8 [10623768] J Hum Virol. 2000 May-Jun;3(3):144-9 [10881994] J Virol. 2000 Sep;74(18):8390-401 [10954539] J Virol. 2000 Nov;74(22):10707-13 [11044115] J Virol. 2000 Dec;74(23):10958-64 [11069990] Science. 1985 Aug 9;229(4713):563-6 [2992081] J Virol. 1986 Aug;59(2):284-91 [3016298] J Biol Chem. 1988 Apr 25;263(12):5870-5 [3258602] Antimicrob Agents Chemother. 1992 Dec;36(12):2664-9 [1282792] Antimicrob Agents Chemother. 1994 Jun;38(6):1404-7 [7522428] J Mol Biol. 1994 Oct 28;243(3):369-87 [7525966] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):34-8 [8552634] J Virol. 1997 Sep;71(9):6662-70 [9261388] AIDS. 1998 Oct 1;12(14):F161-6 [9792372] J Clin Invest. 1998 Nov 15;102(10):1769-75 [9819361] Science. 1998 Nov 27;282(5394):1669-75 [9831551] AIDS. 1999 Jan 14;13(1):75-80 [10207547] Antimicrob Agents Chemother. 1999 Aug;43(8):1961-7 [10428920] J Clin Microbiol. 1999 Dec;37(12):4099-106 [10565938] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma. AN - 76994266; 11264156 AB - We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 microg/m(2) daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 microg/m(2) twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P =.0074). The mean duration of neutropenia was reduced by GM-CSF priming: grade 3 neutropenia from 5.2 +/- 0.7 to 2.8 +/- 0.7 days (P =.0232) and grade 4 neutropenia from 2.7 +/- 0.6 to 1.1 +/- 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy. (Blood. 2001;97:1942-1946) JF - Blood AU - Janik, J E AU - Miller, L L AU - Korn, E L AU - Stevens, D AU - Curti, B D AU - Smith, J W AU - Sznol, M AU - Conlon, K C AU - Sharfman, W AU - Urba, W J AU - Gause, B L AU - Longo, D L AD - Frederick Cancer Research and Development Center, Biological Response Modifiers Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. janikj@mail.nih.gov Y1 - 2001/04/01/ PY - 2001 DA - 2001 Apr 01 SP - 1942 EP - 1946 VL - 97 IS - 7 SN - 0006-4971, 0006-4971 KW - Antineoplastic Agents KW - 0 KW - Topotecan KW - 7M7YKX2N15 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Hypotension -- chemically induced KW - Prospective Studies KW - Diabetes Mellitus, Type 1 -- complications KW - Humans KW - Premedication KW - Anemia -- chemically induced KW - Treatment Outcome KW - Thrombocytopenia -- chemically induced KW - Stroke -- etiology KW - Remission Induction KW - Topotecan -- adverse effects KW - Kidney Neoplasms -- drug therapy KW - Melanoma -- blood KW - Neutropenia -- prevention & control KW - Neutropenia -- chemically induced KW - Carcinoma, Renal Cell -- drug therapy KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Topotecan -- therapeutic use KW - Skin Neoplasms -- blood KW - Antineoplastic Agents -- adverse effects KW - Skin Neoplasms -- drug therapy KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Kidney Neoplasms -- blood KW - Melanoma -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Carcinoma, Renal Cell -- blood KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76994266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=A+prospective+randomized+phase+II+trial+of+GM-CSF+priming+to+prevent+topotecan-induced+neutropenia+in+chemotherapy-naive+patients+with+malignant+melanoma+or+renal+cell+carcinoma.&rft.au=Janik%2C+J+E%3BMiller%2C+L+L%3BKorn%2C+E+L%3BStevens%2C+D%3BCurti%2C+B+D%3BSmith%2C+J+W%3BSznol%2C+M%3BConlon%2C+K+C%3BSharfman%2C+W%3BUrba%2C+W+J%3BGause%2C+B+L%3BLongo%2C+D+L&rft.aulast=Janik&rft.aufirst=J&rft.date=2001-04-01&rft.volume=97&rft.issue=7&rft.spage=1942&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. AN - 76988265; 11259636 AB - The antitumorigenic activity of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase (COX) inhibitors, is well established, but responsible molecular mechanisms are not fully understood. NSAIDs stimulate apoptosis by COX dependent and independent mechanisms in colorectal cells in culture. Identification of genes regulated by COX inhibitors could lead to a better understanding of their proapoptotic and anti-neoplastic activities. Using subtractive hybridization, a cDNA which was designated as NSAID activated gene (NAG-1) was identified from NSAID-treated HCT-116, human colorectal cells. NAG-1 has an identical sequence with a novel member of the TGF-beta superfamily that has 5 different names. In the HCT-116 cells, NAG-1 expression is increased and apoptosis is induced by treatment with some NSAIDs in a concentration and time-dependent manner. NAG-1 transfected cells exhibited increased basal apoptosis, increased response to NSAIDs and reduced soft agar cloning efficiency. Furthermore, transplantable tumors derived from NAG-1 transfected HCT-116 cells showed reduced tumorigenicity in athymic nude mice compared with vector-transfected HCT-116 cells. The increased NAG-1 expression by NSAIDs provides a suitable explanation for COX-independent apoptotic effects of NSAIDs in cultured cells. These data demonstrate that NAG-1 is an antitumorigenic and proapoptotic protein, and its regulation by COX inhibitors may provide new clues for explaining their proapoptotic and antitumorigenic activities. JF - Molecular pharmacology AU - Baek, S J AU - Kim, K S AU - Nixon, J B AU - Wilson, L C AU - Eling, T E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 901 EP - 908 VL - 59 IS - 4 SN - 0026-895X, 0026-895X KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Antineoplastic Agents KW - Cyclooxygenase Inhibitors KW - Cytokines KW - GDF15 protein, human KW - Gdf15 protein, mouse KW - Growth Differentiation Factor 15 KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Transfection KW - Molecular Sequence Data KW - Xenograft Model Antitumor Assays KW - Transforming Growth Factor beta -- genetics KW - Tumor Stem Cell Assay KW - Male KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Cytokines -- genetics KW - Cytokines -- pharmacology KW - Apoptosis KW - Colorectal Neoplasms -- metabolism KW - Cytokines -- biosynthesis KW - Antineoplastic Agents -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Cyclooxygenase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76988265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Cyclooxygenase+inhibitors+regulate+the+expression+of+a+TGF-beta+superfamily+member+that+has+proapoptotic+and+antitumorigenic+activities.&rft.au=Baek%2C+S+J%3BKim%2C+K+S%3BNixon%2C+J+B%3BWilson%2C+L+C%3BEling%2C+T+E&rft.aulast=Baek&rft.aufirst=S&rft.date=2001-04-01&rft.volume=59&rft.issue=4&rft.spage=901&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-03-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF173860; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostaglandin A(1) protects striatal neurons against excitotoxic injury in rat striatum. AN - 76987969; 11259530 AB - Prostaglandin A(1) (PGA1) reportedly inhibits NF-kappaB activation and induces expression of heat shock proteins. Since both these effects could be neuroprotective, the therapeutic potential of PGA1 in neurodegenerative disorders, where excitotoxicity may contribute to pathogenesis, was evaluated in rat striatal neurons exposed to the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid (QA). Intrastriatal administration of PGA1 (5-80 nmol) attenuated QA (60 nmol)-induced internucleosomal DNA fragmentation. The inhibitory effects of a single dose of PGA1 (80 nmol) on QA (60 nmol)-induced DNA fragmentation were observed 12 to 48 h after treatment. PGA1 (80 nmol) also attenuated QA-induced DNA fragmentation when administered up to 4 h after QA exposure. PGA1 significantly decreased the loss of D1 dopamine receptors and GAD(67) mRNA in QA-injected striatum as measured by quantitative receptor autoradiography and in situ hybridization histochemistry, suggesting that it reduced the neuronal loss induced by QA. Protection of striatal neurons against QA-induced death by PGA1 was further indicated by Nissl staining 10 days after QA administration. PGA1 (5-80 nmol) significantly inhibited QA-induced NF-kappaB activation by blocking inhibitory kappaB-alpha degradation but had no effect on activator protein-1 binding activity. PGA1 (80 nmol) treatment substantially increased 70- and 72-kDa heat shock protein levels in striatum. These results indicate that PGA1 blunts NMDA receptor-mediated neuronal apoptosis by a mechanism possibly involving the up-regulation of neuroprotective heat shock proteins and inhibition of NF-kappaB activation. In view of its potent neuroprotective activity, PGA1 could prove useful in the treatment of certain neurodegenerative disorders related to excitotoxicity. JF - The Journal of pharmacology and experimental therapeutics AU - Qin, Z H AU - Wang, Y AU - Chen, R W AU - Wang, X AU - Ren, M AU - Chuang, D M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurodegenerative Disorders and Stroke, National Institutes of Health, Bldg. 10, 10 Center Drive, Bethesda, MD 20892-1406, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 78 EP - 87 VL - 297 IS - 1 SN - 0022-3565, 0022-3565 KW - HSP70 Heat-Shock Proteins KW - 0 KW - NF-kappa B KW - Nucleosomes KW - Prostaglandins A KW - Quinolinic Acid KW - F6F0HK1URN KW - prostaglandin A1 KW - VYR271N44P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - HSP70 Heat-Shock Proteins -- biosynthesis KW - Nucleosomes -- drug effects KW - Apoptosis -- drug effects KW - DNA Fragmentation -- drug effects KW - Male KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - Prostaglandins A -- pharmacology KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects KW - Quinolinic Acid -- toxicity KW - Corpus Striatum -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76987969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Prostaglandin+A%281%29+protects+striatal+neurons+against+excitotoxic+injury+in+rat+striatum.&rft.au=Qin%2C+Z+H%3BWang%2C+Y%3BChen%2C+R+W%3BWang%2C+X%3BRen%2C+M%3BChuang%2C+D+M%3BChase%2C+T+N&rft.aulast=Qin&rft.aufirst=Z&rft.date=2001-04-01&rft.volume=297&rft.issue=1&rft.spage=78&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosome 11 loss from thymic lymphomas induced in heterozygous Trp53 mice by phenolphthalein. AN - 76974511; 11248138 AB - C57BL/6 p53 (+/-) N5 mice heterozygous for a null p53 allele were given phenolphthalein to learn more about mechanisms of carcinogenesis and to evaluate the p53-deficient mouse as a tool for identifying potential human carcinogens. DNA samples isolated from 10 phenolphthalein-induced thymic lymphomas were analyzed for loss of heterozygosity (LOH) at the Trp53 locus and simple sequence length polymorphic (SSLP) loci. The initial screening revealed remarkable results from only chromosome 11. Allelotyping at approximately five centiMorgan intervals, we found SSLP heterozygosity for C57BL/6 and 129Sv over much of chromosome 11. In the tumors, treatment-related LOH was apparent on chromosome 11 at each of the 28 informative loci examined. The strain-specific polymorphism lost from individual tumors allowed us to deduce the distribution of alleles along the length of the maternal and paternal chromosomes 11. The allelic patterns indicate that mitotic homologous recombination occurred during embryogenesis if breeding protocols were carried out as described. The mitotic recombination observed may be attributable to p53 haploinsufficiency for normal suppression of mitotic recombination. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Hulla, J E AU - French, J E AU - Dunnick, J K AD - University of North Dakota School of Medicine, Grand Forks, ND, USA. hulla@niehs.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 264 EP - 270 VL - 60 IS - 2 SN - 1096-6080, 1096-6080 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Phenolphthalein KW - 6QK969R2IF KW - Index Medicus KW - Animals KW - Polymorphism, Genetic KW - Heterozygote KW - Mice, Inbred C57BL KW - Mice KW - DNA, Neoplasm -- analysis KW - Mice, Knockout KW - DNA Primers -- chemistry KW - Loss of Heterozygosity KW - Lymphoma -- genetics KW - Thymus Neoplasms -- genetics KW - Thymus Neoplasms -- chemically induced KW - Lymphoma -- chemically induced KW - Phenolphthalein -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76974511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Chromosome+11+loss+from+thymic+lymphomas+induced+in+heterozygous+Trp53+mice+by+phenolphthalein.&rft.au=Hulla%2C+J+E%3BFrench%2C+J+E%3BDunnick%2C+J+K&rft.aulast=Hulla&rft.aufirst=J&rft.date=2001-04-01&rft.volume=60&rft.issue=2&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-03-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Toxicol Sci. 2001 Dec;64(2):281-2 [11719711] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resistance to growth inhibitory and apoptotic effects of phorbol ester and UCN-01 in aggressive cancer cell lines. AN - 76974132; 11251163 AB - 7-Hydroxystaurosporine (UCN-01), a non-selective inhibitor of protein kinase C (PKC), and phorbol ester (PMA), a PKC activator, are undergoing clinical evaluations. We investigated the effects of UCN-01 and PMA on a panel of prostate cancer cell lines. While PMA induced p21WAF1/CIP1 and arrest growth of LNCaP cancer cells (IC50 = 0.5-1 nM), aggressive cancer cell lines (DU145, PC3, and PC3M) were resistant to PMA (IC50 >5000 nM). Low concentrations (25-50 nM) of UCN-01 abrogated PMA-induced p21 and growth arrest in LNCaP cells. These low doses of UCN-01 however did not inhibit proliferation of any prostate cancer cell line. PMA-sensitive LNCaP cells were resistant to clinically relevant concentrations of UCN-01 (IC50 = 1.2 microM), but UCN-01 inhibited growth of DU145 and PC3/3M with an IC50 of 200-400 nM. For comparison, PMA-sensitive HL60 leukemia cells were sensitive to UCN-01 due to rapid apoptosis caused by UCN-01. In PMA-resistant prostate cancer cells, UCN-01 downregulated cyclin D1, induced p21, caused morphological differentiation, and G1-phase arrest leading to slow cell death without caspase activation. Importantly, normal prostate epithelial cells (PrEC) were very sensitive to both PMA (IC50 = 0.2 nM) and UCN-01. In PrEC, UCN-01 downregulated cyclin D1 and arrest growth with an IC50 less than 100 nM. We conclude that loss of sensitivity to either UCN-01 or PMA accompanies progression of prostate cancer. JF - International journal of oncology AU - Blagosklonny, M V AU - Dixon, S C AU - Robey, R AU - Figg, W D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bldg 10, 12N226, Bethesda, MD 20892, USA. mikhailb@box-m.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 697 EP - 704 VL - 18 IS - 4 SN - 1019-6439, 1019-6439 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA, Neoplasm KW - Formazans KW - Tetrazolium Salts KW - MTT formazan KW - 23305-68-2 KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Formazans -- metabolism KW - Immunoblotting KW - Tumor Cells, Cultured -- cytology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Cell Division -- drug effects KW - Drug Resistance, Neoplasm KW - Staurosporine -- analogs & derivatives KW - Tetrazolium Salts -- metabolism KW - Down-Regulation KW - Transfection KW - DNA, Neoplasm -- metabolism KW - Cell Cycle -- drug effects KW - Male KW - Signal Transduction KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- pathology KW - Apoptosis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cyclins -- metabolism KW - Alkaloids -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76974132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Resistance+to+growth+inhibitory+and+apoptotic+effects+of+phorbol+ester+and+UCN-01+in+aggressive+cancer+cell+lines.&rft.au=Blagosklonny%2C+M+V%3BDixon%2C+S+C%3BRobey%2C+R%3BFigg%2C+W+D&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2001-04-01&rft.volume=18&rft.issue=4&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis. AN - 76965270; 11245570 AB - The metanephric kidney develops from interactions between the epithelial ureteric bud and adjacent metanephric mesenchyme, which is induced by the bud to form the epithelia of the nephron. We have found that leukemia inhibitory factor (LIF) and transforming growth factor beta 2 (TGF beta 2) are secreted by inductive rat bud cells and cooperate to enhance and accelerate renal tubule formation in uninduced rat metanephric mesenchymal explants. LIF alone or TGF beta 2 with fibroblast growth factor 2 induced numerous tubules in isolated mesenchymes over an 8 day period, while (in combination) all three caused abundant tubule formation in 72 hours. Furthermore, neutralization of Wnt ligands with antagonist-secreted Frizzled-related protein 1 abrogated these responses and combinatorial cytokine/growth factor stimulation of explants augmented nuclear activation of Tcf1/Lef1, suggesting that LIF and TGF beta 2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-dependent mechanism. JF - Development (Cambridge, England) AU - Plisov, S Y AU - Yoshino, K AU - Dove, L F AU - Higinbotham, K G AU - Rubin, J S AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1045 EP - 1057 VL - 128 IS - 7 SN - 0950-1991, 0950-1991 KW - Biomarkers KW - 0 KW - Culture Media, Conditioned KW - Growth Inhibitors KW - Interleukin-6 KW - Leukemia Inhibitory Factor KW - Leukemia Inhibitory Factor Receptor alpha Subunit KW - Lifr protein, rat KW - Ligands KW - Lymphokines KW - Proto-Oncogene Proteins KW - Receptors, Cytokine KW - Receptors, OSM-LIF KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta2 KW - Wnt Proteins KW - Wnt4 Protein KW - Wnt4 protein, rat KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - transforming growth factor-beta type II receptor KW - Index Medicus KW - Animals KW - Receptors, Transforming Growth Factor beta -- genetics KW - Proto-Oncogene Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Rats KW - Receptors, Cytokine -- genetics KW - Time Factors KW - Fibroblast Growth Factor 2 -- metabolism KW - Lymphokines -- metabolism KW - Nephrons -- physiology KW - Growth Inhibitors -- genetics KW - Fibroblast Growth Factor 2 -- genetics KW - Lymphokines -- genetics KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Growth Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76965270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=TGF+beta+2%2C+LIF+and+FGF2+cooperate+to+induce+nephrogenesis.&rft.au=Plisov%2C+S+Y%3BYoshino%2C+K%3BDove%2C+L+F%3BHiginbotham%2C+K+G%3BRubin%2C+J+S%3BPerantoni%2C+A+O&rft.aulast=Plisov&rft.aufirst=S&rft.date=2001-04-01&rft.volume=128&rft.issue=7&rft.spage=1045&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development. AN - 76961270; 11245577 AB - All vertebrate eggs are surrounded by an extracellular matrix. This matrix is known as the zona pellucida in mammals and is critically important for the survival of growing oocytes, successful fertilization and the passage of early embryos through the oviduct. The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2 and ZP3), each encoded by a single copy gene. Using targeted mutagenesis in embryonic stem cells, Zp2-null mouse lines have been established. ZP1 and ZP3 proteins continue to be synthesized and form a thin zona matrix in early follicles that is not sustained in pre-ovulatory follicles. The abnormal zona matrix does not affect initial folliculogenesis, but there is a significant decrease in the number of antral stage follicles in ovaries isolated from mice lacking a zona pellucida. Few eggs are detected in the oviduct after stimulation with gonadotropins, and no two-cell embryos are recovered after mating Zp2-null females with normal male mice. The structural defect is more severe than that observed in Zp1-null mice, which have decreased fecundity, but not quite as severe as that observed in Zp3-null mice, which never form a visible zona pellucida and are sterile. Although zona-free oocytes matured and fertilized in vitro can progress to the blastocyst stage, the developmental potential of blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and, after transfer to foster mothers, live births have not been observed. Thus, in addition to its role in fertilization and protection of early embryos, these data are consistent with the zona pellucida maintaining interactions between granulosa cells and oocytes during folliculogenesis that are critical to maximize developmental competence of oocytes. JF - Development (Cambridge, England) AU - Rankin, T L AU - O'Brien, M AU - Lee, E AU - Wigglesworth, K AU - Eppig, J AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. tr44x@nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1119 EP - 1126 VL - 128 IS - 7 SN - 0950-1991, 0950-1991 KW - Egg Proteins KW - 0 KW - Membrane Glycoproteins KW - Receptors, Cell Surface KW - Zona Pellucida Glycoproteins KW - Zp1 protein, mouse KW - Zp2 protein, mouse KW - Zp3 protein, mouse KW - Index Medicus KW - Animals KW - Embryonic and Fetal Development KW - Ovary -- pathology KW - Mice, Inbred C57BL KW - Mice KW - Fertilization in Vitro KW - Gene Targeting KW - Male KW - Female KW - Mice, Knockout KW - Zona Pellucida -- physiology KW - Membrane Glycoproteins -- biosynthesis KW - Egg Proteins -- physiology KW - Ovarian Follicle -- physiology KW - Membrane Glycoproteins -- physiology KW - Egg Proteins -- genetics KW - Egg Proteins -- biosynthesis KW - Fertility -- physiology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76961270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Defective+zonae+pellucidae+in+Zp2-null+mice+disrupt+folliculogenesis%2C+fertility+and+development.&rft.au=Rankin%2C+T+L%3BO%27Brien%2C+M%3BLee%2C+E%3BWigglesworth%2C+K%3BEppig%2C+J%3BDean%2C+J&rft.aulast=Rankin&rft.aufirst=T&rft.date=2001-04-01&rft.volume=128&rft.issue=7&rft.spage=1119&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Changing Demographic Regime and Evolving Poly centric Urban Regions: Consequences for the Size, Composition and Distribution of City Populations AN - 759312064; 13501163 AB - The demographic regime in western Europe and many other countries of the developed world is now very different from that of 30-40 years ago and is continuing to evolve. At the same time, settlement systems have been altering significantly in spatial structure, notably in terms of the emergence of polycentric urban configurations. This paper examines the nature of these two sets of changes and searches for linkages between them. First, it outlines the main features of the changing demographic regime. Secondly, it attempts to identify what constitutes 'polycentric urban regions' as opposed to traditional monocentric structures. Thirdly, it assesses how recent demographic developments relate to traditional urban structures and discusses whether they are more conformable with polycentric urban forms. JF - Urban Studies AU - Champion, A G AD - Department of Geography, University of Newcastle, Newcastle upon Tyne, NEI 7RU, UK, Tony.Champion@newcastle.ac.uk Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 657 EP - 677 PB - Sage Publications, Inc., 2455 Teller Road Thousand Oaks CA 91320 USA VL - 38 IS - 4 SN - 0042-0980, 0042-0980 KW - Environment Abstracts; Sustainability Science Abstracts KW - demography KW - Europe KW - Urban areas KW - M3 1010:Issues in Sustainable Development KW - ENA 08:International UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/759312064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urban+Studies&rft.atitle=A+Changing+Demographic+Regime+and+Evolving+Poly+centric+Urban+Regions%3A+Consequences+for+the+Size%2C+Composition+and+Distribution+of+City+Populations&rft.au=Champion%2C+A+G&rft.aulast=Champion&rft.aufirst=A&rft.date=2001-04-01&rft.volume=38&rft.issue=4&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Urban+Studies&rft.issn=00420980&rft_id=info:doi/10.1080%2F00420980120035277 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - demography; Urban areas; Europe DO - http://dx.doi.org/10.1080/00420980120035277 ER - TY - JOUR T1 - Caloric restriction in primates and relevance to humans. AN - 72397712; 11795522 AB - Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies). To date, our results strongly suggest that the same beneficial "antiaging" and/or "antidisease" effects observed in CR rodents also occur in primates. These include lower plasma insulin levels and greater sensitivity; lower body temperatures; reduced cholesterol, triglycerides, blood pressure, and arterial stiffness; elevated HDL; and slower age-related decline in circulating levels of DHEAS. Collectively, these biomarkers suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age-related diseases and may in fact be aging more slowly than fully fed counterparts. Despite these very encouraging results, it is unlikely that most humans would be willing to maintain a 30% reduced diet for the bulk of their adult life span, even if it meant more healthy years. For this reason, we have begun to explore CR mimetics, agents that might elicit the same beneficial effects as CR, without the necessity of dieting. Our initial studies have focused on 2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that actually reduces glucose/energy flux without decreasing food intake in rats. In a six-month pilot study, 2DG lowered plasma insulin and body temperature in a manner analagous to that of CR. Thus, metabolic effects that mediate the CR mechanism can be attained pharmacologically. Doses were titrated to eliminate toxicity; a long-term longevity study is now under way. In addition, data from other laboratories suggest that at least some of the same physiological/metabolic end points that are associated with the beneficial effects of underfeeding may be obtained from other potential CR mimetic agents, some naturally occurring in food products. Much work remains to be done, but taken together, our successful results with CR in primates and 2DG administration to rats suggest that it may indeed be possible to obtain the health- and longevity-promoting effects of the former intervention without actually decreasing food intake. JF - Annals of the New York Academy of Sciences AU - Roth, G S AU - Ingram, D K AU - Lane, M A AD - Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. geor@vax.grc.nia.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 305 EP - 315 VL - 928 SN - 0077-8923, 0077-8923 KW - Biomarkers KW - 0 KW - Blood Glucose KW - Hypoglycemic Agents KW - Insulin KW - Lipids KW - Plant Preparations KW - Saponins KW - Triterpenes KW - gymnemoside A KW - gymnemoside B KW - gymnemic acid KW - 327O38FRK1 KW - Metformin KW - 9100L32L2N KW - Deoxyglucose KW - 9G2MP84A8W KW - Index Medicus KW - Lipids -- blood KW - Metformin -- pharmacology KW - Animals KW - Phytotherapy KW - Humans KW - Triterpenes -- therapeutic use KW - Garcinia KW - Blood Glucose -- analysis KW - Rats KW - Rats, Inbred F344 KW - Energy Metabolism -- drug effects KW - Saponins -- therapeutic use KW - Macaca mulatta KW - Neoplasms -- prevention & control KW - Medicine, Ayurvedic KW - Body Temperature -- drug effects KW - Diabetes Mellitus -- prevention & control KW - Insulin -- blood KW - Longevity -- drug effects KW - Cardiovascular Diseases -- prevention & control KW - Metformin -- therapeutic use KW - Saimiri KW - Hypoglycemic Agents -- therapeutic use KW - Plant Preparations -- therapeutic use KW - Insulin Resistance KW - Drug Evaluation, Preclinical KW - Aging -- metabolism KW - Primates -- physiology KW - Deoxyglucose -- therapeutic use KW - Aging -- drug effects KW - Diet, Reducing KW - Food Deprivation KW - Energy Intake KW - Deoxyglucose -- toxicity KW - Deoxyglucose -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72397712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Caloric+restriction+in+primates+and+relevance+to+humans.&rft.au=Roth%2C+G+S%3BIngram%2C+D+K%3BLane%2C+M+A&rft.aulast=Roth&rft.aufirst=G&rft.date=2001-04-01&rft.volume=928&rft.issue=&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein oxidation in aging and age-related diseases. AN - 72397534; 11795513 AB - Although different theories have been proposed to explain the aging process, it is generally agreed that there is a correlation between aging and the accumulation of oxidatively damaged proteins, lipids, and nucleic acids. Oxidatively modified proteins have been shown to increase as a function of age. Studies reveal an age-related increase in the level of protein carbonyl content, oxidized methionine, protein hydrophobicity, and cross-linked and glycated proteins as well as the accumulation of less active enzymes that are more susceptible to heat inactivation and proteolytic degredation. Factors that decelerate protein oxidation also increase the life span of animals and vice versa. Furthermore, a number of age-related diseases have been shown to be associated with elevated levels of oxidatively modified proteins. The chemistry of reactive oxygen species-mediated protein modification will be discussed. The accumulation of oxidatively modified proteins may reflect deficiencies in one or more parameters of a complex function that maintains a delicate balance between the presence of a multiplicity of prooxidants, antioxidants, and repair, replacement, or elimination of biologically damaged proteins. JF - Annals of the New York Academy of Sciences AU - Stadtman, E R AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0342, USA. erstadtman@nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 22 EP - 38 VL - 928 SN - 0077-8923, 0077-8923 KW - Amino Acids KW - 0 KW - Antioxidants KW - Cross-Linking Reagents KW - Oxidants KW - Peptides KW - Proteins KW - Reactive Oxygen Species KW - Peroxynitrous Acid KW - 14691-52-2 KW - Nitric Oxide KW - 31C4KY9ESH KW - 3-nitrotyrosine KW - 3604-79-3 KW - Tyrosine KW - 42HK56048U KW - Methionine KW - AE28F7PNPL KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Peroxynitrous Acid -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Apoptosis KW - Humans KW - Longevity -- physiology KW - Protein Denaturation KW - Nitric Oxide -- metabolism KW - Models, Biological KW - Rats KW - Oxidation-Reduction KW - Peroxynitrous Acid -- adverse effects KW - Antioxidants -- metabolism KW - Cysteine -- chemistry KW - Oxidants -- adverse effects KW - Peptides -- radiation effects KW - Antioxidants -- pharmacology KW - Peptides -- chemistry KW - Oxidants -- metabolism KW - Methionine -- chemistry KW - Cross-Linking Reagents -- adverse effects KW - Tyrosine -- adverse effects KW - Aging -- metabolism KW - Disease -- etiology KW - Proteins -- chemistry KW - Amino Acids -- chemistry KW - Oxidative Stress KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Proteins -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72397534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Protein+oxidation+in+aging+and+age-related+diseases.&rft.au=Stadtman%2C+E+R&rft.aulast=Stadtman&rft.aufirst=E&rft.date=2001-04-01&rft.volume=928&rft.issue=&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A study of the influence of the hydrophobic core residues of yeast iso-2-cytochrome c on phosphate binding: a probe of the hydrophobic core-surface charge interactions. AN - 71183086; 11565900 AB - To gain insight into the role of hydrophobic core-surface charge interactions in stabilizing cytochrome c, we investigated the influence of hydrophobic core residues on phosphate binding by mutating residues in yeast iso-2-cytochrome c to those corresponding to iso-l-cytochrome c in various combinations. Heat transition of ultraviolet CD was followed as a function of pH in the presence and absence of phosphate. Thermodynamic parameters were deduced. It was found that the I20V/V43A/M98L mutation in the hydrophobic core, whose locations are remote from the putative phosphate sites, modulates phosphate interactions. The modulation is pH dependent. The I20V/ M98L and V43A mutation effects are nonadditive. The results lead to a model analogous to that of Tsao, Evans, and Wennerstrom, where a domain associated with the ordered hydrophobic core is sensitive to the fields generated by the surface charges. Such an explanation would be in accord with the observed difference in thermal stability between iso-2 and horse cytochromes c. JF - Journal of protein chemistry AU - Taniuchi, H AU - Shi, Y AU - San Miguel, G I AU - Ferretti, J A AU - Mack, J W AU - Fisher, A AU - Shah, M AU - Schechter, A N AU - Shiloach, J AD - Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. htaniuch@helix.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 203 EP - 215 VL - 20 IS - 3 SN - 0277-8033, 0277-8033 KW - Cytochrome c Group KW - 0 KW - Fungal Proteins KW - Phosphates KW - iso-2-cytochrome C KW - Cytochromes c KW - 9007-43-6 KW - Index Medicus KW - Animals KW - Hydrophobic and Hydrophilic Interactions KW - Thermodynamics KW - Models, Molecular KW - Hydrogen-Ion Concentration KW - Temperature KW - Circular Dichroism KW - Amino Acid Sequence KW - Protein Binding KW - Mathematics KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Surface Properties KW - Phosphates -- metabolism KW - Fungal Proteins -- chemistry KW - Cytochrome c Group -- genetics KW - Fungal Proteins -- metabolism KW - Cytochrome c Group -- chemistry KW - Yeasts -- chemistry KW - Fungal Proteins -- genetics KW - Cytochrome c Group -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71183086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+protein+chemistry&rft.atitle=A+study+of+the+influence+of+the+hydrophobic+core+residues+of+yeast+iso-2-cytochrome+c+on+phosphate+binding%3A+a+probe+of+the+hydrophobic+core-surface+charge+interactions.&rft.au=Taniuchi%2C+H%3BShi%2C+Y%3BSan+Miguel%2C+G+I%3BFerretti%2C+J+A%3BMack%2C+J+W%3BFisher%2C+A%3BShah%2C+M%3BSchechter%2C+A+N%3BShiloach%2C+J&rft.aulast=Taniuchi&rft.aufirst=H&rft.date=2001-04-01&rft.volume=20&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Journal+of+protein+chemistry&rft.issn=02778033&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2001-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Protein Chem 2001 Aug;20(6):533 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ribose modified nucleosides and nucleotides as ligands for purine receptors. AN - 71179273; 11563046 AB - Molecular modeling of receptors for adenosine and nucleotide (P2) receptors with docked ligand, based on mutagenesis, was carried out. Adenosine 3',5'-bisphosphate derivatives act as selective P2Y1 antagonists/partial agonists. The ribose moiety was replaced with carbocyclics, smaller and larger rings, conformationally constrained rings, and acyclics, producing compounds that retained receptor affinity. Conformational constraints were built into the ribose rings of nucleoside and nucleotide ligands using the methanocarba approach, i.e. fused cyclopropane and cyclopentane rings in place of ribose, suggesting a preference for the Northern (N) conformation among ligands for P2Y1 and A1 and A3ARs. JF - Nucleosides, nucleotides & nucleic acids AU - Jacobson, K A AU - Ravi, R G AU - Nandanan, E AU - Kim, H S AU - Moro, S AU - Kim, Y C AU - Lee, K AU - Barak, D AU - Marquez, V E AU - Ji, X D AD - Molecular Recognition Section, LBC, NIDDK, National Inst. of Health, Bethesda, Maryland 20902, USA. PY - 2001 SP - 333 EP - 341 VL - 20 IS - 4-7 SN - 1525-7770, 1525-7770 KW - Ligands KW - 0 KW - Nucleosides KW - Nucleotides KW - P2RY1 protein, human KW - Purinergic P1 Receptor Agonists KW - Purinergic P1 Receptor Antagonists KW - Purinergic P2 Receptor Agonists KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P1 KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Ribose KW - 681HV46001 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Drug Design KW - Receptors, Purinergic P1 -- chemistry KW - Nucleotides -- metabolism KW - Ribose -- analogs & derivatives KW - Nucleosides -- metabolism KW - Receptors, Purinergic P2 -- metabolism KW - Nucleosides -- pharmacology KW - Receptors, Purinergic P2 -- chemistry KW - Receptors, Purinergic P1 -- metabolism KW - Nucleotides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71179273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleosides%2C+nucleotides+%26+nucleic+acids&rft.atitle=Ribose+modified+nucleosides+and+nucleotides+as+ligands+for+purine+receptors.&rft.au=Jacobson%2C+K+A%3BRavi%2C+R+G%3BNandanan%2C+E%3BKim%2C+H+S%3BMoro%2C+S%3BKim%2C+Y+C%3BLee%2C+K%3BBarak%2C+D%3BMarquez%2C+V+E%3BJi%2C+X+D&rft.aulast=Jacobson&rft.aufirst=K&rft.date=2001-04-01&rft.volume=20&rft.issue=4-7&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Nucleosides%2C+nucleotides+%26+nucleic+acids&rft.issn=15257770&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-09 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic breast cancer. AN - 71102525; 11510693 AB - Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical stages of lung development and carcinogenesis. To determine if the expression of hnRNP-A2/B1 is an informative biomarker in breast carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in archived specimens. Expression was detected in 48/85 (56.5%) primary invasive breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1 expression compared to normal or transformed breast cells. Expression of hnRNP-A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately with decreased cell growth. These results warrant further evaluation of hnRNP-A2/B1 as a marker of breast carcinogenesis. JF - Breast cancer research and treatment AU - Zhou, J AU - Allred, D C AU - Avis, I AU - Martínez, A AU - Vos, M D AU - Smith, L AU - Treston, A M AU - Mulshine, J L AD - Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 217 EP - 224 VL - 66 IS - 3 SN - 0167-6806, 0167-6806 KW - Biomarkers, Tumor KW - 0 KW - DNA-Binding Proteins KW - Heterogeneous-Nuclear Ribonucleoprotein Group A-B KW - Index Medicus KW - Neoplasm Invasiveness KW - Humans KW - Lung Neoplasms -- genetics KW - Immunohistochemistry KW - Female KW - Lung Neoplasms -- pathology KW - Cell Division KW - Gene Expression Regulation, Neoplastic KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- pathology KW - DNA-Binding Proteins -- biosynthesis KW - Biomarkers, Tumor -- analysis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71102525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Differential+expression+of+the+early+lung+cancer+detection+marker%2C+heterogeneous+nuclear+ribonucleoprotein-A2%2FB1+%28hnRNP-A2%2FB1%29+in+normal+breast+and+neoplastic+breast+cancer.&rft.au=Zhou%2C+J%3BAllred%2C+D+C%3BAvis%2C+I%3BMart%C3%ADnez%2C+A%3BVos%2C+M+D%3BSmith%2C+L%3BTreston%2C+A+M%3BMulshine%2C+J+L&rft.aulast=Zhou&rft.aufirst=J&rft.date=2001-04-01&rft.volume=66&rft.issue=3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-26 N1 - Date created - 2001-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A direct chemical interaction between dynorphin and excitatory amino acids. AN - 71098687; 11495350 AB - The endogenous opioid peptide dynorphin A elicits non-opioid receptor-mediated neurotoxic effects. These effects are blocked by pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists. Herein, the mechanism for the non-opioid effects of dynorphin and related peptides was studied by matrix-assisted laser desorption ionization (MALDI) mass-spectrometry. We observed that both glutamate or aspartate bind non-covalently to dynorphin A and dynorphin 2-17. However, when dynorphin A or dynorphin 2-17 were added to an equimolar mixture of Glutamate and Aspartate, they both complexed preferentially with glutamate. These data may explain the non-opioid physiological effects of dynorphin A and related peptides and indicate that the direct chemical interaction between neurotransmitters should be monitored when studying interactions between different neurochemical systems. JF - Neurochemical research AU - Woods, A AU - Zangen, A AD - National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA. awoods@intra.nida.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 395 EP - 400 VL - 26 IS - 4 SN - 0364-3190, 0364-3190 KW - Excitatory Amino Acids KW - 0 KW - Dynorphins KW - 74913-18-1 KW - Index Medicus KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Dynorphins -- chemistry KW - Excitatory Amino Acids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71098687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemical+research&rft.atitle=A+direct+chemical+interaction+between+dynorphin+and+excitatory+amino+acids.&rft.au=Woods%2C+A%3BZangen%2C+A&rft.aulast=Woods&rft.aufirst=A&rft.date=2001-04-01&rft.volume=26&rft.issue=4&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Neurochemical+research&rft.issn=03643190&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-02 N1 - Date created - 2001-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids. AN - 71053351; 11478385 AB - The concentration of the major polyunsaturated fatty acid (PUFA) in brain, docosahexaenoate, may be markedly reduced by two or more generations of dietary restriction of sources of n-3 fatty acids in the diet. Such a deficiency was induced through the feeding of safflower oil as the principal source of essential fatty acids. The reference point for this diet was an n-3 adequate diet to which alpha-linoleate and docosahexaenoate were added through the addition of a small quantity of flax seed or algael oils, respectively. The loss of brain DHA was associated with poorer performance in spatial tasks and an olfactory-cued reversal learning task. No difference could be observed in the hippocampal gross morphology. This study demonstrates the importance of providing a source of n-3 fatty acids during mammalian growth and development. JF - Journal of molecular neuroscience : MN AU - Salem, N AU - Moriguchi, T AU - Greiner, R S AU - McBride, K AU - Ahmad, A AU - Catalan, J N AU - Slotnick, B AD - Division of Intramural Clinical and Biological Research, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA. nsalem@niaaa.nih.gov PY - 2001 SP - 299 EP - 307; discussion 317-21 VL - 16 IS - 2-3 SN - 0895-8696, 0895-8696 KW - Dietary Fats KW - 0 KW - Fatty Acids, Omega-3 KW - Fatty Acids, Omega-6 KW - Fatty Acids, Unsaturated KW - Plant Oils KW - alpha-Linolenic Acid KW - 0RBV727H71 KW - Docosahexaenoic Acids KW - 25167-62-8 KW - Safflower Oil KW - 8001-23-8 KW - Linseed Oil KW - 8001-26-1 KW - coconut oil KW - Q9L0O73W7L KW - Index Medicus KW - Fatty Acids, Unsaturated -- pharmacokinetics KW - Animals KW - Maze Learning -- drug effects KW - Linseed Oil -- therapeutic use KW - Reversal Learning -- drug effects KW - alpha-Linolenic Acid -- pharmacology KW - alpha-Linolenic Acid -- administration & dosage KW - alpha-Linolenic Acid -- therapeutic use KW - Safflower Oil -- administration & dosage KW - Pregnancy KW - Hippocampus -- drug effects KW - Rats KW - Maternal-Fetal Exchange KW - Plant Oils -- administration & dosage KW - Smell -- drug effects KW - Smell -- physiology KW - Hippocampus -- pathology KW - Linseed Oil -- pharmacology KW - Female KW - Male KW - Prenatal Exposure Delayed Effects KW - Brain Chemistry -- drug effects KW - Fatty Acids, Omega-3 -- pharmacology KW - Fatty Acids, Omega-3 -- pharmacokinetics KW - Dietary Fats -- administration & dosage KW - Learning Disorders -- metabolism KW - Docosahexaenoic Acids -- therapeutic use KW - Learning Disorders -- prevention & control KW - Learning Disorders -- chemically induced KW - Brain -- physiopathology KW - Docosahexaenoic Acids -- pharmacokinetics KW - Fatty Acids, Omega-3 -- therapeutic use KW - Brain -- embryology KW - Dietary Fats -- therapeutic use KW - Fatty Acids, Omega-3 -- administration & dosage KW - Docosahexaenoic Acids -- administration & dosage KW - Dietary Fats -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71053351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+neuroscience+%3A+MN&rft.atitle=Alterations+in+brain+function+after+loss+of+docosahexaenoate+due+to+dietary+restriction+of+n-3+fatty+acids.&rft.au=Salem%2C+N%3BMoriguchi%2C+T%3BGreiner%2C+R+S%3BMcBride%2C+K%3BAhmad%2C+A%3BCatalan%2C+J+N%3BSlotnick%2C+B&rft.aulast=Salem&rft.aufirst=N&rft.date=2001-04-01&rft.volume=16&rft.issue=2-3&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=08958696&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-14 N1 - Date created - 2001-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lifetime prevalence of alcohol drinking, cigarette smoking, and solvent inhalation among junior high school students in Japan: tradition and urbanization. AN - 70917165; 11398340 AB - To estimate the lifetime prevalence of alcohol drinking, cigarette smoking, and solvent inhalation among general junior high school students in Chiba prefecture, the author surveyed 6,115 students enrolled in 14 junior high schools in 1992. The lifetime prevalence of alcohol drinking was 78.4% of male subjects, 72.8% of female subjects, and 75.6% of all subjects. The lifetime prevalence of cigarette smoking was 30.7%, 14.9%, and 22.9%, respectively. The lifetime prevalence of solvent inhalation was 2.5%, 1.2%, and 1.9%, respectively. The past-year prevalence of solvent inhalation was 1.8%, 0.9%, and 1.4%, respectively. Furthermore, to reveal the relationship between the prevalence of drug use and the regional characteristics, multiple regression analysis was performed, using 7 indices that seemed to represent the regional characteristics. The multiple regression analysis revealed the following: 1) that the lifetime prevalence of alcohol drinking and cigarette smoking had a strong standardized partial regression coefficient with the percentage of owner occupants (Mochiieritsu in Japanese) and 2) that the lifetime and the past-year prevalence of solvent inhalation had a strong standardized partial regression coefficient with the ratio of daytime population to nighttime population (Chuyakanjinkouhi in Japanese). The author considered that these coefficients represented the relationship between traditional lifestyle and urbanization and drug use among junior high school students in Japan. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Wada, K AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa-shi, Chiba-ken, 272-0827, Japan. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 124 EP - 141 VL - 36 IS - 2 SN - 1341-8963, 1341-8963 KW - Solvents KW - 0 KW - Index Medicus KW - Japan -- epidemiology KW - Humans KW - Adolescent KW - Male KW - Female KW - Culture KW - Urbanization KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70917165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=Lifetime+prevalence+of+alcohol+drinking%2C+cigarette+smoking%2C+and+solvent+inhalation+among+junior+high+school+students+in+Japan%3A+tradition+and+urbanization.&rft.au=Wada%2C+K&rft.aulast=Wada&rft.aufirst=K&rft.date=2001-04-01&rft.volume=36&rft.issue=2&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics of adrenocortical tumors: Carney complex. AN - 70875145; 11353891 AB - Adrenal cancer is a rare neoplasm; however, up to 1 in 1 500 adrenal incidentalomas may hide a carcinoma, which, if diagnosed late or left untreated, is associated with significant morbidity and mortality. Despite extensive investigation of the molecular mechanisms involved in adrenal carcinogenesis and significant improvements in diagnostic imaging, efforts to cure advanced adrenal cancer remain largely unsuccessful. Thus, the investigation of the genetics of adrenocortical cancer by the candidate or positional cloning gene approach is essential in the development of new therapies for this disease. We propose that adrenocortical tumorigenesis follows a pattern similar to that in other organs: As the pathology of the adrenocortical tumor increases towards malignancy, the genetic changes that are observed also increase. Known genetic associations, like TP53 gene changes, occur during the latest stages of adrenocortical tumorigenesis. Thus, it is essential to study the relatively few genes that are affected at the beginning of this process, at the stages of benign tumorigenesis in the cortex. We have studied primary pigmented adrenocortical disease (PPNAD), a benign, bilateral, adrenocortical hyperplasia, which either in its isolated form or as part of Carney complex (CNC), is inherited in an autosomal dominant manner and, therefore, the gene(s) responsible for this disorder could be identified by positional cloning approaches. Indeed, we have identified two genetic loci harboring genes for PPNAD and/or CNC on chromosomal loci 2p16 and 17q22-24. The chromosome 17 gene, PRKAR1A, was recently cloned and the identification of other responsible genes is currently under way in our, and collaborating laboratories. The present report reviews the genetics of adrenocortical cancer first, followed by what is known today about the genetics of PPNAD and/or CNC. JF - Annales d'endocrinologie AU - Stratakis, C A AD - Unit on Genetics and Endocrinology, DEB, NICHD, NIH, Building 10, Room 10N262, 10 Center Dr. MSC1862, Bethesda, Maryland 20892-1862, USA. stratakc@cc1.nichd.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 180 EP - 184 VL - 62 IS - 2 SN - 0003-4266, 0003-4266 KW - Index Medicus KW - Adrenal Cortex Diseases -- genetics KW - Molecular Biology KW - Syndrome KW - Humans KW - Heart Neoplasms -- genetics KW - Pigmentation Disorders -- genetics KW - Myxoma -- genetics KW - Multiple Endocrine Neoplasia -- genetics KW - Adrenal Cortex Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70875145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annales+d%27endocrinologie&rft.atitle=Genetics+of+adrenocortical+tumors%3A+Carney+complex.&rft.au=Stratakis%2C+C+A&rft.aulast=Stratakis&rft.aufirst=C&rft.date=2001-04-01&rft.volume=62&rft.issue=2&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=Annales+d%27endocrinologie&rft.issn=00034266&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integration of a c-myc transgene results in disruption of the mouse Gtf2ird1 gene, the homologue of the human GTF2IRD1 gene hemizygously deleted in Williams-Beuren syndrome. AN - 70852909; 11352562 AB - Transgenic mice expressing c-myc under the control of the albumin promoter and enhancer develop liver tumors and have served as a useful model for studying the progression of hepatocarcinogenesis. The chromosomes of one line of c-myc transgenic mice carry the reciprocal translocation t(5;6)(G1;F2) adjacent to the transgene insertion site on the 5G1-ter segment translocated to chromosome 6. To characterize the genomic alterations in the c-myc transgenic animals, we have cloned the mouse DNA flanking the transgene array. By linkage mapping, the transgene integration site was localized to the region of distal chromosome 5 syntenic to the region on human chromosome 7q11.23 that is hemizgygously deleted in Williams-Beuren syndrome, a multisystemic developmental disorder. Comparison of the genomic DNA structure in wildtype and transgenic mice revealed that the transgene integration had induced an approximately 40-kb deletion, starting downstream of the Cyln2 gene and including the first exon of the Gtf2ird1 gene. Gtf2ird1 encodes a polypeptide related to general transcription factor TFII-I, and it is the mouse orthologue of GTF2IRD1 (WBSCR11), one of the genes commonly deleted in Williams-Beuren syndrome patients. Loss of the 5' end of the Gtf2ird1 gene resulted in greatly reduced expression of Gtf2ird1 mRNA in mice homozygous for the transgene. JF - Genomics AU - Durkin, M E AU - Keck-Waggoner, C L AU - Popescu, N C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. marian_durkin@nih.gov Y1 - 2001/04/01/ PY - 2001 DA - 2001 Apr 01 SP - 20 EP - 27 VL - 73 IS - 1 SN - 0888-7543, 0888-7543 KW - RNA, Messenger KW - 0 KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Models, Animal KW - Genetic Linkage KW - Animals KW - Exons KW - Humans KW - Transgenes KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Chromosome Mapping -- methods KW - Chromosomes, Human, Pair 7 KW - Translocation, Genetic KW - Gene Deletion KW - Base Sequence KW - Helix-Loop-Helix Motifs KW - Molecular Sequence Data KW - Genes, myc KW - Williams Syndrome -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70852909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Integration+of+a+c-myc+transgene+results+in+disruption+of+the+mouse+Gtf2ird1+gene%2C+the+homologue+of+the+human+GTF2IRD1+gene+hemizygously+deleted+in+Williams-Beuren+syndrome.&rft.au=Durkin%2C+M+E%3BKeck-Waggoner%2C+C+L%3BPopescu%2C+N+C%3BThorgeirsson%2C+S+S&rft.aulast=Durkin&rft.aufirst=M&rft.date=2001-04-01&rft.volume=73&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-05-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF257475; GENBANK; AF257477; AF257476 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco use and oral disease. AN - 70838240; 11336115 AB - Tobacco use is a risk factor for oral cancer, oral mucosal lesions, periodontal disease and impaired healing after periodontal treatment, gingival recession, and coronal and root caries. Available evidence suggests that the risks of oral diseases increase with greater use of tobacco and that quitting smoking can result in decreased risk. The magnitude of the effect of tobacco on the occurrence of oral diseases is high, with users having many times the risk of non-users. There is a clear benefit to quitting tobacco use. The risks of oral cancer and periodontal disease decline as time from cessation increases, and some oral mucosal lesions may resolve with cessation of smokeless tobacco use. Smoking accounts for half of periodontal disease and three-fourths of oral cancers in the United States. Because tobacco accounts for such a high proportion of these diseases, comprehensive tobacco control policies are required to make progress in reducing the burden of tobacco-related oral diseases. Effective treatments to prevent tobacco use and increase cessation are available and need greater implementation. Dental practices may provide a uniquely effective setting for tobacco prevention and cessation. JF - Journal of dental education AU - Winn, D M AD - Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892-7395, USA. winnde@mail.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 306 EP - 312 VL - 65 IS - 4 SN - 0022-0337, 0022-0337 KW - Dentistry KW - Index Medicus KW - Dental Caries -- etiology KW - Leukoplakia, Oral -- etiology KW - Mouth Mucosa -- pathology KW - Humans KW - Mouth Neoplasms -- etiology KW - Tobacco, Smokeless -- adverse effects KW - Periodontal Diseases -- etiology KW - Stomatitis, Aphthous -- etiology KW - Male KW - Female KW - Plants, Toxic KW - Smoking -- adverse effects KW - Tobacco -- adverse effects KW - Mouth Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70838240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+dental+education&rft.atitle=Tobacco+use+and+oral+disease.&rft.au=Winn%2C+D+M&rft.aulast=Winn&rft.aufirst=D&rft.date=2001-04-01&rft.volume=65&rft.issue=4&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Journal+of+dental+education&rft.issn=00220337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of temperature and air pollutants on cardiovascular and respiratory diseases for males and females older than 65 years of age in Tokyo, July and August 1980-1995. AN - 70837432; 11335183 AB - We studied exposures to higher daily maximum temperatures and concentrations of air pollutants in Tokyo during the summer months of July and August from 1980 to 1995 and their effects on hospital emergency transports for cardiovascular and respiratory diseases for males and females > 65 years of age. Cardiovascular diseases were angina, cardiac insufficiency, hypertension, and myocardial infarction. Respiratory diseases were asthma, acute and chronic bronchitis, and pneumonia. Except for pneumonia, daily maximum temperatures were not associated with hospital emergency transports. Increasing daily maximum temperatures, however, were associated with decreased hospital emergency transports for hypertension. Concentrations of nitrogen dioxide or particulate matter < or = 10 microm, however, were associated with daily hospital emergency transports for angina, cardiac insufficiency, myocardial infarction, asthma, acute and chronic bronchitis, and pneumonia. For cardiac insufficiency, hypertension, myocardial infarction, asthma, chronic bronchitis, and pneumonia, the expected daily number of emergency transports per million were greater for males than for females. For angina and acute bronchitis, there were no differences for the expected daily numbers of emergency transports per million between males and females. JF - Environmental health perspectives AU - Ye, F AU - Piver, W T AU - Ando, M AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 355 EP - 359 VL - 109 IS - 4 SN - 0091-6765, 0091-6765 KW - Air Pollutants KW - 0 KW - Index Medicus KW - Japan -- epidemiology KW - Sex Factors KW - Epidemiologic Studies KW - Aged, 80 and over KW - Humans KW - Seasons KW - Temperature KW - Emergency Service, Hospital -- statistics & numerical data KW - Aged KW - Male KW - Female KW - Cardiovascular Diseases -- etiology KW - Cardiovascular Diseases -- epidemiology KW - Respiratory Tract Diseases -- etiology KW - Respiratory Tract Diseases -- epidemiology KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70837432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Effects+of+temperature+and+air+pollutants+on+cardiovascular+and+respiratory+diseases+for+males+and+females+older+than+65+years+of+age+in+Tokyo%2C+July+and+August+1980-1995.&rft.au=Ye%2C+F%3BPiver%2C+W+T%3BAndo%2C+M%3BPortier%2C+C+J&rft.aulast=Ye&rft.aufirst=F&rft.date=2001-04-01&rft.volume=109&rft.issue=4&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-23 N1 - Date created - 2001-05-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Rev Allergy Immunol. 1997 Summer;15(2):205-17 [9315412] Environ Res. 1997 Jan;72(1):24-31 [9012369] Am J Epidemiol. 1997 Nov 1;146(9):750-62 [9366623] Epidemiology. 1998 Mar;9(2):220-1 [9504300] Rev Environ Health. 1998 Jan-Jun;13(1-2):73-90 [9718623] J Toxicol Environ Health A. 1998 Oct 9;55(3):185-96 [9772102] Epidemiology. 1999 Jan;10(1):17-22 [9888275] Occup Environ Med. 1998 Oct;55(10):697-704 [9930092] Environ Health Perspect. 1999 Nov;107(11):911-6 [10544159] Environ Res. 1987 Aug;43(2):317-31 [3608935] Environ Res. 1988 Apr;45(2):224-41 [3349975] Environ Res. 1990 Feb;51(1):51-70 [2298182] Environ Res. 1991 Apr;54(2):99-120 [2029880] J Toxicol Clin Toxicol. 1991;29(3):385-400 [1920572] J Toxicol Clin Toxicol. 1991;29(3):401-11 [1920573] Am Rev Respir Dis. 1992 Mar;145(3):600-4 [1546841] Environ Res. 1992 Aug;58(2):184-94 [1511672] J Expo Anal Environ Epidemiol. 1993 Apr-Jun;3(2):181-202 [8241781] Am J Epidemiol. 1994 Mar 15;139(6):589-98 [8172170] Environ Res. 1994 May;65(2):172-94 [8187735] Environ Res. 1994 May;65(2):207-17 [8187737] Environ Health Perspect. 1994 Feb;102(2):186-9 [8033849] Biometrics. 1994 Mar;50(1):270-8 [8086610] Am J Respir Crit Care Med. 1994 Sep;150(3):648-55 [8087333] Arch Environ Health. 1994 Sep-Oct;49(5):366-74 [7944569] Am J Epidemiol. 1995 Jul 1;142(1):23-35 [7785670] Thorax. 1995 May;50(5):531-8 [7597667] Environ Health Perspect. 1995 Mar;103 Suppl 2:97-102 [7614954] Am J Public Health. 1995 Oct;85(10):1361-5 [7573618] Thorax. 1995 Oct;50(10):1051-6 [7491552] Am J Respir Crit Care Med. 1996 Jan;153(1):3-50 [8542133] Occup Environ Med. 1997 Feb;54(2):108-16 [9072018] Environ Health Perspect. 1997 Feb;105(2):216-22 [9105797] Lancet. 1997 May 31;349(9065):1582-7 [9174559] Epidemiology. 1997 Jul;8(4):371-7 [9209849] Epidemiology. 1997 Mar;8(2):162-7 [9229208] Environ Health Perspect. 1997 Jun;105(6):614-20 [9288496] Epidemiology. 1996 Jan;7(1):20-8 [8664396] J Expo Anal Environ Epidemiol. 1996 Jan-Mar;6(1):97-114 [8777376] Am J Respir Crit Care Med. 1997 Jan;155(1):122-9 [9001300] Occup Environ Med. 1997 Aug;54(8):535-40 [9326156] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco prevention and control in dental practice: the future. AN - 70822059; 11336124 AB - Tobacco use adversely affects oral health and dental care. Globally, the health consequences of tobacco use are worsening, particularly those caused by cigarette smoking. Concerned government and nongovernmental organizations are attempting to contain the transnational tobacco companies' promotion of tobacco use and its disregard for the serious health consequences. Dependence prevents most tobacco users from easily breaking free from their high-risk behavior. Evidence-based clinical treatment methods that substantially increase quit rates are available in the Public Health Service clinical practice guideline, Treating Tobacco Use and Dependence. Guideline recommendations are as useful to dental clinicians as to other health care disciplines. Dental educators have a strategic role in ensuring that clinicians are well informed and are skilled in and committed to providing tobacco prevention and cessation services to their patients. Dental organizations must identify and overcome perceived and real clinician and practice barriers to adopting essential cessation services. The dental profession is in an excellent position to play a major role in several emerging issues, such as helping the public and policymakers understand the chronic nature of tobacco dependence and supporting cessation services for all people, particularly pregnant women and youths. Such messages should be presented in terms that resonate with the public because tobacco industry activities and products continue to undermine well-being, the health economy, and individual self-directed behavior of choice. JF - Journal of dental education AU - Mecklenburg, R E AD - Tobacco Control Research Branch, National Cancer Institute, Potomac, MD 20854, USA. mecklenburg@Lan2Wan.com Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 375 EP - 384 VL - 65 IS - 4 SN - 0022-0337, 0022-0337 KW - Dentistry KW - Index Medicus KW - Education, Dental KW - Evidence-Based Medicine KW - Humans KW - Health Policy KW - Mouth Diseases -- etiology KW - Pregnancy KW - Plants, Toxic KW - Practice Guidelines as Topic KW - Program Development KW - Health Behavior KW - Tobacco Industry KW - Tobacco -- adverse effects KW - Female KW - Male KW - Dentists KW - Tobacco Use Cessation -- methods KW - Smoking -- adverse effects KW - Tobacco Use Disorder -- prevention & control KW - Smoking -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70822059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+dental+education&rft.atitle=Tobacco+prevention+and+control+in+dental+practice%3A+the+future.&rft.au=Mecklenburg%2C+R+E&rft.aulast=Mecklenburg&rft.aufirst=R&rft.date=2001-04-01&rft.volume=65&rft.issue=4&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Journal+of+dental+education&rft.issn=00220337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure of alkaloid 275A, a novel 1-azabicyclo[5.3.0]decane from a dendrobatid frog, Dendrobates lehmanni: synthesis of the tetrahydrodiastereomers. AN - 70815199; 11325220 AB - The principal alkaloid 275A in skins of the Colombian poison frog Dendrobates lehmanni has been identified as the pyrrolo[1,2-a]azepane (1), the first occurrence in nature of this "izidine" system. Tetrahydro-1 proved identical to one of the four synthetic diastereomers, 2a--2d, thereby establishing that 1 has the 5Z,10E relative stereochemistry. Alkaloid 1 is often accompanied by other congeners, in particular a 5Z,10Z diastereomer 15, a dihydro analogue 16, and a ketone 17. Such izidines in frogs may arise from dietary ants, as do other classes of izidines. JF - Journal of natural products AU - Garraffo, H M AU - Jain, P AU - Spande, T F AU - Daly, J W AU - Jones, T H AU - Smith, L J AU - Zottig, V E AD - Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, Maryland 20892-0820, USA. garraffo@helix.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 421 EP - 427 VL - 64 IS - 4 SN - 0163-3864, 0163-3864 KW - 1-azabicyclo(5.3.0)decane KW - 0 KW - Alkaloids KW - Aza Compounds KW - Bridged Bicyclo Compounds KW - Index Medicus KW - Molecular Structure KW - Animals KW - Stereoisomerism KW - Spectrum Analysis KW - Chromatography, Gas KW - Anura KW - Bridged Bicyclo Compounds -- chemical synthesis KW - Aza Compounds -- chemical synthesis KW - Alkaloids -- chemistry KW - Bridged Bicyclo Compounds -- chemistry KW - Aza Compounds -- chemistry KW - Alkaloids -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70815199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=Structure+of+alkaloid+275A%2C+a+novel+1-azabicyclo%5B5.3.0%5Ddecane+from+a+dendrobatid+frog%2C+Dendrobates+lehmanni%3A+synthesis+of+the+tetrahydrodiastereomers.&rft.au=Garraffo%2C+H+M%3BJain%2C+P%3BSpande%2C+T+F%3BDaly%2C+J+W%3BJones%2C+T+H%3BSmith%2C+L+J%3BZottig%2C+V+E&rft.aulast=Garraffo&rft.aufirst=H&rft.date=2001-04-01&rft.volume=64&rft.issue=4&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cannabinoid receptor activation and elevated cyclic AMP reduce glutamate neurotoxicity. AN - 70812961; 11328347 AB - Cannabinoid receptor activation in vivo reduces ischemic injury, a phenomenon that has not been successfully reproduced in vitro. Because cyclic adenosine monophosphate (cAMP) levels are radically elevated during ischemic reperfusion, but cannabinoid receptor activation reduces cAMP levels, we hypothesized that cannabinoids might prevent in vitro glutamate toxicity if reperfusion was simulated by cAMP supplementation after glutamate removal. Although neuronal cultures were unaffected by the single addition of either cannabinoid or dibutyryl cAMP (dbcAMP), glutamate toxicity was reduced by 20% when cannabinoid was present during glutamate exposure and either dbcAMP or forskolin was added after glutamate removal. Further studies revealed that cannabinoid receptor activation reduces glutamate toxicity by attenuating calcium influx through N- and P/Q-type calcium channels. The effect of glutamate exposure on neuronal cAMP levels was also examined. Glutamate exposure significantly reduced neuronal cAMP levels, although suppression was even greater when cannabinoid was present. Because neurological outcome after ischemia is poor when cAMP levels during reperfusion are low, it is hypothesized that cAMP elevation after glutamate exposure may offset excitotoxic and/or cannabinoid receptor-induced cAMP depletion. Cannabinoids protect against ischemic injury in vivo, but only reduce toxicity in vitro when cAMP levels are elevated, possibly suggesting that cAMP elevation during reperfusion reduces brain injury by off-setting the effect of Gi/o protein-coupled systems on adenylate cyclase. JF - The European journal of neuroscience AU - Hampson, A J AU - Grimaldi, M AD - Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, MD 20892, USA. aidan@codon.nih.gov Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 1529 EP - 1536 VL - 13 IS - 8 SN - 0953-816X, 0953-816X KW - Calcium Channels KW - 0 KW - Cannabinoids KW - Cyclohexanols KW - Neurotoxins KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Colforsin KW - 1F7A44V6OU KW - Glutamic Acid KW - 3KX376GY7L KW - Bucladesine KW - 63X7MBT2LQ KW - 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol KW - 83003-12-7 KW - Cyclic AMP KW - E0399OZS9N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Colforsin -- pharmacology KW - Calcium Channels -- metabolism KW - Rats, Wistar KW - Cyclohexanols -- pharmacology KW - Bucladesine -- pharmacology KW - Cannabinoids -- pharmacology KW - Cyclic AMP -- metabolism KW - Neurotoxins -- pharmacology KW - Glutamic Acid -- poisoning KW - Glutamic Acid -- drug effects KW - Receptors, Drug -- physiology KW - Neurotoxins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70812961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+European+journal+of+neuroscience&rft.atitle=Cannabinoid+receptor+activation+and+elevated+cyclic+AMP+reduce+glutamate+neurotoxicity.&rft.au=Hampson%2C+A+J%3BGrimaldi%2C+M&rft.aulast=Hampson&rft.aufirst=A&rft.date=2001-04-01&rft.volume=13&rft.issue=8&rft.spage=1529&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular dating and biogeography of the early placental mammal radiation AN - 52148690; 2002-014173 JF - The Journal of Heredity AU - Eizirik, E AU - Murphy, W J AU - O'Brien, S J Y1 - 2001/04// PY - 2001 DA - April 2001 SP - 212 EP - 219 PB - American Generic Association, Baltimore, MD VL - 92 IS - 2 SN - 0022-1503, 0022-1503 KW - lower Paleocene KW - Cretaceous KW - biogeography KW - Upper Cretaceous KW - Cenozoic KW - Theria KW - Paleocene KW - Gondwana KW - taxonomy KW - Eutheria KW - Chordata KW - phylogeny KW - Mammalia KW - biologic evolution KW - Paleogene KW - faunal list KW - Mesozoic KW - morphology KW - Tertiary KW - South America KW - K-T boundary KW - classification KW - DNA KW - Africa KW - stratigraphic boundary KW - Vertebrata KW - adaptive radiation KW - Tetrapoda KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52148690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Heredity&rft.atitle=Molecular+dating+and+biogeography+of+the+early+placental+mammal+radiation&rft.au=Eizirik%2C+E%3BMurphy%2C+W+J%3BO%27Brien%2C+S+J&rft.aulast=Eizirik&rft.aufirst=E&rft.date=2001-04-01&rft.volume=92&rft.issue=2&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Heredity&rft.issn=00221503&rft_id=info:doi/ L2 - http://jhered.oxfordjournals.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2002-01-01 N1 - Number of references - 39 N1 - PubXState - MD N1 - Document feature - illus. incl. 5 tables N1 - Last updated - 2012-06-07 N1 - CODEN - JOHEA8 N1 - SubjectsTermNotLitGenreText - adaptive radiation; Africa; biogeography; biologic evolution; Cenozoic; Chordata; classification; Cretaceous; DNA; Eutheria; faunal list; Gondwana; K-T boundary; lower Paleocene; Mammalia; Mesozoic; morphology; Paleocene; Paleogene; phylogeny; South America; stratigraphic boundary; taxonomy; Tertiary; Tetrapoda; Theria; Upper Cretaceous; Vertebrata ER - TY - JOUR T1 - Caspase-Mediated Suppression of Glutamate (AMPA) Receptor Channel Activity in Hippocampal Neurons in Response to DNA Damage Promotes Apoptosis and Prevents Necrosis: Implications for Neurological Side Effects of Cancer Therapy and Neurodegenerative Disorders AN - 20843920; 8068074 AB - DNA damage in neurons is implicated in the pathogenesis of several neurodegenerative disorders and may also contribute to the often severe neurological complications in cancer patients treated with chemotherapeutic agents. DNA damage can trigger apoptosis, a form of controlled cell death that involves activation of cysteine proteases called caspases. The excitatory neurotransmitter glutamate plays central roles in the activation of neurons and in processes such as learning and memory, but overactivation of ionotropic glutamate receptors can induce either apoptosis or necrosis. Glutamate receptors of the AM ( alpha -amino-3-hydroxy-5- JF - Neurobiology of Disease AU - Lu, Chengbiao AU - Fu, Weiming AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland, 21224 Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 194 EP - 206 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 8 IS - 2 SN - 0969-9961, 0969-9961 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; CSA Neurosciences Abstracts KW - Learning KW - Apoptosis KW - Channel gating KW - Hippocampus KW - Chemotherapy KW - Neurological complications KW - Glutamic acid receptors KW - alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors KW - Cancer KW - Glutamic acid receptors (ionotropic) KW - Neurodegenerative diseases KW - DNA damage KW - Memory KW - Necrosis KW - Nervous system KW - Neurons KW - Caspase KW - Neurotransmitters KW - Side effects KW - Cysteine proteinase KW - X 24310:Pharmaceuticals KW - N 14820:DNA Metabolism & Structure KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20843920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+Disease&rft.atitle=Caspase-Mediated+Suppression+of+Glutamate+%28AMPA%29+Receptor+Channel+Activity+in+Hippocampal+Neurons+in+Response+to+DNA+Damage+Promotes+Apoptosis+and+Prevents+Necrosis%3A+Implications+for+Neurological+Side+Effects+of+Cancer+Therapy+and+Neurodegenerative+Disorders&rft.au=Lu%2C+Chengbiao%3BFu%2C+Weiming%3BMattson%2C+Mark+P&rft.aulast=Lu&rft.aufirst=Chengbiao&rft.date=2001-04-01&rft.volume=8&rft.issue=2&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+Disease&rft.issn=09699961&rft_id=info:doi/10.1006%2Fnbdi.2000.0377 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Learning; Apoptosis; Channel gating; Hippocampus; Chemotherapy; Neurological complications; alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Cancer; DNA damage; Neurodegenerative diseases; Nervous system; Necrosis; Memory; Neurons; Caspase; Neurotransmitters; Side effects; Cysteine proteinase DO - http://dx.doi.org/10.1006/nbdi.2000.0377 ER - TY - JOUR T1 - Protocol: In vivo microdialysis in the visual cortex of awake cat : II: Sample analysis by microbore HPLC-electrochemical detection and capillary electrophoresis-laser-induced fluorescence detection AN - 20483368; 9181115 AB - Sampling and monitoring release of excitatory and inhibitory amino acids in the striate cortex of mammals will provide important information for visual system research. Two microbore high performance liquid chromatography-electrochemical detection methods and a capillary electrophoresis-laser induced fluorescence detection were developed to determine the inhibitory amino acid, gamma -aminobutyric acid and the excitatory amino acids, glutamate and aspartate in microdialysates of cat striate cortex. In the liquid chromatography method, samples were derivatized using OPA-TBT. Ten microliters of derivatized product was injected onto the microbore column (100X1 mm i.d., C8) for quantitative analysis. Electrochemical detection was employed. In the capillary electrophoresis method, samples were derivatized using fluorescein isothiocyanate and separated in borate buffer within 15 min, then detected by a laser-induced fluorescence detector. JF - Brain Research Protocols AU - Qu, Ying AU - Li, Yong-Min AU - Vandenbussche, Erik AU - Vandesande, Frans AU - Arckens, Lutgarde AD - Laboratory of Neuroendocrinology and Immunological Biotechnology, Zoological Institute, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium, quying@mail.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 45 EP - 51 PB - Elsevier BV VL - 7 IS - 1 SN - 1385-299X, 1385-299X KW - Microbiology Abstracts A: Industrial & Applied Microbiology; CSA Neurosciences Abstracts KW - In vivo microdialysis KW - HPLC KW - Electrochemical detection KW - Capillary electrophoresis KW - Laser-induced fluorescence KW - Amino acid KW - Fluorescein isothiocyanate KW - excitatory amino acids KW - Amino acids KW - Fluorescence KW - gamma -Aminobutyric acid KW - Visual system KW - Microdialysis KW - Liquid chromatography KW - Cortex (visual) KW - capillary electrophoresis KW - Glutamic acid KW - Sampling KW - Information systems KW - A 01310:Products of Microorganisms KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20483368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research+Protocols&rft.atitle=Protocol%3A+In+vivo+microdialysis+in+the+visual+cortex+of+awake+cat+%3A+II%3A+Sample+analysis+by+microbore+HPLC-electrochemical+detection+and+capillary+electrophoresis-laser-induced+fluorescence+detection&rft.au=Qu%2C+Ying%3BLi%2C+Yong-Min%3BVandenbussche%2C+Erik%3BVandesande%2C+Frans%3BArckens%2C+Lutgarde&rft.aulast=Qu&rft.aufirst=Ying&rft.date=2001-04-01&rft.volume=7&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Brain+Research+Protocols&rft.issn=1385299X&rft_id=info:doi/10.1016%2FS1385-299X%2800%2900061-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-04-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Fluorescein isothiocyanate; excitatory amino acids; Fluorescence; Amino acids; gamma -Aminobutyric acid; Visual system; Microdialysis; Cortex (visual); Liquid chromatography; capillary electrophoresis; Sampling; Glutamic acid; Information systems DO - http://dx.doi.org/10.1016/S1385-299X(00)00061-1 ER - TY - JOUR T1 - Pharmacogenetics of Alcohol Response and Alcoholism: The Interplay of Genes and Environmental Factors in Thresholds for Alcoholism AN - 18404399; 5389745 AB - Recent advances in neuroscience and genetics have enabled a better understanding of genetically influenced differences in ethanol ("alcohol")-related responses and differential vulnerability to alcohol dependence at the cellular and molecular levels. Heritability studies reveal that the role of genetic factors in alcoholism is largely substance-specific, with the exception of nicotine. One focus of genetic research in alcoholism is the study of functional polymorphisms influencing alcohol metabolism, such as the aldehyde dehydrogenase type 2 Glu487Lys and alcohol dehydrogenase type 2 His47Arg polymorphisms, which affect vulnerability to alcoholism via pharmacokinetic mechanisms, and cross-population studies have begun to reveal important gene-environment interactions. The other focus is on functional genetic variants of proteins involved in the neuronal response to alcohol, including alcohol sensitivity, reward, tolerance, and withdrawal. Studies on the roles of GABA sub(A) alpha 6-amino acid substitutions in rodents in alcohol and benzodiazepine sensitivity, and potential roles in human alcohol and benzodiazepine sensitivity are reviewed. These studies, together with recently developed knowledge on a GABA sub(A) receptor gene cluster at a quantitative trait loci for alcohol withdrawal on mouse chromosome 11, indicate that research investigation of variation at GABA sub(A) neurotransmission is a promising area in the pharmacodynamics of alcohol and in differential susceptibility to alcoholism. Genes for proteins involved in alcohol-mediated reward include genes for transporters and receptors for dopamine, serotonin, opioids, and GABA. These genes and their functional variants also represent important targets for understanding alcohol's effects in humans. Identification of genes for alcoholism vulnerability is important in the near future, not only for prevention, but also for development and targeting treatments. JF - Drug Metabolism and Disposition AU - Radel, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 489 EP - 494 VL - 29 IS - 4 SN - 0090-9556, 0090-9556 KW - man KW - pharmacogenetics KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18404399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+Metabolism+and+Disposition&rft.atitle=Pharmacogenetics+of+Alcohol+Response+and+Alcoholism%3A+The+Interplay+of+Genes+and+Environmental+Factors+in+Thresholds+for+Alcoholism&rft.au=Radel%2C+M%3BGoldman%2C+D&rft.aulast=Radel&rft.aufirst=M&rft.date=2001-04-01&rft.volume=29&rft.issue=4&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+and+Disposition&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Searching for Evidence About Health Education and Health Behavior Interventions AN - 18151153; 5109163 AB - Evidence is fundamental to science, but finding the right evidence in health education and health behavior (HEHB) is often a challenge. The authors discuss some of the controversies about the types of evidence that should be considered acceptable in HEHB, the tension between the use of qualitative versus quantitative data, the need for measures of important but neglected constructs, and interpretation of data from experimental and nonexperimental research. This article discusses some of the challenges to the use of evidence and describes a number of strategies and some forces encouraging the use of evidence-based interventions. Finally, the authors suggest ways to improve the practice and dissemination of evidence-based HEHB. Ultimately, if evidence-based interventions are not disseminated, the interventions will not achieve their potential. The goal should be to develop more effective interventions and disseminate them to improve the public's health. JF - Health Education & Behavior AU - Rimer, B K AU - Glanz, K AU - Rasband, G AD - National Cancer Institute, Bethesda, MD, USA, brimer@nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 231 EP - 248 VL - 28 IS - 2 SN - 1090-1981, 1090-1981 KW - Physical Education Index KW - Behavior KW - Health (education) KW - Public health KW - PE 010:Physical Education: Curriculum & Teaching Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18151153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Education+%26+Behavior&rft.atitle=Searching+for+Evidence+About+Health+Education+and+Health+Behavior+Interventions&rft.au=Rimer%2C+B+K%3BGlanz%2C+K%3BRasband%2C+G&rft.aulast=Rimer&rft.aufirst=B&rft.date=2001-04-01&rft.volume=28&rft.issue=2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Health+Education+%26+Behavior&rft.issn=10901981&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Health (education); Behavior; Public health ER - TY - JOUR T1 - Pharmacology of Phosphoinositides, Regulators of Multiple Cellular Functions AN - 18070409; 5111907 AB - Inositol phospholipids represent a small fraction of the phospholipids present in all cellular membranes with remarkable importance in regulating various cell functions. They are synthesized from phosphatidylinositol by sequential phosphorylations on the several hydroxyls of the inositol ring to create polyphosphoinositides that function either as docking sites to promote formation of molecular signaling complexes, or serve as precursors for soluble inositol polyphosphates that act as diffusible intracellular messengers. Phosphoinositides are involved in the control of many processes, including membrane traffic, endo- and exocytosis, mitogenesis and apoptosis. Pharmacological tools have helped to clarify many details of phosphoinositide metabolism and have unveiled the roles of these lipids in the control of specific signaling pathways. However, because of their pleiotropic functions it has been questionable whether pharmacological manipulation of inositide formation and metabolism can be of therapeutic value. This review briefly summarizes the means by which inositide functions have been pharmacologically manipulated, and discusses possibilities for specifically targeting certain aspects of their regulatory functions. JF - Current Pharmaceutical Design AU - Balla, T AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA, tambal@box-t.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 475 EP - 507 VL - 7 IS - 6 SN - 1381-6128, 1381-6128 KW - phosphoinositides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Drug discovery KW - Reviews KW - Pharmaceuticals KW - Phospholipids KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18070409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Design&rft.atitle=Pharmacology+of+Phosphoinositides%2C+Regulators+of+Multiple+Cellular+Functions&rft.au=Balla%2C+T&rft.aulast=Balla&rft.aufirst=T&rft.date=2001-04-01&rft.volume=7&rft.issue=6&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Current+Pharmaceutical+Design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pharmaceuticals; Drug discovery; Phospholipids; Reviews ER - TY - JOUR T1 - Earlier plant flowering in spring as a response to global warming in the Washington, DC, area AN - 17888810; 5125842 AB - Evidence for global warming is inferred from spring advances in first-flowering in plants. The trend of average first-flowering times per year for the study group shows a significant advance of 2.4 days over a 30-year period. When 11 species that exhibit later first-flowering times are excluded from the data set, the remaining 89 show a significant advance of 4.5 days. Significant trends for earlier-flowering species range from -3.2 to -46 days, while those for later-flowering species range from +3.1 to +10.4 days. Advances of first-flowering in these 89 species are directly correlated with local increase in minimum temperature (T sub(min)). JF - Biodiversity and Conservation AU - Abu-Asab AU - Peterson, P M AU - Shetler, S G AU - Orli, S S AD - Section of Ultrastructural Pathology, Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 597 EP - 612 VL - 10 IS - 4 SN - 0960-3115, 0960-3115 KW - Washington, D.C. KW - USA, District of Columbia KW - Ecology Abstracts KW - Flowering KW - Phenology KW - Annual variations KW - Plants KW - Global warming KW - D 04625:Plants - general UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17888810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biodiversity+and+Conservation&rft.atitle=Earlier+plant+flowering+in+spring+as+a+response+to+global+warming+in+the+Washington%2C+DC%2C+area&rft.au=Abu-Asab%3BPeterson%2C+P+M%3BShetler%2C+S+G%3BOrli%2C+S+S&rft.aulast=Abu-Asab&rft.aufirst=&rft.date=2001-04-01&rft.volume=10&rft.issue=4&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Biodiversity+and+Conservation&rft.issn=09603115&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Annual variations; Phenology; Plants; Flowering; Global warming ER - TY - JOUR T1 - Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro AN - 17886380; 5123593 AB - Respiratory syncytial virus (RSV) is an important human pathogen that can cause severe and life-threatening respiratory infections in infants and immunocompromised adults. We have recently shown that the RSV F glycoprotein, which mediates viral fusion, binds to RhoA. One of the steps in RhoA activation involves isoprenylation at the carboxy terminus of the protein by geranylgeranyltransferase. This modification allows RhoA to be attached to phosphatidyl serine on the inner leaflet of the plasma membrane. Treatment of mice with lovastatin, a drug that inhibits prenylation pathways in the cell by directly inhibiting hydroxymethylglutaryl coenzyme A reductase, diminishes RSV but not vaccinia virus replication when administered up to 24 h after RSV infection and decreases virus-induced weight loss and illness in mice. The inhibition of replication is not likely due to the inhibition of cholesterol biosynthesis, since gemfibrozil, another cholesterol-lowering agent, did not affect virus replication and serum cholesterol levels were not significantly lowered by lovastatin within the time frame of the experiment. Lovastatin also reduces cell-to-cell fusion in cell culture and eliminates RSV replication in HEp-2 cells. These data indicate that lovastatin, more specific isoprenylation inhibitors, or other pharmacological approaches for preventing RhoA membrane localization should be considered for evaluation as a preventive antiviral therapy for selected groups of patients at high risk for severe RSV disease, such as the institutionalized elderly and bone marrow or lung transplant recipients. JF - Antimicrobial Agents & Chemotherapy AU - Gower, T L AU - Graham, B S AD - A-4103 MCN, Vanderbilt University School of Medicine, 1161 21st Ave. South, Nashville, TN 37232-2582, USA, bgraham@mail.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 1231 EP - 1237 VL - 45 IS - 4 SN - 0066-4804, 0066-4804 KW - animal models KW - mice KW - Geranylgeranyltransferase KW - Lovastatin KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Respiratory syncytial virus KW - Termination KW - Respiratory tract diseases KW - Antiviral agents KW - A 01068:Antiviral & viricidal KW - V 22150:Animal models & experimentally-induced viral infections KW - V 22100:Antiviral agents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17886380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Antiviral+activity+of+lovastatin+against+respiratory+syncytial+virus+in+vivo+and+in+vitro&rft.au=Gower%2C+T+L%3BGraham%2C+B+S&rft.aulast=Gower&rft.aufirst=T&rft.date=2001-04-01&rft.volume=45&rft.issue=4&rft.spage=1231&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Respiratory syncytial virus; Respiratory tract diseases; Antiviral agents; Termination ER - TY - JOUR T1 - The AraC transcriptional activators AN - 17883418; 5123656 AB - The AraC family of bacterial transcriptional activators regulate diverse genetic systems. Recent X-ray diffraction studies show that the monomeric MarA and Rob activators bind to their asymmetric degenerate DNA sites via two different helix-turn-helix elements. Activation by MarA, SoxS or Rob requires a particular orientation of the asymmetric binding sequence (and hence the activator), depending on its distance from the -10 RNAP signal. Genetic studies are beginning to clarify how the activators interact with RNAP. Growing evidence suggests that for the sugar metabolism activators, multiple binding sites upstream of the promoter anchor the activator in a repressing or nonactivating configuration. By interaction with the sugar and/or CRP, the activator is allosterically altered so it can bind a new set of sites that enable it to activate the promoter. Surprisingly, the virulence activator, Rns, must bind to both upstream and downstream sites in order to activate the rns promoter. JF - Current Opinion in Microbiology AU - Martin, R G AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, USA, rgmartin@helix.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 132 EP - 137 VL - 4 IS - 2 SN - 1369-5274, 1369-5274 KW - AraC protein KW - rns promoter KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-directed RNA polymerase KW - DNA KW - Transcription KW - X-ray diffraction KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17883418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Microbiology&rft.atitle=The+AraC+transcriptional+activators&rft.au=Martin%2C+R+G%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=2001-04-01&rft.volume=4&rft.issue=2&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Transcription; DNA; X-ray diffraction; DNA-directed RNA polymerase ER - TY - JOUR T1 - 14-Week toxicity and cell proliferation of methyleugenol administered by gavage to F344 rats and B6C3F1 mice AN - 17870192; 5118964 AB - Methyleugenol, a food flavor and fragrance agent, was tested for toxicity in male and female F344/N rats and B6C3F1 mice. Groups of 10 males and 10 females per sex per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14 weeks. Additional groups of rats and mice of each sex were dosed similarly and used for hematology and clinical chemistry studies. Groups of 10 male and 10 female rats and mice received the vehicle by gavage on the same dosing schedule and served as vehicle controls. For serum gastrin, gastric pH and cell proliferation studies groups of 10 female rats were given 0, 37, 75 or 150 mg/kg, once daily 5 days per week for 30 or 90 days or 300 or 1000 mg/kg for 30 days; male mice were given 0, 9, 18.5, 37, 75, 150 or 300 mg/kg for 30 or 90 days. For the gastrin, pH and cell proliferation studies, groups of 10 female rats and 10 male mice were given the vehicle for 30 or 90 days and served as controls. Methyleugenol administration to rats induced erythrocyte microcytosis and thrombocytosis in male and female rats. It also caused an increase in serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentration, suggesting hepatocellular injury, cholestasis or altered hepatic function. Additionally, methyleugenol induced hypoproteinemia and hypoalbuminemia, evidenced by decreased total protein and albumin concentrations in both male and female rats, suggesting in inefficiency of dietary protein utilization due to methyleugenol-induced toxic effects on the liver and glandular stomach of rats and mice. The increase in gastrin and gastric pH of rats and mice given methyleugenol suggests that gastrin feedback was impaired and resulted in conditions not conducive to protein digestion. In rats, methyleugenol caused an increase in the incidences of hepatocyte cytologic alteration, cytomegaly, Kupffer cell pigmentation, mixed foci of cellular alteration and bile duct hyperplasia of the liver and atrophy and chronic inflammation of the mucosa of the glandular stomach. In mice, it caused an increase in the incidence of cytologic alteration, necrosis, bile duct hyperplasia and subacute inflammation of the liver and atrophy, degeneration, necrosis, edema, mitotic alteration, and cystic glands of the fundic region of the glandular stomach. The increased incidences of adrenal gland cortical hypertrophy and/or cytoplasmic alteration in the submandibular salivary glands, adrenal glands, testis and uterus of rats were considered secondary to the chemical-related effects observed in the liver and glandular stomach. Based on mortality, body weight gain, clinical chemistry and gross and microscopic evaluation of tissues of rats and mice, the no-observed-effect level (NOEL) of methyleugenol for both species was estimated at 10 mg/kg. JF - Food and Chemical Toxicology AU - Abdo, K M AU - Cunningham, M L AU - Snell, M L AU - Herbert, R A AU - Travlos, G S AU - Eldridge AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 303 EP - 316 VL - 39 IS - 4 SN - 0278-6915, 0278-6915 KW - rats KW - mice KW - methyleugenol KW - Toxicology Abstracts KW - Food additives KW - Liver KW - Gastrin KW - Flavorings KW - Cell proliferation KW - Fragrances KW - Stomach KW - X 24140:Cosmetics, toiletries & household products KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17870192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+Chemical+Toxicology&rft.atitle=14-Week+toxicity+and+cell+proliferation+of+methyleugenol+administered+by+gavage+to+F344+rats+and+B6C3F1+mice&rft.au=Abdo%2C+K+M%3BCunningham%2C+M+L%3BSnell%2C+M+L%3BHerbert%2C+R+A%3BTravlos%2C+G+S%3BEldridge%3BBucher%2C+J+R&rft.aulast=Abdo&rft.aufirst=K&rft.date=2001-04-01&rft.volume=39&rft.issue=4&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Food+and+Chemical+Toxicology&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Flavorings; Stomach; Gastrin; Liver; Food additives; Fragrances; Cell proliferation ER - TY - JOUR T1 - Lineage-Specific Gene Expansions in Bacterial and Archaeal Genomes AN - 17864914; 5107952 AB - Gene duplication is an important mechanistic antecedent to the evolution of new genes and novel biochemical functions. In an attempt to assess the contribution of gene duplication to genome evolution in archaea and bacteria, clusters of related genes that appear to have expanded subsequent to the diversification of the major prokaryotic lineages (lineage-specific expansions) were analyzed. Analysis of 21 completely sequenced prokaryotic genomes shows that lineage-specific expansions comprise a substantial fraction ( similar to 5%-33%) of their coding capacities. A positive correlation exists between the fraction of the genes taken up by lineage-specific expansions and the total number of genes in a genome. Consistent with the notion that lineage-specific expansions are made up of relatively recently duplicated genes, >90% of the detected clusters consists of only two to four genes. The more common smaller clusters tend to include genes with higher pairwise similarity (as reflected by average score density) than larger clusters. Regardless of size, cluster members tend to be located more closely on bacterial chromosomes than expected by chance, which could reflect a history of tandem gene duplication. In addition to the small clusters, almost all genomes also contain rare large clusters of size greater than or equal to 20. Several examples of the potential adaptive significance of these large clusters are explored. The presence or absence of clusters and their related genes was used as the basis for the construction of a similarity graph for completely sequenced prokaryotic genomes. The topology of the resulting graph seems to reflect a combined effect of common ancestry, horizontal transfer, and lineage-specific gene loss. JF - Genome Research AU - Jordan, I K AU - Makarova, K S AU - Spouge, J L AU - Wolf, YI AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 555 EP - 565 VL - 11 IS - 4 SN - 1054-9803, 1054-9803 KW - Bacteria KW - gene duplication KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Genomes KW - Archaea KW - Gene transfer KW - Gene clusters KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17864914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+Research&rft.atitle=Lineage-Specific+Gene+Expansions+in+Bacterial+and+Archaeal+Genomes&rft.au=Jordan%2C+I+K%3BMakarova%2C+K+S%3BSpouge%2C+J+L%3BWolf%2C+YI%3BKoonin%2C+E+V&rft.aulast=Jordan&rft.aufirst=I&rft.date=2001-04-01&rft.volume=11&rft.issue=4&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10549803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Archaea; Bacteria; Gene clusters; Gene transfer; Genomes ER - TY - JOUR T1 - The Peptide Near the C Terminus Regulates Receptor CAR Nuclear Translocation Induced by Xenochemicals in Mouse Liver AN - 17831333; 4864460 AB - In response to phenobarbital (PB) and other PB- type inducers, the nuclear receptor CAR translocates to the mouse liver nucleus (T. Kawamoto et al., Mol. Cell. Biol. 19:6318-6322, 1999). To define the translocation mechanism, fluorescent protein-tagged human CAR (hCAR) was expressed in the mouse livers using the in situ DNA injection and gene delivery systems. As in the wild-type hCAR, the truncated receptor lacking the C-terminal 10 residues (i.e., AF2 domain) translocated to the nucleus, indicating that the PB-inducible translocation is AF2 independent. Deletion of the 30 C-terminal residues abolished the receptor translocation, and subsequent site-directed mutagenesis delineated the PB-inducible translocation activity of the receptor to the peptide L super(313)GLL super(316)AEL super(319). Ala mutations of Leu313, Leu316, or Leu319 abrogated the translocation of CAR in the livers, while those of Leu312 or Leu315 did not affect the nuclear translocation. The leucine-rich peptide dictates the nuclear translocation of hCAR in response to various PB-type inducers and appears to be conserved in the mouse and rat receptors. JF - Molecular and Cellular Biology AU - Zelko, I AU - Sueyoshi, T AU - Kawamoto, T AU - Moore, R AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, negishi@niehs.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 2838 EP - 2846 PB - American Society for Microbiology VL - 21 IS - 8 SN - 0270-7306, 0270-7306 KW - transport KW - mice KW - CAR receptors KW - Toxicology Abstracts KW - Liver KW - Xenobiotics KW - Nuclei KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17831333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Cellular+Biology&rft.atitle=The+Peptide+Near+the+C+Terminus+Regulates+Receptor+CAR+Nuclear+Translocation+Induced+by+Xenochemicals+in+Mouse+Liver&rft.au=Zelko%2C+I%3BSueyoshi%2C+T%3BKawamoto%2C+T%3BMoore%2C+R%3BNegishi%2C+M&rft.aulast=Zelko&rft.aufirst=I&rft.date=2001-04-01&rft.volume=21&rft.issue=8&rft.spage=2838&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Xenobiotics; Nuclei; Liver ER - TY - JOUR T1 - Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Replication by HIV-1-Based Lentivirus Vectors Expressing Transdominant Rev AN - 17820313; 4860816 AB - Retrovirus vectors expressing transdominant-negative mutants of Rev (TdRev) inhibit human immunodeficiency virus type 1 (HIV-1) replication by preventing the nuclear export of unspliced viral transcripts, thus inhibiting the synthesis of Gag-Pol, Env, and genomic RNA. The use of HIV-1-based vectors to express TdRev would have the advantage of allowing access to nondividing hematopoietic cells. It would also provide additional levels of protection by sequestering the viral regulatory proteins Tat and Rev, competing for encapsidation into wild-type virions, and inhibiting reverse transcription. Here we describe HIV-1-based vectors that express TdRev. These vectors contain mutations in the splicing signals or replacement of the Rev-responsive element by the simian retrovirus type 1 constitutive transport element, making them less sensitive to the inhibitory effects of TdRev. In addition, overexpression of Rev and the use of an HIV-1 helper plasmid that drives high levels of Gag-Pol synthesis were used to transiently overcome the inhibition by TdRev of the synthesis of Gag-Pol during vector production. SupT1 cells transduced with these vectors were more resistant to HIV-1 replication than cells transduced with Moloney murine leukemia virus-based vectors expressing TdRev. Furthermore, we show that these vectors can be mobilized by the wild-type virus, reducing the infectivity of virions escaping inhibition and conferring protection against HIV-1 replication to previously untransduced cells. JF - Journal of Virology AU - Mautino, M R AU - Keiser, N AU - Morgan, R A AD - Clinical Gene Therapy Branch, NHGRI, 10 Center Dr., Building 10, Room 10C103, Bethesda, MD 20892-1851, rmorgan@nhgri.nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 3590 EP - 3599 PB - American Society for Microbiology VL - 75 IS - 8 SN - 0022-538X, 0022-538X KW - HIV-1 KW - Human immunodeficiency virus 1 KW - Rev gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Expression vectors KW - Replication KW - Inhibition KW - Mutants KW - Reverse transcription KW - W3 33181:Gene therapy vectors KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17820313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Statistics+Education&rft.atitle=The+Effect+of+Distributed+Practice+in+Undergraduate+Statistics+Homework+Sets%3A+A+Randomized+Trial&rft.au=Crissinger%2C+Bryan+R.&rft.aulast=Crissinger&rft.aufirst=Bryan&rft.date=2015-01-01&rft.volume=23&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+Statistics+Education&rft.issn=E10691898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Expression vectors; Inhibition; Replication; Reverse transcription; Mutants DO - http://dx.doi.org/10.1128/JVI.75.8.3590-3599.2001 ER - TY - JOUR T1 - Physiological Basis for Conservation of the Signal Recognition Particle Targeting Pathway in Escherichia coli AN - 17816301; 4860072 AB - The Escherichia coli signal recognition particle (SRP) is a ribonucleoprotein complex that targets nascent inner membrane proteins (IMPs) to transport sites in the inner membrane (IM). Since SRP depletion only partially inhibits IMP insertion under some growth conditions, however, it is not clear why the particle is absolutely essential for viability. Insights into this question emerged from experiments in which we analyzed the physiological consequences of reducing the intracellular concentration of SRP below the wild-type level. We found that even moderate SRP deficiencies that have little effect on cell growth led to the induction of a heat shock response. Genetic manipulations that suppress the heat shock response were lethal in SRP-deficient cells, indicating that the elevated synthesis of heat shock proteins plays an important role in maintaining cell viability. Although it is conceivable that the heat shock response serves to increase the capacity of cells to target IMPs via chaperone-based mechanisms, SRP-deficient cells did not show an increased dependence on either GroEL or DnaK. By contrast, the heat shock-regulated proteases Lon and ClpQ became essential for viability when SRP levels were reduced. These results suggest that the heat shock response protects SRP-deficient cells by increasing their capacity to degrade mislocalized IMPs. Consistent with this notion, a model IMP that was mislocalized in the cytoplasm as the result of SRP depletion appeared to be more stable in a Delta lon Delta clpQ strain than in control cells. Taken together, the data provide direct evidence that SRP is essential in E. coli and possibly conserved throughout prokaryotic evolution as well partly because efficient IMP targeting prevents a toxic accumulation of aggregated proteins in the cytoplasm. JF - Journal of Bacteriology AU - Bernstein, H D AU - Hyndman, J B AD - National Institutes of Health, Building 10, Room 9D-20, Bethesda, MD 20892- 1810, harris_bernstein@nih.gov Y1 - 2001/04// PY - 2001 DA - Apr 2001 SP - 2187 EP - 2197 VL - 183 IS - 7 SN - 0021-9193, 0021-9193 KW - IMP targeting KW - ClpQ protein KW - Lon protein KW - ribonucleoproteins KW - signal recognition particle KW - Microbiology Abstracts B: Bacteriology KW - Inner membranes KW - Escherichia coli KW - Heat shock KW - Membrane proteins KW - Evolution KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17816301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Physiological+Basis+for+Conservation+of+the+Signal+Recognition+Particle+Targeting+Pathway+in+Escherichia+coli&rft.au=Bernstein%2C+H+D%3BHyndman%2C+J+B&rft.aulast=Bernstein&rft.aufirst=H&rft.date=2001-04-01&rft.volume=183&rft.issue=7&rft.spage=2187&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.183.7.2187-2197.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Inner membranes; Membrane proteins; Heat shock; Evolution DO - http://dx.doi.org/10.1128/JB.183.7.2187-2197.2001 ER - TY - JOUR T1 - New models for assessing carcinogenesis: an ongoing process. AN - 70811122; 11323177 AB - Traditionally, the use of rodent models in assessing the carcinogenic potential of chemicals has been expensive and lengthy, and the relevance of the carcinogenic effect to humans is often not fully understood. Today, however, with the rapid advances in molecular biology, genetically altered mice containing genes relevant to humans (e.g. oncogenes, tumor suppressor genes) and reporter genes (e.g. lacI) provide powerful tools for examining specific chemical-gene interactions thereby allowing a better understanding of the mechanisms of carcinogenesis in a shorter period of time. This paper will cover an overview of ongoing validation efforts, followed by examples of studies using several genetically engineered models including the p53def mouse model and the Big Blue transgenic mouse model. Specifically, examples where transgenic models were integrated into the testing program based on specific hypotheses dealing with genetic alterations in cancer genes and reporter genes will be discussed. The examples will highlight possible ways genetically altered mice may be integrated into a comprehensive research and testing strategy and thereby provide an improved estimation of human health risks. JF - Toxicology letters AU - Sills, R C AU - French, J E AU - Cunningham, M L AD - Laboratory of Experimental Pathology, MD: B3-08, National Institute Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. sills@niehs.nih.gov Y1 - 2001/03/31/ PY - 2001 DA - 2001 Mar 31 SP - 187 EP - 198 VL - 120 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Bacterial Proteins KW - 0 KW - Butadienes KW - Carcinogens KW - Escherichia coli Proteins KW - Lac Repressors KW - Repressor Proteins KW - Benzo(a)pyrene KW - 3417WMA06D KW - Urethane KW - 3IN71E75Z5 KW - Oxazepam KW - 6GOW6DWN2A KW - Phenolphthalein KW - 6QK969R2IF KW - Benzene KW - J64922108F KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Animals KW - Bacterial Proteins -- genetics KW - Oxazepam -- toxicity KW - Butadienes -- toxicity KW - Benzo(a)pyrene -- toxicity KW - Benzene -- toxicity KW - Phenolphthalein -- toxicity KW - Mice KW - Urethane -- toxicity KW - Mice, Transgenic KW - Repressor Proteins -- genetics KW - Models, Animal KW - Genes, p53 -- physiology KW - Carcinogens -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70811122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=New+models+for+assessing+carcinogenesis%3A+an+ongoing+process.&rft.au=Sills%2C+R+C%3BFrench%2C+J+E%3BCunningham%2C+M+L&rft.aulast=Sills&rft.aufirst=R&rft.date=2001-03-31&rft.volume=120&rft.issue=1-3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic variability in susceptibility and response to toxicants. AN - 70810305; 11323185 AB - Everyone has a unique combination of polymorphic traits that modify susceptibility and response to drugs, chemicals and carcinogenic exposures. The metabolism of exogenous and endogenous chemical toxins may be modified by inherited and induced variation in CYP (P450), acetyltransferase (NAT) and glutathione S-transferase (GST) genes. We observe that specific 'at risk' genotypes for GSTM1 and NAT1/2 increase risk for bladder cancer among smokers. Genotypic and phenotypic variation in DNA repair may affect risk of somatic mutation and cancer. Variants of base excision and nucleotide excision repair genes (XRCC1 and XPD) appear to modify exposure-induced damage from cigarette smoke and radiation. We are currently engaged in discovering genetic variation in environmental response genes and determining if this variation has any effect on gene function or if it is associated with disease risk. These and other results are discussed in the context of evaluating inherited or acquired susceptibility risk factors for environmentally caused disease. JF - Toxicology letters AU - Miller, M C AU - Mohrenweiser, H W AU - Bell, D A AD - National Institute of Environmental Health Sciences, 111 Alexander Drive, Building 101, Room B323, P.O. Box 12233, C3-03, Research Triangle Park, NC 27709, USA. Y1 - 2001/03/31/ PY - 2001 DA - 2001 Mar 31 SP - 269 EP - 280 VL - 120 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Carcinogens KW - 0 KW - Xenobiotics KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Acetyltransferases KW - EC 2.3.1.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Environment KW - DNA Repair KW - Carcinogens -- metabolism KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Humans KW - Carcinogens -- toxicity KW - Glutathione Transferase -- genetics KW - Acetyltransferases -- genetics KW - Genomics KW - Xenobiotics -- metabolism KW - Xenobiotics -- toxicity KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70810305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Genetic+variability+in+susceptibility+and+response+to+toxicants.&rft.au=Miller%2C+M+C%3BMohrenweiser%2C+H+W%3BBell%2C+D+A&rft.aulast=Miller&rft.aufirst=M&rft.date=2001-03-31&rft.volume=120&rft.issue=1-3&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of gene knockout mice to unravel the mechanisms of toxicity and chemical carcinogenesis. AN - 70798551; 11323178 AB - Metabolism of toxins and carcinogens is carried out by large groups of xenobiotic-metabolizing enzymes. These enzymes are generally considered to be required for elimination of xenobiotics such as drugs, dietary chemicals and environmental pollutants, and to be required for chemical toxicity and carcinogenicity. An important role for these enzymes in metabolism of endogenous chemicals has not been established. Mouse lines in which the genes encoding several xenobiotic-metabolizing enzymes were knocked out were produced and are being used to determine the role of metabolism in carcinogenesis, and acute and chronic toxicities in vivo. Mouse lines lacking the P450s CYP1A1, CYP1A2, CYP1B1 and CYP2E1, microsomal epoxide hydrolase (mEH), NADPH:quinone oxidoreductase and the glutathione S-transferase P1 have no deleterious phenotypes, indicating that these enzymes are not required for mammalian development and physiological homeostasis. However, when challenged with toxins and carcinogens, they respond differently from their wild-type (WT) counterparts. For example, mice lacking CYP1A2 and CYP2E1 are totally resistant to acetaminophen-induced hepatotoxicity. Mice lacking CYP1B1 or mEH are less responsive to tumorigenesis by 7,12-dimethybenz[a]anthracene. However, CYP1A2-null mice do not significantly differ from WT mice in their response to the hepatocarcinogen 4-aminobiphenyl. These and other studies indicate that the xenobiotic-metabolism null mice are of great value in the study of the mechanisms of chemical injury. JF - Toxicology letters AU - Gonzalez, F J AD - Division of Basic Sciences, National Cancer Institute, Building 37, Room 3E-24, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2001/03/31/ PY - 2001 DA - 2001 Mar 31 SP - 199 EP - 208 VL - 120 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Carcinogens KW - 0 KW - Xenobiotics KW - Acetaminophen KW - 362O9ITL9D KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp1b1 protein, mouse KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Cytochrome P-450 CYP1A2 -- physiology KW - Animals KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Xenobiotics -- metabolism KW - Mice KW - Cytochrome P-450 CYP2E1 -- physiology KW - Carbon Tetrachloride -- toxicity KW - Cytochrome P-450 CYP1A1 -- physiology KW - Acetaminophen -- toxicity KW - Mice, Knockout KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70798551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=The+use+of+gene+knockout+mice+to+unravel+the+mechanisms+of+toxicity+and+chemical+carcinogenesis.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=2001-03-31&rft.volume=120&rft.issue=1-3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of mutant amyloid precursor proteins decreases adhesion and delays differentiation of Hep-1 cells. AN - 77013579; 11277983 AB - The amyloid precursor protein (APP) is a type I integral membrane protein and is processed to generate several intra-cellular and secreted fragments. The physiological role of APP and its processed fragments is unclear. Several mutations have been discovered in APP, which are causative of early-onset, familial, neurological disease, including Alzheimer's disease (FAD). These mutations alter the processing of APP and lead to excess production and extra-cellular deposition of A-beta peptide (Abeta). We have examined the role of APP in a cell culture model of endothelial cell function. The endothelial cell line, Hep-1, was stably transfected with wild-type (wt) and FAD mutant forms of APP (mAPP). Secretion of sAPPalpha was reduced in cell lines over-expressing mAPP when these cells were grown on several different substrates. Levels of secreted Abeta were increased as measured by ELISA in the mutant cell lines. Cell adhesion to laminin-, fibronectin-, collagen I-, and collagen IV-coated culture flasks was reduced in all mAPP-expressing cell lines, while in lines over-expressing wt-APP, adhesiveness was slightly increased. Cell lines over-expressing mAPP differentiated more slowly into capillary network-like structures on Matrigel than those expressing wt-APP. No differences were detected among all cell lines in a migration/invasion assay. The results suggest that APP may have a role in cell adhesiveness and maturation of endothelial cells into capillary-like networks. The reduction in adhesion and differentiation in mutant cell lines may be due to reduced amounts of sAPPalpha released into the culture media or toxic effects of increased extracellular Abeta. JF - Brain research AU - Kusiak, J W AU - Lee, L L AU - Zhao, B AD - Molecular Neurobiology Unit, Laboratory of Cellular and Molecular Biology, Intramural Research Program, Gerontology Research Center, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. kusiak@vax.grc.nia.hin.gov Y1 - 2001/03/30/ PY - 2001 DA - 2001 Mar 30 SP - 146 EP - 152 VL - 896 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Amyloid beta-Protein Precursor KW - 0 KW - Biocompatible Materials KW - Drug Combinations KW - Fibronectins KW - Laminin KW - Proteoglycans KW - matrigel KW - 119978-18-6 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Cell Adhesion -- physiology KW - Humans KW - Mutagenesis -- physiology KW - Signal Transduction -- physiology KW - Tumor Cells, Cultured KW - Cell Differentiation -- physiology KW - Transfection KW - Cell Movement -- physiology KW - Amyloidosis -- pathology KW - Gene Expression -- physiology KW - Alzheimer Disease -- pathology KW - Liver -- cytology KW - Amyloid beta-Protein Precursor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77013579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Expression+of+mutant+amyloid+precursor+proteins+decreases+adhesion+and+delays+differentiation+of+Hep-1+cells.&rft.au=Kusiak%2C+J+W%3BLee%2C+L+L%3BZhao%2C+B&rft.aulast=Kusiak&rft.aufirst=J&rft.date=2001-03-30&rft.volume=896&rft.issue=1-2&rft.spage=146&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interacting fidelity defects in the replicative DNA polymerase of bacteriophage RB69. AN - 76996015; 11133987 AB - The DNA polymerases (gp43s) of the related bacteriophages T4 and RB69 are B family (polymerase alpha class) enzymes that determine the fidelity of phage DNA replication. A T4 whose gene 43 has been mutationally inactivated can be replicated by a cognate RB69 gp43 encoded by a recombinant plasmid in T4-infected Escherichia coli. We used this phage-plasmid complementation assay to obtain rapid and sensitive measurements of the mutational specificities of mutator derivatives of the RB69 enzyme. RB69 gp43s lacking proofreading function (Exo(-) enzymes) and/or substituted with alanine, serine, or threonine at the conserved polymerase function residue Tyr(567) (Pol(Y567(A/S/T)) enzymes) were examined for their effects on the reversion of specific mutations in the T4 rII gene and on forward mutation in the T4 rI gene. The results reveal that Tyr(567) is a key determinant of the fidelity of base selection and that the Pol and Exo functions are strongly coupled in this B family enzyme. In vitro assays show that the Pol(Y567A) Exo(-) enzyme generates mispairs more frequently but extends them less efficiently than does a Pol(+) Exo(-) enzyme. Other replicative DNA polymerases may control fidelity by strategies similar to those used by RB69 gp43. JF - The Journal of biological chemistry AU - Bebenek, A AU - Dressman, H K AU - Carver, G T AU - Ng , S AU - Petrov, V AU - Yang, G AU - Konigsberg, W H AU - Karam, J D AU - Drake, J W AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2001/03/30/ PY - 2001 DA - 2001 Mar 30 SP - 10387 EP - 10397 VL - 276 IS - 13 SN - 0021-9258, 0021-9258 KW - Viral Proteins KW - 0 KW - gene 43 protein, Enterobacteria phage T4 KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Alanine KW - OF5P57N2ZX KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Plasmids -- metabolism KW - Escherichia coli -- metabolism KW - Sequence Homology, Nucleic Acid KW - Alanine -- chemistry KW - Viral Proteins -- physiology KW - Serine -- chemistry KW - Cloning, Molecular KW - Mutagenesis KW - Thymidine -- metabolism KW - Alleles KW - Base Sequence KW - Threonine -- chemistry KW - Chromatography, Gel KW - Kinetics KW - Genetic Complementation Test KW - Molecular Sequence Data KW - Viral Proteins -- metabolism KW - Time Factors KW - Mutation KW - Cell Division KW - Bacteriophages -- enzymology KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76996015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Interacting+fidelity+defects+in+the+replicative+DNA+polymerase+of+bacteriophage+RB69.&rft.au=Bebenek%2C+A%3BDressman%2C+H+K%3BCarver%2C+G+T%3BNg+%2C+S%3BPetrov%2C+V%3BYang%2C+G%3BKonigsberg%2C+W+H%3BKaram%2C+J+D%3BDrake%2C+J+W&rft.aulast=Bebenek&rft.aufirst=A&rft.date=2001-03-30&rft.volume=276&rft.issue=13&rft.spage=10387&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions among drugs for HIV and opportunistic infections. AN - 76968087; 11274626 JF - The New England journal of medicine AU - Piscitelli, S C AU - Gallicano, K D AD - Department of Pharmacy, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/03/29/ PY - 2001 DA - 2001 Mar 29 SP - 984 EP - 996 VL - 344 IS - 13 SN - 0028-4793, 0028-4793 KW - Anti-Infective Agents KW - 0 KW - HIV Protease Inhibitors KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - Reverse Transcriptase Inhibitors KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Abridged Index Medicus KW - Index Medicus KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- pharmacology KW - Humans KW - Drug Monitoring KW - Absorption KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- therapeutic use KW - Cytochrome P-450 Enzyme System -- drug effects KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Reverse Transcriptase Inhibitors -- metabolism KW - Anti-Infective Agents -- therapeutic use KW - Drug Interactions KW - Anti-Infective Agents -- metabolism KW - Reverse Transcriptase Inhibitors -- pharmacology KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- pharmacology KW - HIV Protease Inhibitors -- therapeutic use KW - Anti-Infective Agents -- pharmacology KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76968087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Interactions+among+drugs+for+HIV+and+opportunistic+infections.&rft.au=Piscitelli%2C+S+C%3BGallicano%2C+K+D&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=2001-03-29&rft.volume=344&rft.issue=13&rft.spage=984&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial cytochrome c oxidase subunit III is selectively down-regulated by aluminum exposure in PC12S cells. AN - 77002359; 11277571 AB - Aluminum (Al) has been implicated in several neurological diseases including dialysis dementia and Alzheimer's disease (AD). One possible mechanism of Al neurotoxicity could involve alteration of mitochondrial gene expression. We exposed PC12 cells to 0.1-100 microM AlCl3 for 6h at pH 7.4. Internalized Al, measured by atomic absorption spectrometry, was linearly proportional to the extracellular Al concentration. Northern blot analyses showed that cytochrome c oxidase subunit III (COX III) mRNA was significantly reduced by 70% after addition of 1 microM AlCl3. Higher concentrations of AlCl3 did not show a significant further effect. These results suggest that Al neurotoxicity involves a specific impairment of cytochrome c oxidase. JF - Neuroreport AU - Bosetti, F AU - Solaini, G AU - Tendi, E A AU - Chikhale, E G AU - Chandrasekaran, K AU - Rapoport, S I AD - Section on Brain Physiology and Metabolism, National Institute on Aging, NIH, Bethesda, MD 20892, USA. Y1 - 2001/03/26/ PY - 2001 DA - 2001 Mar 26 SP - 721 EP - 724 VL - 12 IS - 4 SN - 0959-4965, 0959-4965 KW - Aluminum Compounds KW - 0 KW - Astringents KW - Chlorides KW - RNA, Messenger KW - RNA, Ribosomal KW - RNA, ribosomal, 12S KW - aluminum chloride KW - 3CYT62D3GA KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Electron Transport Complex I KW - EC 1.6.5.3 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Index Medicus KW - Rats KW - Animals KW - NADH, NADPH Oxidoreductases -- genetics KW - Cell Survival -- drug effects KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Dose-Response Relationship, Drug KW - RNA, Ribosomal -- genetics KW - RNA, Messenger -- analysis KW - Enzyme Activation -- drug effects KW - Alzheimer Disease -- metabolism KW - PC12 Cells KW - Electron Transport Complex IV -- genetics KW - Chlorides -- toxicity KW - Aluminum Compounds -- pharmacokinetics KW - Neurons -- drug effects KW - Mitochondria -- enzymology KW - Neurons -- cytology KW - Aluminum Compounds -- toxicity KW - Electron Transport Complex IV -- metabolism KW - Chlorides -- pharmacokinetics KW - Astringents -- toxicity KW - Astringents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77002359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Mitochondrial+cytochrome+c+oxidase+subunit+III+is+selectively+down-regulated+by+aluminum+exposure+in+PC12S+cells.&rft.au=Bosetti%2C+F%3BSolaini%2C+G%3BTendi%2C+E+A%3BChikhale%2C+E+G%3BChandrasekaran%2C+K%3BRapoport%2C+S+I&rft.aulast=Bosetti&rft.aufirst=F&rft.date=2001-03-26&rft.volume=12&rft.issue=4&rft.spage=721&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression profiling of acetaminophen liver toxicity in mice using microarray technology. AN - 76997968; 11264010 AB - Drug-induced hepatotoxicity causes significant morbidity and mortality and is a major concern in drug development. This is due, in large part, to insufficient knowledge of the mechanism(s) of drug-induced liver injury. In order to address this problem, we have evaluated the modulation of gene expression within the livers of mice treated with a hepatotoxic dose of acetaminophen (APAP) using high-density oligonucleotide microarrays capable of determining the expression profile of >11,000 genes and expressed sequence tags (ESTs). Significant alterations in gene expression, both positive and negative, were noted within the livers of APAP-treated mice. APAP-induced toxicity affected numerous aspects of liver physiology causing, for instance, >twofold increased expression of genes that encode for growth arrest and cell cycle regulatory proteins, stress-induced proteins, the transcription factor LRG-21, suppressor of cytokine signaling (SOCS)-2-protein, and plasminogen activator inhibitor-1 (PAI-1). A number of these and other genes and ESTs were detectable within the liver only after APAP treatment suggesting their potential importance in propagating or preventing further toxicity. These data provide new directions for mechanistic studies that may lead to a better understanding of the molecular basis of drug-induced liver injury and, ultimately, to a more rational design of safer drugs. Copyright 2001 Academic Press. JF - Biochemical and biophysical research communications AU - Reilly, T P AU - Bourdi, M AU - Brady, J N AU - Pise-Masison, C A AU - Radonovich, M F AU - George, J W AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, National Institutes of Health, Bethesda, Maryland, USA. ReillyT@nhlbi.nih.gov Y1 - 2001/03/23/ PY - 2001 DA - 2001 Mar 23 SP - 321 EP - 328 VL - 282 IS - 1 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Mice KW - Gene Expression Profiling KW - Oligonucleotide Array Sequence Analysis KW - Liver -- drug effects KW - Liver -- metabolism KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76997968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Expression+profiling+of+acetaminophen+liver+toxicity+in+mice+using+microarray+technology.&rft.au=Reilly%2C+T+P%3BBourdi%2C+M%3BBrady%2C+J+N%3BPise-Masison%2C+C+A%3BRadonovich%2C+M+F%3BGeorge%2C+J+W%3BPohl%2C+L+R&rft.aulast=Reilly&rft.aufirst=T&rft.date=2001-03-23&rft.volume=282&rft.issue=1&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Biochem Biophys Res Commun 2001 May 4;283(2):536 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. AN - 76983577; 11096081 AB - Sgk (serum- and glucocorticoid-induced protein kinase) is a serine/threonine-specific protein kinase that is transcriptionally regulated by serum, glucorticoids, and mineralocorticoids. Sgk regulates the amiloride-sensitive sodium channel in kidney principal cells. Insulin and insulin-like growth factor-1 stimulate activity of Sgk by a mechanism mediated by phosphoinositide-dependent kinases (PDK)-1 and -2. In this study, we demonstrate that incubation of transfected cells with 8-(4-chlorophenylthio)-cAMP (8CPT-cAMP; 0.2 mm) led to a 2-fold activation of recombinant Sgk expressed in COS7 cells. Furthermore, the combination of insulin plus 8CPT-cAMP elicited a larger response than either agent alone. The effect of insulin was inhibited by wortmannin (100 nm), but not by the cyclic AMP-dependent protein kinase (PKA) inhibitor, H89 (10 microm). As expected, the effect of 8CPT-cAMP was completely blocked by H89. Surprisingly, the effect of 8CPT-cAMP was also inhibited by wortmannin, suggesting that phosphorylation of Sgk by PDK-1 and/or -2 is required for activation by 8CPT-cAMP. Mutational analysis led to similar conclusions. The Thr(369) --> Ala mutant, lacking the PKA phosphorylation site, was activated by insulin but not 8CPT-cAMP. In contrast, the Ser(422) --> Ala mutant, lacking a PDK-2 phosphorylation site, was inactive and resistant to activation by either insulin or 8CPT-cAMP. In summary, Sgk is subject to complex regulatory mechanisms. In addition to regulation at the level of gene expression, the enzymatic activity of Sgk is regulated by multiple protein kinases, including PKA, PDK-1, and PDK-2. Cross-talk among these signaling pathways may play an important role in the pathogenesis of the hypertension associated with hyperinsulinemia, obesity, and insulin resistance. JF - The Journal of biological chemistry AU - Perrotti, N AU - He, R A AU - Phillips, S A AU - Haft, C R AU - Taylor, S I AD - Diabetes Branch, Division of Intramural Research, NIDDK, Bethesda, Maryland 20892, USA. Y1 - 2001/03/23/ PY - 2001 DA - 2001 Mar 23 SP - 9406 EP - 9412 VL - 276 IS - 12 SN - 0021-9258, 0021-9258 KW - Androstadienes KW - 0 KW - Enzyme Inhibitors KW - Glucocorticoids KW - Immediate-Early Proteins KW - Insulin KW - Isoquinolines KW - Nuclear Proteins KW - Recombinant Proteins KW - Sulfonamides KW - Cyclic AMP KW - E0399OZS9N KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - serum-glucocorticoid regulated kinase KW - N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide KW - M876330O56 KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - COS Cells KW - Androstadienes -- pharmacology KW - Recombinant Proteins -- genetics KW - Glucocorticoids -- pharmacology KW - Mutagenesis KW - Blood KW - Isoquinolines -- pharmacology KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Enzyme Induction KW - Enzyme Inhibitors -- pharmacology KW - Recombinant Proteins -- antagonists & inhibitors KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cyclic AMP -- pharmacology KW - Protein-Serine-Threonine Kinases -- genetics KW - Insulin -- pharmacology KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76983577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+serum-+and+glucocorticoid-induced+protein+kinase+%28Sgk%29+by+cyclic+AMP+and+insulin.&rft.au=Perrotti%2C+N%3BHe%2C+R+A%3BPhillips%2C+S+A%3BHaft%2C+C+R%3BTaylor%2C+S+I&rft.aulast=Perrotti&rft.aufirst=N&rft.date=2001-03-23&rft.volume=276&rft.issue=12&rft.spage=9406&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Escherichia coli MutS,L Modulate RuvAB-dependent Branch Migration between Diverged DNA AN - 17818802; 4857381 AB - This study examines the interaction between Escherichia coli MutS,L and E. coli RuvAB during E. coli RecA-promoted strand exchange. RuvAB is a branch migration complex that stimulates heterologous strand exchange. Previous studies indicate that RuvAB increases the rate at which heteroduplex products are formed by RecA, that RuvA and RuvB are required for this stimulation, and that RuvAB does not stimulate homologous strand exchange. This study indicates that MutS,L inhibit the formation of full-length heteroduplex DNA between M13-fd DNA in the presence of RuvAB, such that less than 2% of the linear substrate is converted to product. Inhibition depends on the time at which MutS,L are added to the reaction and is strongest when MutS,L are added during initiation. The kinetics of the strand exchange reaction suggest that MutS,L directly inhibit RuvAB-dependent branch migration in the absence of RecA. The inhibition requires the formation of base-base mismatches and ATP utilization; no effect on RuvAB-promoted strand exchange is seen if an ATP-deficient mutant of MutS (MutS501) is included in the reaction instead of wild-type MutS. These results are consistent with a role for MutS,L in maintaining genomic stability and replication fidelity. JF - Journal of Biological Chemistry AU - Fabisiewicz, A AU - Worth Jr, L AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, worth@niehs.nih.gov Y1 - 2001/03/23/ PY - 2001 DA - 2001 Mar 23 SP - 9413 EP - 9420 VL - 276 IS - 12 SN - 0021-9258, 0021-9258 KW - MutL protein KW - MutS protein KW - RuvA protein KW - RuvB protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA biosynthesis KW - DNA-binding protein KW - Escherichia coli KW - ATP KW - RecA protein KW - J 02725:DNA KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17818802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Escherichia+coli+MutS%2CL+Modulate+RuvAB-dependent+Branch+Migration+between+Diverged+DNA&rft.au=Fabisiewicz%2C+A%3BWorth+Jr%2C+L&rft.aulast=Fabisiewicz&rft.aufirst=A&rft.date=2001-03-23&rft.volume=276&rft.issue=12&rft.spage=9413&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA biosynthesis; RecA protein; ATP; DNA-binding protein ER - TY - CONF T1 - Post-exposure DNA vaccination protects mice against rabies virus AN - 17846433; 4874220 AB - Post-exposure anti-rabies vaccination for individuals who have not previously been immunized against rabies includes a cell culture-derived vaccine and a one time injection of rabies immune globulin. Recent studies have shown DNA vaccinations to be highly effective in rabies pre-exposure experiments, but post-exposure protection has not been achieved. This failure is likely due to the slow onset of DNA vaccine induced antibody production. In an attempt to accelerate the onset of the antibody response, we manipulated variables, such as the route of vaccination and booster frequency. Anti-rabies virus antibody was detected 5 days after the initial DNA vaccination. Using this vaccination protocol and a single non-protective dose of anti-rabies immune serum, we questioned whether mice injected 6 h previously with rabies virus would be protected if a DNA vaccine was substituted for the cell culture-derived human diploid cell vaccine (HDCV). The DNA vaccine protected 87% of the mice (P = 0.00005, compared with unvaccinated control mice). Some 75% of mice receiving HDCV were protected (P = 0.00097, compared with unvaccinated control mice). Mice receiving only anti-rabies immune serum were not protected (P > 0.05 compared to unvaccinated control mice). Thus, post-exposure therapy, substituting a DNA vaccine for HDCV, did not compromise protection against rabies virus. JF - Vaccine AU - Lodmell, D L AU - Ewalt, L C Y1 - 2001/03/21/ PY - 2001 DA - 2001 Mar 21 SP - 2468 EP - 2473 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 19 IS - 17-19 KW - man KW - mice KW - post-exposure KW - rabies virus KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Antibody response KW - DNA vaccines KW - Rabies KW - Rabies virus KW - Vaccines KW - Immunoglobulins KW - F 06807:Active immunization KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17846433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Post-exposure+DNA+vaccination+protects+mice+against+rabies+virus&rft.au=Lodmell%2C+D+L%3BEwalt%2C+L+C&rft.aulast=Lodmell&rft.aufirst=D&rft.date=2001-03-21&rft.volume=19&rft.issue=17-19&rft.spage=2468&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Acute alcohol intoxication and endotoxemia desensitize HIV-1 gp120-induced CC-chemokine production by Kupffer cells. AN - 70885457; 11388697 AB - Chemokines are involved in the inhibition of HIV-1 infection and in the pathogenesis of tissue injury in a number of conditions, including endotoxemia and alcoholic liver disease. CC chemotactic peptides (MIP-1alpha, MCP-1 and RANTES) are produced by a wide variety of cell types in response to immunological stimuli, bacterial endotoxin and gp120 from HIV-1 and HIV-2. This work tests the hypothesis that prior exposure to endotoxin and/or ethanol in vivo inhibits the production of CC-chemokines following a secondary challenge with HIV-1 gp120 in vitro. Male Sprague-Dawley rats received in intravenous infusion of ethanol to maintain blood ethanol level at 170 mg/dl for 3 hr. Escherichia coli LPS (1 mg/Kg) was given intravenously 5 min after the ethanol bolus was injected. Control groups received similar volumes of saline. Three hr after LPS treatment, Kupffer cells were obtained and treated with HIV-1 gp120 (5 microg/10(6) cells/24 hr). At the end of the incubation period, cells were obtained for RT-PCR analysis of CC-chemokine mRNA expression. Chemokine release in culture supernatants was measured by ELISA. Results show that in vivo ethanol was associated with downregulation of MIP-1alpha and MCP-1 mRNA expression and protein release in primary cultures of Kupffer cells. However, ethanol alone primed isolated Kupffer cells for enhanced RANTES mRNA and protein release in the presence or absence of HIV-1 gp120. These results demonstrate that acute ethanol intoxication and endotoxemia may selectively act as a desensitizing agent in response to a secondary challenge with bacterial or viral products. JF - Life sciences AU - Bautista, A P AD - Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans 70112, USA. abauti@lsuhsc.edu Y1 - 2001/03/16/ PY - 2001 DA - 2001 Mar 16 SP - 1939 EP - 1949 VL - 68 IS - 17 SN - 0024-3205, 0024-3205 KW - Chemokine CCL3 KW - 0 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Chemokines, CC KW - HIV Envelope Protein gp120 KW - Lipopolysaccharides KW - Macrophage Inflammatory Proteins KW - RNA, Messenger KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Chemokine CCL5 -- biosynthesis KW - Animals KW - Macrophage Inflammatory Proteins -- genetics KW - RNA, Messenger -- biosynthesis KW - Chemokine CCL5 -- genetics KW - Chemokine CCL5 -- secretion KW - Rats KW - Rats, Sprague-Dawley KW - Ethanol -- toxicity KW - Lipopolysaccharides -- toxicity KW - RNA, Messenger -- secretion KW - Down-Regulation -- drug effects KW - Macrophage Inflammatory Proteins -- biosynthesis KW - Macrophage Inflammatory Proteins -- secretion KW - Male KW - HIV Envelope Protein gp120 -- pharmacology KW - Endotoxemia -- genetics KW - Kupffer Cells -- secretion KW - Kupffer Cells -- metabolism KW - Kupffer Cells -- drug effects KW - Chemokines, CC -- secretion KW - Alcoholic Intoxication -- genetics KW - Chemokines, CC -- genetics KW - Chemokines, CC -- biosynthesis KW - Alcoholic Intoxication -- metabolism KW - Endotoxemia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70885457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Acute+alcohol+intoxication+and+endotoxemia+desensitize+HIV-1+gp120-induced+CC-chemokine+production+by+Kupffer+cells.&rft.au=Bautista%2C+A+P&rft.aulast=Bautista&rft.aufirst=A&rft.date=2001-03-16&rft.volume=68&rft.issue=17&rft.spage=1939&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ewing's sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5. AN - 77029831; 11289151 AB - In this study, we investigated the sensitivity of Ewing's sarcoma family tumors (ESFTs) of children and adolescents to the tumor necrosis factor-related apoptosis-inducing Ligand (TRAIL). TRAIL binds to death receptors (DRs) DR4, DR5, DcR1, and DcR2. Either DR4 or DR5 can induce apoptosis, whereas DcR1 and DcR2 are considered inhibitory receptors. Nine of 10 ESFT cell lines, including several that were Fas resistant, underwent apoptosis with TRAIL through activation of caspase-10, capase-8 (FLICE), caspase-3, and caspase-9. In contrast to the Fas signaling pathway, caspase-10, but not caspase-8 or the Fas-associated death domain-containing molecule, was recruited to the TRAIL receptor-associated signaling complex. We found that 9 of 10 ESFT cell lines expressed both DR4 and DR5 by Western blotting, whereas the TRAIL-resistant line expressed only DR4. However, DR4 was absent from the cell surface in the resistant and two additional lines (three of five tested lines), suggesting that it may have been nonfunctional. On the contrary, DR5 was located on the cell surface in all four sensitive lines tested, being absent only from the cell surface of the resistant line that was also DR5-negative by Western blotting. In agreement with these findings, the resistance of the line was overcome by restoration of DR5 levels by transfection. Levels of DcR1 and DcR2 or levels of the FLICE-inhibitory protein (FLIP) did not correlate with TRAIL resistance, and protein synthesis inhibition did not sensitize the TRAIL-resistant line to TRAIL. Because these data suggested that sensitivity of ESFTs to TRAIL was mainly based on the presence of DR4/DR5, we investigated the presence of these receptors in 32 ESFT tissue sections by immunohistochemistry. We found that 23 of 32 tumor tissues (72%) expressed both receptors, 8 of 32 (25%) expressed one receptor only, and 1 was negative for both. Our finding of wide expression of DR4/DR5 in ESFT in vivo, in combination with their high sensitivity to TRAIL in vitro and the reported lack of toxicity of TRAIL in mice and monkeys, suggests that TRAIL may be a novel effective agent in the treatment of ESFTs. JF - Cancer research AU - Mitsiades, N AU - Poulaki, V AU - Mitsiades, C AU - Tsokos, M AD - National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 2704 EP - 2712 VL - 61 IS - 6 SN - 0008-5472, 0008-5472 KW - Apoptosis Regulatory Proteins KW - 0 KW - CASP8 and FADD-Like Apoptosis Regulating Protein KW - CFLAR protein, human KW - Carrier Proteins KW - Intracellular Signaling Peptides and Proteins KW - Isoenzymes KW - Membrane Glycoproteins KW - Protein Synthesis Inhibitors KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - Receptors, Tumor Necrosis Factor KW - Recombinant Proteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFRSF10A protein, human KW - TNFRSF10B protein, human KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Cycloheximide KW - 98600C0908 KW - Caspases KW - EC 3.4.22.- KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Enzyme Activation KW - Humans KW - Carrier Proteins -- biosynthesis KW - Caspases -- metabolism KW - Isoenzymes -- metabolism KW - Tumor Cells, Cultured KW - Protein Synthesis Inhibitors -- pharmacology KW - Transfection KW - Cycloheximide -- pharmacology KW - Apoptosis -- drug effects KW - Cell Membrane -- metabolism KW - Sarcoma, Ewing -- pathology KW - Receptors, Tumor Necrosis Factor -- biosynthesis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Sarcoma, Ewing -- metabolism KW - Membrane Glycoproteins -- pharmacology KW - Sarcoma, Ewing -- drug therapy KW - Receptors, Tumor Necrosis Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77029831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Ewing%27s+sarcoma+family+tumors+are+sensitive+to+tumor+necrosis+factor-related+apoptosis-inducing+ligand+and+express+death+receptor+4+and+death+receptor+5.&rft.au=Mitsiades%2C+N%3BPoulaki%2C+V%3BMitsiades%2C+C%3BTsokos%2C+M&rft.aulast=Mitsiades&rft.aufirst=N&rft.date=2001-03-15&rft.volume=61&rft.issue=6&rft.spage=2704&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cis-polyunsaturated fatty acids stimulate beta1 integrin-mediated adhesion of human breast carcinoma cells to type IV collagen by activating protein kinases C-epsilon and -mu. AN - 77025583; 11289113 AB - We have investigated the effects of various fatty acids (FAs) on integrin-mediated MDA-MB-435 breast carcinoma cell adhesion to type IV collagen (collagen IV) in vitro. Arachidonic acid (AA) and linoleic acid both induced a dose-dependent increase in cell adhesion to collagen IV with no significant increase in nonspecific adhesion to polylysine and BSA. Oleic acid (a monounsaturated FA), AA methyl ester, and linoelaidic acid (a trans-isomer of linoleic acid) failed to stimulate adhesion to collagen IV, suggesting that these effects required cis-polyunsaturation and a free carboxylic moiety and that they were not due to membrane perturbations. Calphostin C, a protein kinase C (PKC) inhibitor, blocked cis-polyunsaturated FA (cis-PUFA)-induced cell adhesion in a dose-dependent manner, suggesting a role for a calcium-dependent PKC in this signal transduction pathway. Immunoblotting revealed that cis-PUFAs induced the translocation of PKCepsilon and PKCmu, two of the novel PKC isozymes, from the cytosol to the membrane. In contrast, a conventional PKC isozyme, PKCalpha, as well as the atypical isozymes, PKCzeta and PKCiota, did not translocate after cis-PUFA treatment. Function-blocking antibodies specific for alpha1, alpha2, and beta1, integrin subunits inhibited cell adhesion to collagen IV, whereas antibodies to alpha3 and alpha5 did not. No increase in the expression of these integrins on the cell surface was detected after the incubation of cells with cis-PUFAs, suggesting that there is an increase in the activity, but not in the amount, of these beta1, integrins. Altogether, these data suggest that cis-PUFAs enhance human breast cancer cell adhesion to collagen IV by selectively activating specific PKC isozymes, which leads to the activation of beta1 integrins. JF - Cancer research AU - Palmantier, R AU - George, M D AU - Akiyama, S K AU - Wolber, F M AU - Olden, K AU - Roberts, J D AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 2445 EP - 2452 VL - 61 IS - 6 SN - 0008-5472, 0008-5472 KW - Antigens, CD29 KW - 0 KW - Dietary Fats, Unsaturated KW - Fatty Acids, Unsaturated KW - Isoenzymes KW - Arachidonic Acid KW - 27YG812J1I KW - Oleic Acid KW - 2UMI9U37CP KW - Collagen KW - 9007-34-5 KW - Linoleic Acid KW - 9KJL21T0QJ KW - protein kinase D KW - EC 2.7.10.- KW - PRKCE protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-epsilon KW - Index Medicus KW - Immunoblotting KW - Cell Adhesion -- physiology KW - Arachidonic Acid -- pharmacology KW - Humans KW - Adenocarcinoma -- pathology KW - Stimulation, Chemical KW - Adenocarcinoma -- enzymology KW - Dietary Fats, Unsaturated -- pharmacology KW - Tumor Cells, Cultured KW - Enzyme Activation -- drug effects KW - Flow Cytometry KW - Linoleic Acid -- pharmacology KW - Oleic Acid -- pharmacology KW - Substrate Specificity KW - Cell Adhesion -- drug effects KW - Protein Kinase C -- metabolism KW - Antigens, CD29 -- biosynthesis KW - Breast Neoplasms -- pathology KW - Antigens, CD29 -- physiology KW - Collagen -- metabolism KW - Fatty Acids, Unsaturated -- pharmacology KW - Breast Neoplasms -- enzymology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77025583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Cis-polyunsaturated+fatty+acids+stimulate+beta1+integrin-mediated+adhesion+of+human+breast+carcinoma+cells+to+type+IV+collagen+by+activating+protein+kinases+C-epsilon+and+-mu.&rft.au=Palmantier%2C+R%3BGeorge%2C+M+D%3BAkiyama%2C+S+K%3BWolber%2C+F+M%3BOlden%2C+K%3BRoberts%2C+J+D&rft.aulast=Palmantier&rft.aufirst=R&rft.date=2001-03-15&rft.volume=61&rft.issue=6&rft.spage=2445&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dimethylbenzanthracene carcinogenesis in Gadd45a-null mice is associated with decreased DNA repair and increased mutation frequency. AN - 77023870; 11289119 AB - Mice lacking the Gadd45a gene are susceptible to ionizing radiation-induced tumors. Increased levels of Gadd45a transcript and protein are seen after treatment of cells with ionizing radiation as well as many other agents and treatments that damage DNA. Because cells deficient in Gadd45a were shown to have a partial defect in the global genomic repair component of the nucleotide excision repair pathway of UV-induced photoproducts, dimethylbenzanthracene (DMBA) carcinogenesis was investigated because this agent produces bulky adducts in DNA that are also repaired by nucleotide excision repair. Wild-type mice and mice deficient for Gadd45a were injected with a single i.p. dose of DMBA at 10-14 days of age. The latency for spontaneous deaths was slightly decreased for Gadd45a-null mice compared with wild-type mice. At 17 months, all surviving animals were killed, and similar percentages of each genotype were found to have tumors. However, nearly twice as many Gadd45a-null than wild-type mice had multiple tumors, and three times as many had multiple malignant tumors. The predominant tumor types in wild-type mice were lymphoma and tumors of the intestines and liver. In Gadd45a-null mice, there was a dramatic increase in female ovarian tumors, male hepatocellular tumors, and in vascular tumors in both sexes. In wild-type mice, this dose of DMBA induced a >5-fold increase in Gadd45a transcript in the spleen and ovary, whereas the increase in liver was >20-fold. Nucleotide excision repair, which repairs both UV- and DMBA-induced DNA lesions, was substantially reduced in Gadd45a-null lymphoblasts. Mutation frequency after DMBA treatment was threefold higher in Gadd45a-null liver compared with wild-type liver. Therefore, lack of basal and DMBA-induced Gadd45a may result in enhanced tumorigenesis because of decreased DNA repair and increased mutation frequency. Genomic instability, decreased cell cycle checkpoints, and partial loss of normal growth control in cells from Gadd45a-null mice may also contribute to this process. JF - Cancer research AU - Hollander, M C AU - Kovalsky, O AU - Salvador, J M AU - Kim, K E AU - Patterson, A D AU - Haines, D C AU - Fornace, A J AD - NIH, National Cancer Institute (NCI), Division of Basic Science, Bethesda, Maryland 20892, USA. ch96b@nih.gov Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 2487 EP - 2491 VL - 61 IS - 6 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Liver Neoplasms, Experimental -- genetics KW - Animals KW - Ovarian Neoplasms -- genetics KW - Vascular Neoplasms -- genetics KW - Ovarian Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Vascular Neoplasms -- chemically induced KW - Mice KW - Male KW - Female KW - Gene Deletion KW - DNA Repair -- genetics KW - Neoplasms, Experimental -- chemically induced KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Proteins -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77023870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Dimethylbenzanthracene+carcinogenesis+in+Gadd45a-null+mice+is+associated+with+decreased+DNA+repair+and+increased+mutation+frequency.&rft.au=Hollander%2C+M+C%3BKovalsky%2C+O%3BSalvador%2C+J+M%3BKim%2C+K+E%3BPatterson%2C+A+D%3BHaines%2C+D+C%3BFornace%2C+A+J&rft.aulast=Hollander&rft.aufirst=M&rft.date=2001-03-15&rft.volume=61&rft.issue=6&rft.spage=2487&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus. AN - 76987644; 11257238 AB - Abnormalities in the glutamatergic system, glutamate/dopamine/gamma-aminobutyric acid interactions, and cortical development are implicated in schizophrenia. Moreover, patients with schizophrenia show symptom exacerbation in response to N-methyl-D-aspartate (NMDA) antagonist drugs. Using an animal model of schizophrenia, we compared the impact of neonatal and adult hippocampal lesions on behavioral responses to MK-801, a noncompetitive NMDA antagonist. Neonatal rats were lesioned on postnatal day 7. Their motor activity in response to MK-801 was tested at a juvenile age, in adolescence, and in adulthood. We also measured binding of [(3)H]MK-801 and the expression of NR1 messenger RNA (mRNA) in the medial prefrontal cortex and nucleus accumbens. Adult rats received similar lesions and were tested 4 and 8 weeks after the lesion. As juveniles, neonatally lesioned rats did not differ from control rats in responsiveness to MK-801, whereas in adolescence and adulthood they showed more pronounced hyperactivity than control rats. The adult lesion did not alter behaviors elicited by MK-801. Neonatally lesioned rats showed no apparent changes in [(3)H]MK-801 binding or expression of the NR1 mRNA. These results suggest that an early lesion of the ventral hippocampus affects development of neural systems involved in MK-801 action without changes at the NMDA receptor level, and they show that the behavioral changes manifest first in early adulthood. JF - Biological psychiatry AU - Al-Amin, H A AU - Shannon Weickert, C AU - Weinberger, D R AU - Lipska, B K AD - Clinical Brain Disorders Branch, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 528 EP - 539 VL - 49 IS - 6 SN - 0006-3223, 0006-3223 KW - Excitatory Amino Acid Antagonists KW - 0 KW - NR1 NMDA receptor KW - RNA, Messenger KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - In Situ Hybridization KW - Age Factors KW - Prefrontal Cortex -- metabolism KW - Random Allocation KW - RNA, Messenger -- drug effects KW - Binding, Competitive -- physiology KW - Nucleus Accumbens -- metabolism KW - Dopamine -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Female KW - Dizocilpine Maleate -- adverse effects KW - Behavior, Animal -- drug effects KW - Hyperkinesis -- chemically induced KW - Excitatory Amino Acid Antagonists -- adverse effects KW - Dizocilpine Maleate -- pharmacokinetics KW - Disease Models, Animal KW - Excitatory Amino Acid Antagonists -- pharmacokinetics KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76987644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Delayed+onset+of+enhanced+MK-801-induced+motor+hyperactivity+after+neonatal+lesions+of+the+rat+ventral+hippocampus.&rft.au=Al-Amin%2C+H+A%3BShannon+Weickert%2C+C%3BWeinberger%2C+D+R%3BLipska%2C+B+K&rft.aulast=Al-Amin&rft.aufirst=H&rft.date=2001-03-15&rft.volume=49&rft.issue=6&rft.spage=528&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trial designs for the early clinical development of therapeutic cancer vaccines. AN - 76970787; 11251017 AB - There are major differences between therapeutic tumor vaccines and chemotherapeutic agents that have important implications for the design of early clinical trials. Many vaccines are inherently safe and do not require phase I dose finding trials. Patients with advanced cancers and compromised immune systems are not good candidates for assessing either the toxicity or efficacy of therapeutic cancer vaccines. The rapid pace of development of new vaccine candidates and the variety of possible adjuvants and modifications in method of administration makes it important to use efficient designs for clinical screening and evaluation of vaccine regimens. We review the potential advantages of a wide range of clinical trial designs for the development of tumor vaccines. We address the role of immunological endpoints in early clinical trials of tumor vaccines, investigate the design implications of attempting to use disease stabilization as an end point and discuss the difficulties of reliably utilizing historical control data. Several conclusions for expediting the clinical development of effective cancer vaccines are proposed. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Simon, R M AU - Steinberg, S M AU - Hamilton, M AU - Hildesheim, A AU - Khleif, S AU - Kwak, L W AU - Mackall, C L AU - Schlom, J AU - Topalian, S L AU - Berzofsky, J A AD - Branch of Biometric Research, Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7434, USA. rsimon@nib.gov Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 1848 EP - 1854 VL - 19 IS - 6 SN - 0732-183X, 0732-183X KW - Adjuvants, Immunologic KW - 0 KW - Antineoplastic Agents KW - Cancer Vaccines KW - Index Medicus KW - Humans KW - Cohort Studies KW - Treatment Outcome KW - Immunocompromised Host KW - Research Design KW - Adjuvants, Immunologic -- therapeutic use KW - Neoplasms -- drug therapy KW - Randomized Controlled Trials as Topic KW - Neoplasms -- virology KW - Endpoint Determination KW - Cancer Vaccines -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76970787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Clinical+trial+designs+for+the+early+clinical+development+of+therapeutic+cancer+vaccines.&rft.au=Simon%2C+R+M%3BSteinberg%2C+S+M%3BHamilton%2C+M%3BHildesheim%2C+A%3BKhleif%2C+S%3BKwak%2C+L+W%3BMackall%2C+C+L%3BSchlom%2C+J%3BTopalian%2C+S+L%3BBerzofsky%2C+J+A&rft.aulast=Simon&rft.aufirst=R&rft.date=2001-03-15&rft.volume=19&rft.issue=6&rft.spage=1848&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defining the minimal length of sequence homology required for selective gene isolation by TAR cloning. AN - 76957926; 11239009 AB - The transformation-associated recombination (TAR) cloning technique allows selective and accurate isolation of chromosomal regions and genes from complex genomes. The technique is based on in vivo recombination between genomic DNA and a linearized vector containing homologous sequences, or hooks, to the gene of interest. The recombination occurs during transformation of yeast spheroplasts that results in the generation of a yeast artificial chromosome (YAC) containing the gene of interest. To further enhance and refine the TAR cloning technology, we determined the minimal size of a specific hook required for gene isolation utilizing the Tg.AC mouse transgene as a targeted region. For this purpose a set of vectors containing a B1 repeat hook and a Tg.AC-specific hook of variable sizes (from 20 to 800 bp) was constructed and checked for efficiency of transgene isolation by a radial TAR cloning. When vectors with a specific hook that was >/=60 bp were utilized, approximately 2% of transformants contained circular YACs with the Tg.AC transgene sequences. Efficiency of cloning dramatically decreased when the TAR vector contained a hook of 40 bp or less. Thus, the minimal length of a unique sequence required for gene isolation by TAR is approximately 60 bp. No transgene-positive YAC clones were detected when an ARS element was incorporated into a vector, demonstrating that the absence of a yeast origin of replication in a vector is a prerequisite for efficient gene isolation by TAR cloning. JF - Nucleic acids research AU - Noskov, V N AU - Koriabine, M AU - Solomon, G AU - Randolph, M AU - Barrett, J C AU - Leem, S H AU - Stubbs, L AU - Kouprina, N AU - Larionov, V AD - Laboratory of Molecular Genetics and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 1 VL - 29 IS - 6 KW - Recombinant Fusion Proteins KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Animals KW - Genes, ras -- genetics KW - Mice KW - Transgenes -- genetics KW - Replication Origin -- genetics KW - Genetic Vectors -- genetics KW - DNA -- genetics KW - Recombinant Fusion Proteins -- isolation & purification KW - Recombinant Fusion Proteins -- genetics KW - Cloning, Molecular -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76957926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Defining+the+minimal+length+of+sequence+homology+required+for+selective+gene+isolation+by+TAR+cloning.&rft.au=Noskov%2C+V+N%3BKoriabine%2C+M%3BSolomon%2C+G%3BRandolph%2C+M%3BBarrett%2C+J+C%3BLeem%2C+S+H%3BStubbs%2C+L%3BKouprina%2C+N%3BLarionov%2C+V&rft.aulast=Noskov&rft.aufirst=V&rft.date=2001-03-15&rft.volume=29&rft.issue=6&rft.spage=E32&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genomics. 1999 Dec 1;62(2):285-8 [10610723] Mol Carcinog. 1998 Apr;21(4):244-50 [9585254] Genomics. 2000 Dec 15;70(3):292-9 [11161779] Proc Natl Acad Sci U S A. 1980 Aug;77(8):4559-63 [6449009] Genetics. 1989 May;122(1):19-27 [2659436] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Mol Cell Biol. 1993 Jul;13(7):3937-50 [8321201] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6186-90 [8016135] Gene. 1995 May 26;158(1):113-7 [7789793] Nucleic Acids Res. 1995 Jul 25;23(14):2799-800 [7651842] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):491-6 [8552668] Nucleic Acids Res. 1997 Jan 15;25(2):451-2 [9016579] Plasmid. 1997;38(2):91-6 [9339466] Mamm Genome. 1998 Feb;9(2):157-9 [9457679] Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4469-74 [9539761] Mutat Res. 2000 Jun 30;451(1-2):71-89 [10915866] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delta opioid peptide [D-Ala2, D-Leu5]enkephalin causes a near complete blockade of the neuronal damage caused by a single high dose of methamphetamine: examining the role of p53. AN - 70632231; 11169780 AB - The delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) has been reported to block the neurotoxicity induced by multiple administrations of a moderate dose of methamphetamine (METH). We examined in this study if DADLE might block the neurotoxicity caused by a single high dose of METH in CD-1 mice. The levels of dopamine transporter (DAT), tyrosine hydroxylase (TH), major biogenic amines including DA, 5-hydroxytryptamine (5-HT), and their metabolites were examined. In addition, since the tumor suppressor p53 has been implicated in the neurotoxicity of METH, this study also examined the levels of p53 mRNA and protein affected by METH and DADLE. METH (25 mg/kg, i.p.) caused significant losses of DAT, TH, DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-HT in the striatum within 72 h. The administration of a single dose of DADLE (20 mg/kg, i.p., 30 min before METH) caused a complete blockade of all losses induced by METH except for that of the DA content (a approximately 50% blockade). DADLE did not affect the changes of rectal temperature induced by the administration of the high dose of METH. METH increased p53 mRNA in the striatum and the hippocampus of CD-1 mouse. DADLE abolished the p53 mRNA increase caused by METH. METH tended to increase the p53 protein level at earlier time points. However, METH significantly decreased the p53 protein level by about 30% at the 72-h time point. DADLE blocked both the increase of p53 mRNA and the decrease of p53 protein caused by METH. These results demonstrate a neuroprotective effect of DADLE against the neuronal damage and the alteration of p53 gene expression caused by a single high dose of METH. The results also indicate an apparent discordance between the protein level of p53 and the neurotoxicity caused by a high dose of METH. Synapse 39:305-312, 2001. Published 2001 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Hayashi, T AU - Hirata, H AU - Asanuma, M AU - Ladenheim, B AU - Tsao, L I AU - Cadet, J L AU - Su, T P AD - Molecular Neuropsychiatry Section, Intramural Research Program, National Institute on Drug Abuse/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 305 EP - 312 VL - 39 IS - 4 SN - 0887-4476, 0887-4476 KW - Carrier Proteins KW - 0 KW - Central Nervous System Stimulants KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Neuroprotective Agents KW - Slc6a3 protein, mouse KW - Tumor Suppressor Protein p53 KW - Serotonin KW - 333DO1RDJY KW - Methamphetamine KW - 44RAL3456C KW - Enkephalin, Leucine-2-Alanine KW - 63631-40-3 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Transcription, Genetic -- drug effects KW - Carrier Proteins -- metabolism KW - Kinetics KW - Brain -- drug effects KW - Dopamine -- metabolism KW - Mice KW - Brain -- metabolism KW - Serotonin -- metabolism KW - Male KW - Tumor Suppressor Protein p53 -- physiology KW - Methamphetamine -- administration & dosage KW - Central Nervous System Stimulants -- administration & dosage KW - Tumor Suppressor Protein p53 -- metabolism KW - Methamphetamine -- toxicity KW - Nerve Degeneration -- drug therapy KW - Central Nervous System Stimulants -- toxicity KW - Nerve Degeneration -- metabolism KW - Enkephalin, Leucine-2-Alanine -- therapeutic use KW - Neuroprotective Agents -- therapeutic use KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Delta+opioid+peptide+%5BD-Ala2%2C+D-Leu5%5Denkephalin+causes+a+near+complete+blockade+of+the+neuronal+damage+caused+by+a+single+high+dose+of+methamphetamine%3A+examining+the+role+of+p53.&rft.au=Hayashi%2C+T%3BHirata%2C+H%3BAsanuma%2C+M%3BLadenheim%2C+B%3BTsao%2C+L+I%3BCadet%2C+J+L%3BSu%2C+T+P&rft.aulast=Hayashi&rft.aufirst=T&rft.date=2001-03-15&rft.volume=39&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of 13 super(32)P-DNA Postlabeling Studies on Occupational Cohorts Exposed to Air Pollution AN - 18474418; 5441481 AB - Industrial and urban workers may be exposed to significant levels of air pollutants resulting from the incomplete combustion of organic matter. The authors performed a meta-analysis of 13 DNA-adduct studies ( super(32)P-DNA postlabeling technique) on occupational cohorts exposed to air pollution. The association between levels of DNA adducts and air pollution exposure was significant both in heavily exposed industrial workers and in less severely exposed urban workers. Moreover, in an analysis using the seven studies that reported measuring levels of benzo[a] pyrene (B(a)P), a typical marker of exposure, DNA adduct levels in exposed workers (versus those in referents) were significantly correlated with air levels of B(a)P. The relation between DNA adducts and B(a)P was found to be linear at low doses and sublinear at high doses, indicating that DNA adduct formation tends to reach some kind of saturation point at higher levels of exposure to the chemical mixtures present in fumes. When the authors examined the efficiency of DNA adduct production associated with increasing air pollution exposures, the production of DNA adducts per unit of exposure was significantly decreased at higher B(a)P exposure levels. These findings suggest that linear downward extrapolations based on DNA adduct levels associated with B(a)P concentrations of greater than or equal to 20 ng/m super(3) might be affected by underestimation bias. JF - American Journal of Epidemiology AU - Peluso, M AU - Ceppi, M AU - Munnia, A AU - Puntoni, R AU - Parodi, S AD - Unit of Experimental Oncology, National Cancer Institute, Genoa, Italy Y1 - 2001/03/15/ PY - 2001 DA - 2001 Mar 15 SP - 546 EP - 558 VL - 153 IS - 6 SN - 0002-9262, 0002-9262 KW - man KW - Toxicology Abstracts KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18474418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Analysis+of+13+super%2832%29P-DNA+Postlabeling+Studies+on+Occupational+Cohorts+Exposed+to+Air+Pollution&rft.au=Peluso%2C+M%3BCeppi%2C+M%3BMunnia%2C+A%3BPuntoni%2C+R%3BParodi%2C+S&rft.aulast=Peluso&rft.aufirst=M&rft.date=2001-03-15&rft.volume=153&rft.issue=6&rft.spage=546&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. AN - 76972772; 11248066 AB - Cryptococcus neoformans STE12alpha, a homologue of Saccharomyces cerevisiae STE12, exists only in MATalpha strains. We identified another STE12 homologue, STE12a, which is MATa specific. As in the case with Deltaste12alpha, the mating efficiency for Deltaste12a was reduced significantly. The Deltaste12a strains surprisingly still mated with Deltaste12alpha strains. In MATalpha strains, STE12a functionally complemented STE12alpha for mating efficacy, haploid fruiting, and regulation of capsule size in the mouse brain. Furthermore, when STE12a was replaced with two copies of STE12alpha, the resulting MATa strain produced hyphae on filament agar. STE12a regulates mRNA levels of several genes that are important for virulence including CNLAC1 and CAP genes. STE12a also modulates enzyme activities of phospholipase and superoxide dismutase. Importantly, deletion of STE12a markedly reduced the virulence in mice, as is the case with STE12alpha. Brain smears of mice infected with the Deltaste12a strain showed yeast cells with a considerable reduction in capsule size compared with those infected with STE12a strains. When the disrupted locus of ste12a was replaced with a wild-type STE12a gene, both in vivo and in vitro mutant phenotypes were reversed. These results suggest that STE12a and STE12alpha have similar functions, and that the mating type of the cells influences the alleles to exert their biological effects. C. neoformans, thus, is the first fungal species that contains a mating-type-specific STE12 homologue in each mating type. Our results demonstrate that mating-type-specific genes are not only important for saprobic reproduction but also play an important role for survival of the organism in host tissue. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chang, Y C AU - Penoyer, L A AU - Kwon-Chung, K J AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/03/13/ PY - 2001 DA - 2001 Mar 13 SP - 3258 EP - 3263 VL - 98 IS - 6 SN - 0027-8424, 0027-8424 KW - DNA, Fungal KW - 0 KW - Fungal Proteins KW - Homeodomain Proteins KW - MATA1 protein, S cerevisiae KW - Repressor Proteins KW - STE12 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Index Medicus KW - Virulence KW - Phenotype KW - Base Sequence KW - Genes, Fungal KW - Molecular Sequence Data KW - Mutagenesis KW - Genes, Mating Type, Fungal KW - Cloning, Molecular KW - Transcription Factors -- physiology KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Fungal Proteins -- physiology KW - Repressor Proteins -- metabolism KW - Homeodomain Proteins -- metabolism KW - Cryptococcus neoformans -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76972772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+second+STE12+homologue+of+Cryptococcus+neoformans+is+MATa-specific+and+plays+an+important+role+in+virulence.&rft.au=Chang%2C+Y+C%3BPenoyer%2C+L+A%3BKwon-Chung%2C+K+J&rft.aulast=Chang&rft.aufirst=Y&rft.date=2001-03-13&rft.volume=98&rft.issue=6&rft.spage=3258&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-03-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF242352; GENBANK N1 - SuppNotes - Cited By: Genetics. 1999 Dec;153(4):1601-15 [10581270] Infect Immun. 1996 Jun;64(6):1977-83 [8675296] Clin Microbiol Rev. 2000 Jan;13(1):122-43, table of contents [10627494] Med Mycol. 1999 Dec;37(6):375-89 [10647118] J Exp Med. 2000 Mar 6;191(5):871-82 [10704467] Mol Microbiol. 2000 Apr;36(2):290-301 [10792717] J Bacteriol. 2000 Nov;182(21):6222-7 [11029445] J Clin Invest. 1974 Oct;54(4):1005-9 [4430711] Mycologia. 1975 Nov-Dec;67(6):1197-200 [765816] Mycologia. 1976 Jul-Aug;68(4):943-6 [790173] Am J Epidemiol. 1978 Oct;108(4):337-40 [364979] Antonie Van Leeuwenhoek. 1982;48(1):25-38 [7046630] Genes Dev. 1991 Apr;5(4):594-604 [1672661] Infect Immun. 1992 Feb;60(2):602-5 [1730495] Cell. 1992 Mar 20;68(6):1077-90 [1547504] EMBO J. 1992 Dec;11(13):4993-5003 [1361172] Genes Dev. 1994 Jan;8(2):245-57 [7905452] Mol Cell Biol. 1994 Jul;14(7):4912-9 [8007987] J Biol Chem. 1994 Sep 16;269(37):22945-51 [8083193] Genes Dev. 1994 Dec 15;8(24):2974-85 [8001818] Cell. 1995 Jan 27;80(2):187-97 [7834739] Eur J Biochem. 1995 Oct 1;233(1):73-82 [7588776] Microbiology. 1996 Jun;142 ( Pt 6):1557-65 [8704997] Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7327-31 [8692992] J Exp Med. 1996 Aug 1;184(2):377-86 [8760791] J Infect Dis. 1997 Feb;175(2):414-20 [9203663] Mol Microbiol. 1997 Dec;26(5):951-60 [9426132] Microbiol Mol Biol Rev. 1998 Mar;62(1):55-70 [9529887] Infect Immun. 1998 May;66(5):2230-6 [9573112] J Biol Chem. 1998 Jul 24;273(30):19153-9 [9668101] Mol Cell Endocrinol. 1998 Apr 30;139(1-2):25-35 [9705071] Trends Cell Biol. 1998 Sep;8(9):348-53 [9728395] Development. 1999 May;126(10):2253-60 [10207149] J Bacteriol. 1999 Sep;181(18):5636-43 [10482503] Mol Cell Biol. 2000 Jan;20(1):352-62 [10594037] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice transgenically overexpressing sulfonylurea receptor 1 in forebrain resist seizure induction and excitotoxic neuron death. AN - 76972112; 11248115 AB - The ability of the sulfonylurea receptor (SUR) 1 to suppress seizures and excitotoxic neuron damage was assessed in mice transgenically overexpressing this receptor. Fertilized eggs from FVB mice were injected with a construct containing SUR cDNA and a calcium-calmodulin kinase IIalpha promoter. The resulting mice showed normal gross anatomy, brain morphology and histology, and locomotor and cognitive behavior. However, they overexpressed the SUR1 transgene, yielding a 9- to 12-fold increase in the density of [(3)H]glibenclamide binding to the cortex, hippocampus, and striatum. These mice resisted kainic acid-induced seizures, showing a 36% decrease in average maximum seizure intensity and a 75% survival rate at a dose that killed 53% of the wild-type mice. Kainic acid-treated transgenic mice showed no significant loss of hippocampal pyramidal neurons or expression of heat shock protein 70, whereas wild-type mice lost 68-79% of pyramidal neurons in the CA1-3 subfields and expressed high levels of heat shock protein 70 after kainate administration. These results indicate that the transgenic overexpression of SUR1 alone in forebrain structures significantly protects mice from seizures and neuronal damage without interfering with locomotor or cognitive function. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hernández-Sánchez, C AU - Basile, A S AU - Fedorova, I AU - Arima, H AU - Stannard, B AU - Fernandez, A M AU - Ito, Y AU - LeRoith, D AD - Section on Molecular and Cellular Physiology, Clinical Endocrinology Branch, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/03/13/ PY - 2001 DA - 2001 Mar 13 SP - 3549 EP - 3554 VL - 98 IS - 6 SN - 0027-8424, 0027-8424 KW - Abcc8 protein, mouse KW - 0 KW - Excitatory Amino Acid Agonists KW - Potassium Channels KW - Potassium Channels, Inwardly Rectifying KW - RNA, Messenger KW - Receptors, Drug KW - Recombinant Fusion Proteins KW - Sulfonylurea Receptors KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Camk2a protein, mouse KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Calcium-Calmodulin-Dependent Protein Kinases -- genetics KW - Animals KW - Kainic Acid -- pharmacology KW - Gene Expression KW - Mice KW - Mice, Transgenic KW - Promoter Regions, Genetic KW - Kainic Acid -- adverse effects KW - Cell Death KW - Excitatory Amino Acid Agonists -- pharmacology KW - Excitatory Amino Acid Agonists -- adverse effects KW - Excitatory Postsynaptic Potentials -- physiology KW - Cricetinae KW - Seizures -- chemically induced KW - Receptors, Drug -- genetics KW - Prosencephalon -- metabolism KW - Neurons -- drug effects KW - Potassium Channels -- genetics KW - Potassium Channels -- physiology KW - Seizures -- prevention & control KW - Receptors, Drug -- physiology KW - Recombinant Fusion Proteins -- physiology KW - Seizures -- mortality KW - Neurons -- cytology KW - Neurons -- physiology KW - Recombinant Fusion Proteins -- genetics KW - ATP-Binding Cassette Transporters KW - Prosencephalon -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76972112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Mice+transgenically+overexpressing+sulfonylurea+receptor+1+in+forebrain+resist+seizure+induction+and+excitotoxic+neuron+death.&rft.au=Hern%C3%A1ndez-S%C3%A1nchez%2C+C%3BBasile%2C+A+S%3BFedorova%2C+I%3BArima%2C+H%3BStannard%2C+B%3BFernandez%2C+A+M%3BIto%2C+Y%3BLeRoith%2C+D&rft.aulast=Hern%C3%A1ndez-S%C3%A1nchez&rft.aufirst=C&rft.date=2001-03-13&rft.volume=98&rft.issue=6&rft.spage=3549&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-03-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Physiol. 1999 Dec 1;521 Pt 2:337-50 [10581306] J Biol Chem. 1999 Jun 25;274(26):18261-70 [10373428] Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1293-8 [10655524] J Neuroendocrinol. 2000 Sep;12(9):833-42 [10971808] Nature. 1983 Sep 8-14;305(5930):147-8 [6310409] Neuroscience. 1985 Feb;14(2):375-403 [2859548] Eur J Pharmacol. 1989 Jan 17;159(3):329-30 [2920778] Brain Res. 1989 May 1;486(1):159-64 [2497930] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7451-5 [2477843] Science. 1990 Feb 16;247(4944):852-4 [2305257] Cell Signal. 1990;2(3):197-214 [2119205] Neuroscience. 1990;37(1):55-60 [1978742] Br J Pharmacol. 1990 Nov;101(3):531-40 [2127550] Mol Cell Biol. 1991 Jun;11(6):3070-4 [2038318] J Neurosci. 1992 Aug;12(8):3004-9 [1494943] Naunyn Schmiedebergs Arch Pharmacol. 1993 Jul;348(1):113-7 [8377835] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9431-5 [8415718] Neuroreport. 1993 Oct 25;5(1):90-2 [7904192] Science. 1995 Apr 21;268(5209):423-6 [7716547] Cell. 1995 Jun 16;81(6):891-904 [7781066] Science. 1995 Nov 17;270(5239):1166-70 [7502040] FEBS Lett. 1995 Dec 27;377(3):338-44 [8549751] Neuron. 1996 May;16(5):1011-7 [8630239] Eur J Pharmacol. 1996 May 23;304(1-3):37-47 [8813582] Diabetes. 1996 Oct;45(10):1439-45 [8826984] J Physiol. 1996 Oct 1;496 ( Pt 1):155-64 [8910204] Biochemistry. 1996 Nov 26;35(47):14793-9 [8942641] Endocrinology. 1997 Feb;138(2):705-11 [9003005] FEBS Lett. 1997 Jan 13;401(1):59-64 [9003806] J Neurophysiol. 1997 Jan;77(1):378-85 [9120578] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4103-8 [9108112] J Physiol. 1997 Mar 15;499 ( Pt 3):715-20 [9130167] Nature. 1997 May 8;387(6629):179-83 [9144288] Eur J Neurosci. 1997 Apr;9(4):760-9 [9153582] Neuron. 1997 May;18(5):827-38 [9182806] J Neurochem. 1997 Oct;69(4):1570-9 [9326286] Pflugers Arch. 1998 Apr;435(5):595-603 [9479011] Lab Anim Sci. 1998 Feb;48(1):34-7 [9517887] J Physiol. 1998 Jul 15;510 ( Pt 2):441-53 [9705995] J Physiol. 1999 Jan 15;514 ( Pt 2):327-41 [9852317] Mol Chem Neuropathol. 1998 Aug-Dec;35(1-3):39-59 [10343970] J Cereb Blood Flow Metab. 1999 Dec;19(12):1296-308 [10598933] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The targeting pathway of Escherichia coli presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal AN - 17815782; 4856164 AB - Previous studies have demonstrated that presecretory proteins such as maltose binding protein (MBP) and outer membrane protein A (OmpA) are targeted to the Escherichia coli inner membrane by the molecular chaperone SecB, but that integral membrane proteins are targeted by the signal recognition particle (SRP). In vitro studies have suggested that trigger factor binds to a sequence near the N terminus of the mature region of OmpA and shunts the protein into the SecB pathway by blocking an interaction between SRP and the signal peptide. By contrast, we have found that the targeting pathway of a protein under physiological conditions is dictated by the composition of its targeting signal. Replacement of the MBP or OmpA signal peptide with the first transmembrane segment of AcrB abolished the dependence on SecB for transport and rerouted both proteins into the SRP targeting pathway. More modest alterations of the MBP signal peptide that simply increase its hydrophobicity also promoted SRP binding. Furthermore, we obtained evidence that SRP has a low affinity for typical signal peptides in vivo. These results imply that different classes of E. coli proteins are targeted by distinct pathways because bacterial SRP binds to a more restricted range of targeting signals than its eukaryotic counterpart. JF - Proceedings of the National Academy of Sciences, USA AU - Lee, H C AU - Bernstein, H D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9D-20, Bethesda, MD 20892-1810, harris_bernstein@nih.gov Y1 - 2001/03/13/ PY - 2001 DA - 2001 Mar 13 SP - 3471 EP - 3476 VL - 98 IS - 6 SN - 0027-8424, 0027-8424 KW - targeting KW - OmpA protein KW - maltose-binding protein KW - Microbiology Abstracts B: Bacteriology KW - Cell membranes KW - Escherichia coli KW - Hydrophobicity KW - Membrane proteins KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17815782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=The+targeting+pathway+of+Escherichia+coli+presecretory+and+integral+membrane+proteins+is+specified+by+the+hydrophobicity+of+the+targeting+signal&rft.au=Lee%2C+H+C%3BBernstein%2C+H+D&rft.aulast=Lee&rft.aufirst=H&rft.date=2001-03-13&rft.volume=98&rft.issue=6&rft.spage=3471&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Membrane proteins; Cell membranes; Hydrophobicity ER - TY - JOUR T1 - Ca super(2+) signalling between single L-type Ca super(2+) channels and ryanodine receptors in heart cells AN - 856753971; 13743295 AB - Ca super(2+)-induced Ca super(2+) release is a general mechanism that most cells use to amplify Ca super(2+) signals. In heart cells, this mechanism is operated between voltage-gated L-type Ca super(2+) channels (LCCs) in the plasma membrane and Ca super(2+) release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The Ca super(2+) influx through LCCs traverses a cleft of roughly 12nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release Ca super(2+) in the form of Ca super(2+) sparks. Here we determine the kinetics, fidelity and stoichiometry of coupling between LCCs and ryanodine receptors. We show that the local Ca super(2+) signal produced by a single opening of an LCC, named a 'Ca super(2+) sparklet', can trigger about 4-6 ryanodine receptors to generate a Ca super(2+) spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. This optical analysis of single-channel communication affords a powerful means for elucidating Ca super(2+)-signalling mechanisms at the molecular level. JF - Nature AU - Wang, Shi-Qiang AU - Song, Long-Sheng AU - Lakatta, Edward G AU - Cheng, Heping AD - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA PY - 2001 SP - 592 EP - 596 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 410 IS - 6828 SN - 0028-0836, 0028-0836 KW - Aqualine Abstracts; Water Resources Abstracts; Calcium & Calcified Tissue Abstracts KW - Heart KW - Cell surface KW - Sarcoplasmic reticulum KW - Membranes KW - Communication KW - Calcium channels (voltage-gated) KW - Stochasticity KW - Channels KW - Fidelity KW - Calcium influx KW - Ryanodine receptors KW - Calcium release channels KW - Plasma membranes KW - Kinetics KW - Calcium channels (L-type) KW - Calcium channels KW - Calcium signalling KW - AQ 00001:Water Resources and Supplies KW - T 2010:Muscle KW - SW 0540:Properties of water UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856753971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Ca+super%282%2B%29+signalling+between+single+L-type+Ca+super%282%2B%29+channels+and+ryanodine+receptors+in+heart+cells&rft.au=Wang%2C+Shi-Qiang%3BSong%2C+Long-Sheng%3BLakatta%2C+Edward+G%3BCheng%2C+Heping&rft.aulast=Wang&rft.aufirst=Shi-Qiang&rft.date=2001-03-09&rft.volume=410&rft.issue=6828&rft.spage=592&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35069083 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - Heart; Sarcoplasmic reticulum; Cell surface; Communication; Calcium channels (voltage-gated); Stochasticity; Ryanodine receptors; Calcium influx; Fidelity; Calcium release channels; Plasma membranes; Calcium channels (L-type); Kinetics; Calcium channels; Calcium signalling; Channels; Membranes DO - http://dx.doi.org/10.1038/35069083 ER - TY - JOUR T1 - The Venus's-flytrap and cysteine-rich domains of the human Ca2+ receptor are not linked by disulfide bonds. AN - 70881324; 11238442 AB - The extracellular N-terminal domain of the human Ca(2+) receptor (hCaR) consists of a Venus's-flytrap (VFT) domain and a cysteine-rich (Cys-rich) domain. We have shown earlier that the Cys-rich domain is critical for signal transmission from the VFT domain to the seven-transmembrane domain. The VFT domain contains 10 cysteines: two of them (Cys(129) and Cys(131)) were identified as involved in intermolecular disulfide bonds necessary for homodimerization, and six others (Cys(60)-Cys(101), Cys(358)-Cys(395), and Cys(437)-Cys(449)) are predicted to form three intramolecular disulfide bonds. The Cys-rich domain contains nine cysteines, the involvement of which in disulfide bond formation has not been defined. In this work, we asked whether the remaining cysteines in the hCaR VFT, namely Cys(236) and Cys(482), form disulfide bond(s) with cysteines in the Cys-rich domain. We constructed mutant hCaRs with a unique tobacco etch virus (TEV) protease recognition site inserted between the VFT domain and the Cys-rich domain. These mutant hCaRs remain fully functional compared with the wild type hCaR. After TEV protease digestion of the mutant hCaR proteins, dimers of the VFT were identified on Western blot under nonreducing conditions. We concluded that there is no disulfide bond between the VFT and the Cys-rich domains in the hCaR. JF - The Journal of biological chemistry AU - Hu, J AU - Reyes-Cruz, G AU - Goldsmith, P K AU - Spiegel, A M AD - Molecular Pathophysiology Section, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. jianxinh@intra.niddk.nih.gov Y1 - 2001/03/09/ PY - 2001 DA - 2001 Mar 09 SP - 6901 EP - 6904 VL - 276 IS - 10 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - Disulfides KW - Protein Sorting Signals KW - Glutamic Acid KW - 3KX376GY7L KW - Endopeptidases KW - EC 3.4.- KW - TEV protease KW - Valine KW - HG18B9YRS7 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Immunoblotting KW - Dose-Response Relationship, Drug KW - Dimerization KW - Humans KW - Glutamic Acid -- chemistry KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Transfection KW - Endopeptidases -- metabolism KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Valine -- chemistry KW - Cell Line KW - Protein Conformation KW - Cysteine -- chemistry KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70881324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+Venus%27s-flytrap+and+cysteine-rich+domains+of+the+human+Ca2%2B+receptor+are+not+linked+by+disulfide+bonds.&rft.au=Hu%2C+J%3BReyes-Cruz%2C+G%3BGoldsmith%2C+P+K%3BSpiegel%2C+A+M&rft.aulast=Hu&rft.aufirst=J&rft.date=2001-03-09&rft.volume=276&rft.issue=10&rft.spage=6901&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-beta type II receptor expression. AN - 77072409; 11313868 AB - Transcriptional repression of the TGF-beta type II receptor (RII) is one of the mechanisms leading to TGF-beta resistance. The newly identified epithelium-specific ets transcription factor ERT/ESX/ELF-3/ESE-1/jen binds to the TGF-beta RII promoter and induces promoter activity. The human gastric cancer cell lines, which show undetectable level of TGF-beta RII mRNA, do not express ERT mRNA. To study the molecular mechanisms of loss of ERT expression, we have cloned and characterized the human ERT promoter. DNA transfection experiments and electrophoretic mobility shift assays have revealed the existence of a distinct enhancer element (-186 to -177) which we named ESE (ERT promoter specific element). Deletion of the ESE markedly decreased expression of the target gene. ESE interacts with two distinct nuclear protein complexes, at least one of which appears to be inactivated in a cell line which does not express the ERT mRNA, compared to a cell line expressing the ERT mRNA. These results suggest the possibility that inactivation of the sequence-specific DNA binding protein to the region from -186 to -177 contributes to the loss of ERT expression, leading to the loss of TGF-beta type II receptor mRNA in human gastric cancer cell lines. JF - Oncogene AU - Park, S H AU - Kim, Y S AU - Park, B K AU - Hougaard, S AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 2001/03/08/ PY - 2001 DA - 2001 Mar 08 SP - 1235 EP - 1245 VL - 20 IS - 10 SN - 0950-9232, 0950-9232 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - ELF3 protein, human KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transcription Factors KW - Transforming Growth Factor beta KW - Luciferases KW - EC 1.13.12.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Blotting, Northern KW - Humans KW - Gene Expression KW - Luciferases -- metabolism KW - RNA, Messenger -- genetics KW - Gene Amplification KW - Gene Deletion KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Electrophoresis, Agar Gel KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Promoter Regions, Genetic -- genetics KW - DNA, Neoplasm -- biosynthesis KW - DNA Primers -- chemistry KW - Stomach Neoplasms -- metabolism KW - Transcription Factors -- metabolism KW - Stomach Neoplasms -- genetics KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77072409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Sequence-specific+enhancer+binding+protein+is+responsible+for+the+differential+expression+of+ERT%2FESX%2FELF-3%2FESE-1%2Fjen+gene+in+human+gastric+cancer+cell+lines%3A+Implication+for+the+loss+of+TGF-beta+type+II+receptor+expression.&rft.au=Park%2C+S+H%3BKim%2C+Y+S%3BPark%2C+B+K%3BHougaard%2C+S%3BKim%2C+S+J&rft.aulast=Park&rft.aufirst=S&rft.date=2001-03-08&rft.volume=20&rft.issue=10&rft.spage=1235&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of mucous differentiation and mucin gene expression in the tracheobronchial epithelium. AN - 76969962; 11246122 AB - The goal of our studies is to elucidate mechanisms that control and modulate mucous differentiation and mucin gene expression in the conducting airways. We used cultures of normal human tracheobronchial epithelial (NHTBE) cells that were shown to secrete two major airway mucins, namely MUC5AC and MUC5B as well as several other secretory products. Mucous differentiation and expression of MUC2, MUC5AC, MUC5B and MUC7, but not MUCi, MUC4, and MUC8 mucin genes, were shown to be retinoic acid- (RA) or retinol-dependent. We found that RA control of mucin genes was mediated by the retinoid acid receptors RAR alpha and, to a lesser extent, by RAR gamma. Our studies also showed that other important bioregulators such as thyroid hormone (T3) and epidermal growth factor (EGF) modulate basal expression of mucin genes, interacting with RA in a concentration-dependent manner. T3, which binds to thyroid receptors (TRs) belonging to the same superfamily of steroid hormone nuclear receptors as the RARs, inhibits mucin gene expression, particularly MUC5AC. One possible mechanism of this T3 effect is downregulation of RAR proteins, which are critical for mucin gene expression. However, we also found that T3 inhibits MUC5AC transcription.EGF, which had previously been shown to stimulate mucin expression and mucin secretion in cultured rat tracheal epithelial (RTE) cells, inhibited mucin secretion in human bronchial epithelial cell cultures. This effect was EGF concentration- and time-dependent and was progressively abolished by increasing the RA concentration. Subsequent studies suggested that the inhibitory effects of high concentrations of EGF may result from selective reduction of MUC5AC expression. These studies thus point to potentially important species differences in the mechanisms regulating mucous production, and they also confirm previous findings indicating differential regulation of MUC5AC and MUC5B gene expression. JF - Toxicology AU - Gray, T AU - Koo, J S AU - Nettesheim, P AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. grayt@niehs.nih.gov Y1 - 2001/03/07/ PY - 2001 DA - 2001 Mar 07 SP - 35 EP - 46 VL - 160 IS - 1-3 SN - 0300-483X, 0300-483X KW - Mucins KW - 0 KW - RNA, Messenger KW - Receptors, Retinoic Acid KW - Triiodothyronine KW - 06LU7C9H1V KW - Tretinoin KW - 5688UTC01R KW - Epidermal Growth Factor KW - 62229-50-9 KW - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Tretinoin -- pharmacology KW - Drug Interactions KW - Triiodothyronine -- pharmacology KW - Respiratory Mucosa -- cytology KW - Dose-Response Relationship, Drug KW - Humans KW - Respiratory Mucosa -- drug effects KW - Epidermal Growth Factor -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Blotting, Western KW - Respiratory Mucosa -- metabolism KW - RNA, Messenger -- metabolism KW - Cell Line KW - Gene Expression Regulation -- physiology KW - Mucins -- genetics KW - Cell Differentiation -- physiology KW - Bronchi -- cytology KW - Mucins -- metabolism KW - Gene Expression Regulation -- drug effects KW - Trachea -- metabolism KW - Trachea -- cytology KW - Bronchi -- metabolism KW - Bronchi -- drug effects KW - Trachea -- drug effects KW - Cell Differentiation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76969962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Regulation+of+mucous+differentiation+and+mucin+gene+expression+in+the+tracheobronchial+epithelium.&rft.au=Gray%2C+T%3BKoo%2C+J+S%3BNettesheim%2C+P&rft.aulast=Gray&rft.aufirst=T&rft.date=2001-03-07&rft.volume=160&rft.issue=1-3&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity. AN - 76966487; 11245929 AB - DNA damage has been documented in neurodegenerative conditions ranging from Alzheimer's disease to stroke. DNA-dependent protein kinase (DNA-PK) is involved in V(D)J recombination and DNA double strand break repair, and may play a role in cell death induced by DNA damage. We now report that cultured hippocampal neurons from severe combined immunodeficient (scid) mice which lack DNA-PK activity are hypersensitive to apoptosis induced by exposure to topoisomerase inhibitors, amyloid beta peptide (A beta) and glutamate. A similar increased vulnerability of hippocampal CA1 and CA3 neurons was observed in adult scid mice after kainate-induced seizures. Our results suggest that DNA-PK activity is important for neuron survival under conditions that may occur in neurological disorders. JF - Brain research. Molecular brain research AU - Culmsee, C AU - Bondada, S AU - Mattson, M P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2001/03/05/ PY - 2001 DA - 2001 Mar 05 SP - 257 EP - 262 VL - 87 IS - 2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Peptides KW - 0 KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Neurotoxins KW - Nucleic Acid Synthesis Inhibitors KW - Topoisomerase I Inhibitors KW - Glutamic Acid KW - 3KX376GY7L KW - Etoposide KW - 6PLQ3CP4P3 KW - DNA-Activated Protein Kinase KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Etoposide -- pharmacology KW - Animals KW - Camptothecin -- pharmacology KW - Epilepsy -- metabolism KW - Mice KW - Glutamic Acid -- pharmacology KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Oxidative Stress -- physiology KW - Amyloid beta-Peptides -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Alzheimer Disease -- metabolism KW - Mice, SCID KW - DNA Damage -- physiology KW - Protein-Serine-Threonine Kinases -- deficiency KW - Hippocampus -- cytology KW - Neurotoxins -- pharmacology KW - Neurons -- enzymology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76966487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Hippocampal+neurons+of+mice+deficient+in+DNA-dependent+protein+kinase+exhibit+increased+vulnerability+to+DNA+damage%2C+oxidative+stress+and+excitotoxicity.&rft.au=Culmsee%2C+C%3BBondada%2C+S%3BMattson%2C+M+P&rft.aulast=Culmsee&rft.aufirst=C&rft.date=2001-03-05&rft.volume=87&rft.issue=2&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-28 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of oxidative stress in developmental and reproductive toxicity of tamoxifen. AN - 77004858; 11270620 AB - The antiestrogen tamoxifen (TAM) is widely used as a drug against breast cancer and is currently being tested as a chemopreventive agent. However, a number of studies showed genotoxic and carcinogenic effects of TAM. These effects are thought to be related to oxygen radical overproduction which occurs during TAM metabolic activation. There is no evidence, thus far, on TAM toxicity to embryos and gametes. The present study was designed to elucidate the mechanisms of TAM-induced developmental, reproductive and cytogenetic toxicity towards sea urchin (SU) embryos with regard to the possibility of TAM-initiated oxidative stress. Embryo cultures from SU were subjected to long-term (throughout embryogenesis) or short-term (two hours) incubation with TAM at concentrations from 10(-8) to 10(-5) M. The experiments on TAM-induced toxicity to gametes were carried out with SU sperm, or unfertilized eggs, suspended in TAM (10(-8) to 10(-6) M). To assess the effects of TAM to embryos or to gametes, developmental defects, embryonic mortality, fertilization success, and cytogenetic abnormalities were scored. Oxidative damage to DNA and lipids was detected by measurements of 8OHdG levels and lipid peroxidation, respectively. Reactive oxygen species (ROS) production by eggs and embryos was recorded by luminol-dependent chemiluminescence (LDCL) and cytochrome c reduction methods. The changes in activities of SU superoxide dismutase (SOD) and catalase were also evaluated. TAM exerted: a) early embryonic mortality to exposed embryos and to the offspring of exposed eggs; b) developmental defects to the offspring of exposed sperm; c) decrease in sperm fertilization success, and d) cytogenetic effects in the offspring of exposed sperm or eggs. These morphological effects corresponded to the state of oxidative stress in SU embryos (increased oxidative damage to DNA and lipids and induction of antioxidant enzymes). Since TAM did increase significantly ROS production by embryos, it is suggested that TAM may be metabolically activated by SU embryonic oxidases and peroxidases, which in turn could be induced by TAM. The present study provides further support to the utilization of the SU system as a useful model to help elucidate mechanisms of chemical teratogenesis and carcinogenesis. JF - Life sciences AU - Pagano, G AU - de Biase, A AU - Deeva, I B AU - Degan, P AU - Doronin, Y K AU - Iaccarino, M AU - Oral, R AU - Trieff, N M AU - Warnau, M AU - Korkina, L G AD - Italian National Cancer Institute, G. Pascale Foundation, Naples. gbpagano@tin.it Y1 - 2001/03/02/ PY - 2001 DA - 2001 Mar 02 SP - 1735 EP - 1749 VL - 68 IS - 15 SN - 0024-3205, 0024-3205 KW - Estrogen Antagonists KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Superoxides KW - 11062-77-4 KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Catalase -- metabolism KW - Animals KW - Superoxides -- metabolism KW - Luminescent Measurements KW - Dose-Response Relationship, Drug KW - Lipid Peroxidation -- drug effects KW - Superoxide Dismutase -- metabolism KW - Tamoxifen -- toxicity KW - Estrogen Antagonists -- toxicity KW - Embryo, Nonmammalian -- physiology KW - Reproduction -- drug effects KW - Oxidative Stress KW - Sea Urchins -- embryology KW - Embryo, Nonmammalian -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77004858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=The+role+of+oxidative+stress+in+developmental+and+reproductive+toxicity+of+tamoxifen.&rft.au=Pagano%2C+G%3Bde+Biase%2C+A%3BDeeva%2C+I+B%3BDegan%2C+P%3BDoronin%2C+Y+K%3BIaccarino%2C+M%3BOral%2C+R%3BTrieff%2C+N+M%3BWarnau%2C+M%3BKorkina%2C+L+G&rft.aulast=Pagano&rft.aufirst=G&rft.date=2001-03-02&rft.volume=68&rft.issue=15&rft.spage=1735&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tetraplex formation by the progressive myoclonus epilepsy type-1 repeat: implications for instability in the repeat expansion diseases. AN - 70689423; 11240124 AB - The repeat expansion diseases are a group of genetic disorders resulting from an increase in size or expansion of a specific array of tandem repeats. It has been suggested that DNA secondary structures are responsible for this expansion. If this is so, we would expect that all unstable repeats should form such structures. We show here that the unstable repeat that causes progressive myoclonus epilepsy type-1 (EPM1), like the repeats associated with other diseases in this category, forms a variety of secondary structures. However, EPM1 is unique in that tetraplexes are the only structures likely to form in long unpaired repeat tracts under physiological conditions. JF - FEBS letters AU - Saha, T AU - Usdin, K AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, Building 8, Room 202, National Institutes of Health, 8 CENTER DR MSC 0830, Bethesda, MD 20892-0830, USA. Y1 - 2001/03/02/ PY - 2001 DA - 2001 Mar 02 SP - 184 EP - 187 VL - 491 IS - 3 SN - 0014-5793, 0014-5793 KW - Acids KW - 0 KW - Cytosine Nucleotides KW - Sulfuric Acid Esters KW - Guanosine KW - 12133JR80S KW - Potassium Chloride KW - 660YQ98I10 KW - DNA KW - 9007-49-2 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Diethyl Pyrocarbonate KW - LMR3LZG146 KW - Index Medicus KW - Acids -- chemistry KW - G-Quadruplexes KW - Electrophoresis, Polyacrylamide Gel KW - Potassium Chloride -- pharmacology KW - Temperature KW - Sulfuric Acid Esters -- pharmacology KW - Unverricht-Lundborg Syndrome -- genetics KW - Circular Dichroism KW - Guanosine -- metabolism KW - Promoter Regions, Genetic KW - Diethyl Pyrocarbonate -- pharmacology KW - Guanosine -- chemistry KW - Hydrogen Bonding KW - Nucleic Acid Conformation -- drug effects KW - Cytosine Nucleotides -- chemistry KW - Cytosine Nucleotides -- metabolism KW - Trinucleotide Repeat Expansion -- genetics KW - DNA -- chemistry KW - Myoclonic Epilepsies, Progressive -- genetics KW - Trinucleotide Repeat Expansion -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70689423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Tetraplex+formation+by+the+progressive+myoclonus+epilepsy+type-1+repeat%3A+implications+for+instability+in+the+repeat+expansion+diseases.&rft.au=Saha%2C+T%3BUsdin%2C+K&rft.aulast=Saha&rft.aufirst=T&rft.date=2001-03-02&rft.volume=491&rft.issue=3&rft.spage=184&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impairment of eyeblink classical conditioning in progressive supranuclear palsy. AN - 85365567; pmid-11295776 AB - In a previous study we showed that learning in eyeblink classical conditioning (EBCC) is normal in Parkinson's disease (PD) and that the serial reaction time task (SRTT) is only marginally impaired. Since pathological lesions are more widespread in the atypical parkinsonian disorder of progressive supranuclear palsy (PSP) than in PD, we hypothesized that PSP patients may show more profound deficits in the EBCC and SRTT learning tasks. We therefore investigated EBCC with a delay and two trace paradigms, an SRTT and the California Verbal Learning Test (CVLT) in eight patients with PSP and an age-matched control group. In all EBCC paradigms, we found a significant difference between groups with no significant learning in PSP patients. In the SRTT, implicit learning may have been impaired, but verbal and manual sequence recall were only marginally impaired. Verbal memory was significantly worse in PSP patients than in the control group. Our study shows a dissociated pattern of learning abilities in PSP, where the EBCC as a measure of implicit learning is impaired, the explicit sequence detection in the SRTT is relatively preserved, and the verbal memory impaired. We hypothesize that the PSP patients' deficits in EBCC learning may be due to lesions of deep cerebellar nuclei. There may be a clinical role for EBCC in distinguishing PD and PSP patients.Copyright 2001 Movement Disorder Society. JF - Movement disorders : official journal of the Movement Disorder Society AU - Sommer, M AU - Grafman, J AU - Litvan, I AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 240 EP - 251 VL - 16 IS - 2 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Aged KW - *Blinking: physiology KW - Cerebellar Nuclei: physiopathology KW - *Conditioning, Classical: physiology KW - Electromyography KW - Female KW - Humans KW - Learning Disorders: diagnosis KW - Male KW - Memory Disorders: diagnosis KW - Middle Aged KW - Psychological Tests KW - Reaction Time KW - Sensory Thresholds: physiology KW - Supranuclear Palsy, Progressive: diagnosis KW - *Supranuclear Palsy, Progressive: physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85365567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Impairment+of+eyeblink+classical+conditioning+in+progressive+supranuclear+palsy.&rft.au=Sommer%2C+M%3BGrafman%2C+J%3BLitvan%2C+I%3BHallett%2C+M&rft.aulast=Sommer&rft.aufirst=M&rft.date=2001-03-01&rft.volume=16&rft.issue=2&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Supracricoid laryngectomy with CHEP: functional results and outcome. AN - 85355530; pmid-11240986 AB - To assess whether supracricoid laryngectomy with cricohiodoepiglottopexy could successfully reach the cure and preserve the voice in glottic laryngeal cancer, we studied 27 patients with T2/T3 squamous cell carcinoma of the larynx treated in our institution with cricohiodoepiglottopexy.A retrospective analysis has been carried out between 1995 through 1997. We classified 11 patients as T2N0M0 and 16 patients as T3N0M0. Nineteen patients had bilateral selective lateral neck dissection, 3 patients had unilateral lateral neck dissection, and 5 patients had undissected neck. Survival was analyzed under the Kaplan-Meyer method.Five patients had postoperative complications, 2 were treated with a total laryngectomy. The remaining 25 patients kept the normal airway, swallowing, and speech. None of the patients in the neck dissection group had neck metastasis. Two patients had recurrences, 1 with local recurrence was treated with a total laryngectomy and is alive without disease; the other patient had neck recurrence, was treated with radical neck dissection plus radiotherapy, and is dead of the disease. One patient had a second tumor in oropharynx treated with palliative radiotherapy and is dead of the disease. Three years disease-free survival was 75% for T2 and 79% for T3.This technique is useful in the treatment of selected cases of T3/T2 glottic cancer regarding the extent of disease. The incidence of complications in need of a complete laryngectomy does not compromise the functionality of this technique. The survival is comparable to patients who submitted to total laryngectomy and near-total laryngectomy, regarding the extent of the lesion. JF - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery AU - Lima, R A AU - Freitas, E Q AU - Kligerman, J AU - Dias, F L AU - Barbosa, M M AU - Sa, G M AU - Santos, I C AU - Farias, T AD - Head and Neck Service, Hospital do Cancer, National Cancer Institute/INCA, Rio de Janeiro, Brazil. rlima@iis.com.br Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 258 EP - 260 VL - 124 IS - 3 SN - 0194-5998, 0194-5998 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Aged KW - Carcinoma, Squamous Cell: mortality KW - *Carcinoma, Squamous Cell: surgery KW - *Cricoid Cartilage: surgery KW - Disease-Free Survival KW - *Epiglottis: surgery KW - Female KW - *Glottis: surgery KW - Humans KW - *Hyoid Bone: surgery KW - Incidence KW - Laryngeal Neoplasms: mortality KW - *Laryngeal Neoplasms: surgery KW - *Laryngectomy: methods KW - Male KW - Middle Aged KW - Neoplasm Staging KW - Postoperative Complications: epidemiology KW - Treatment Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85355530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--head+and+neck+surgery+%3A+official+journal+of+American+Academy+of+Otolaryngology-Head+and+Neck+Surgery&rft.atitle=Supracricoid+laryngectomy+with+CHEP%3A+functional+results+and+outcome.&rft.au=Lima%2C+R+A%3BFreitas%2C+E+Q%3BKligerman%2C+J%3BDias%2C+F+L%3BBarbosa%2C+M+M%3BSa%2C+G+M%3BSantos%2C+I+C%3BFarias%2C+T&rft.aulast=Lima&rft.aufirst=R&rft.date=2001-03-01&rft.volume=124&rft.issue=3&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--head+and+neck+surgery+%3A+official+journal+of+American+Academy+of+Otolaryngology-Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Recommendations for cancer prevention trials using potentially ototoxic test agents. AN - 85275308; pmid-11250994 AB - PURPOSE: Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill. MATERIALS AND METHODS: Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging. Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations. RESULTS: Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents. CONCLUSION: These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care. JF - Journal of Clinical Oncology AU - Shotland, L I AU - Ondrey, F G AU - Mayo, K A AU - Viner, J L AD - Hearing Section, Neuro-Otology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2001 SP - 1658 EP - 1663 VL - 19 IS - 6 SN - 0732-183X, 0732-183X KW - Age Factors KW - Support, U.S. Gov't, P.H.S. KW - Audiometry KW - Antineoplastic Agents KW - Human KW - Animal KW - Aged KW - Monitoring, Physiologic KW - Patient Selection KW - Deafness KW - Neoplasms KW - Adult KW - Practice Guidelines KW - Middle Age KW - Chemoprevention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85275308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Oncology&rft.atitle=Recommendations+for+cancer+prevention+trials+using+potentially+ototoxic+test+agents.&rft.au=Shotland%2C+L+I%3BOndrey%2C+F+G%3BMayo%2C+K+A%3BViner%2C+J+L&rft.aulast=Shotland&rft.aufirst=L&rft.date=2001-03-01&rft.volume=19&rft.issue=6&rft.spage=1658&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Action of 2,3-butanedione monoxime on capacitance and electromotility of guinea-pig cochlear outer hair cells. AN - 85231038; pmid-11251049 AB - 1. Whole-cell patch-clamp recordings were obtained from isolated cochlear outer hair cells (OHCs) while applying 2,3-butanedione monoxime (BDM) by pressure. BDM (5 mM) shifted the range of voltage sensitivity of membrane capacitance and cell length in the hyperpolarised direction by -49.6 +/- 4.0 mV (n = 12; mean +/- S.E.M.), without appreciable effects on membrane conductance. The shift was completely reversible and dose dependent, with a Hill coefficient of 1.8 /- 0.4 and a half-maximal dose of 3.0 +/- 0.8 mM (values +/- S.D). 2. The shift of the capacitance curve was also reproducible in cells whose natural turgor had been removed. BDM had no detectable effect on the capacitance of Deiters' cells, a non-sensory cell type of the organ of Corti. 3. The effect of BDM on membrane capacitance was faster than that of salicylate. At similar saturating concentrations (20 mM), the time constant of the capacitance changes was 1.8 +/- 0.3 s (n = 3) for salicylate and 0.75 +/- 0.06 s (n = 3) for BDM. The recovery periods were 13 +/- 1 s and 1.7 +/- 0.4 s, respectively (means +/- S.E.M.). 4. The effect of BDM, a known inorganic phosphatase, was compared to the effects of okadaic acid, trifluoperazine and W-7, which are commonly used in studies of protein phosphorylation. Incubation of OHCs with okadaic acid (1 microM, 30-60 min) shifted the voltage sensitivity of the membrane capacitance in the hyperpolarised direction. Incubation with trifluoperazine (30 microM) and W-7 (150 microM) shifted it in the opposite, depolarised direction. BDM induced hyperpolarising shifts even in the presence of W-7. 5. Simultaneous measurement of membrane capacitance and intracellular free Ca2+ concentration ([Ca2+]i) showed that BDM action on OHC voltage-dependent capacitance and electromotility is not mediated by changes of [Ca2+]i. 6. Our results suggest that: (a) the effects of BDM are unrelated to its inorganic phosphatase properties, cell turgor conditions or Ca2+ release from intracellular stores; and (b) BDM may target directly the voltage sensor of the OHC membrane motor protein. JF - The Journal of Physiology AU - Frolenkov, G I AU - Mammano, F AU - Kachar, B AD - Section on Structural Cell Biology, Laboratory of Cellular Biology, NIDCD-NIH, Bethesda, MD 20892-4163, USA. PY - 2001 SP - 667 EP - 676 VL - 531 IS - Pt 3 SN - 0022-3751, 0022-3751 KW - Cell Movement KW - Osmolar Concentration KW - Support, U.S. Gov't, P.H.S. KW - Calcium KW - Electric Conductivity KW - Guinea Pigs KW - Intracellular Membranes KW - Salicylates KW - Animal KW - Electrophysiology KW - Diacetyl KW - Comparative Study KW - Phosphorylation KW - Hair Cells, Outer KW - Proteins KW - Support, Non-U.S. Gov't KW - Pressure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85231038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Physiology&rft.atitle=Action+of+2%2C3-butanedione+monoxime+on+capacitance+and+electromotility+of+guinea-pig+cochlear+outer+hair+cells.&rft.au=Frolenkov%2C+G+I%3BMammano%2C+F%3BKachar%2C+B&rft.aulast=Frolenkov&rft.aufirst=G&rft.date=2001-03-01&rft.volume=531&rft.issue=Pt+3&rft.spage=667&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Physiology&rft.issn=00223751&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Conjoint and extended neural networks for the computation of speech codes: the neural basis of selective impairment in reading words and pseudowords. AN - 85219909; pmid-11230098 AB - The computation of speech codes (i.e. phonology) is an important aspect of word reading. Understanding the neural systems and mech- anisms underlying phonological processes provides a foundation for the investigation of language in the brain. We used high-resolution three-dimensional positron emission tomography (PET) to investigate neural systems essential for phonological processes. The burden of neural activities on the computation of speech codes was maximized by three rhyming tasks (rhyming words, pseudowords and words printed in mixed letter cases). Brain activation patterns associated with these tasks were compared with those of two baseline tasks involving visual feature detection. Results suggest strong left lateralized epicenters of neural activity in rhyming irrespective of gender. Word rhyming activated the same brain regions engaged in pseudoword rhyming, suggesting conjoint neural networks for phonological processing of words and pseudowords. However, pseudoword rhyming induced the largest change in cerebral blood flow and activated more voxels in the left posterior prefrontal regions and the left inferior occipital-temporal junction. In addition, pseudoword rhyming activated the left supramarginal gyrus, which was not apparent in word rhyming. These results suggest that rhyming pseudowords requires active participation of extended neural systems and networks not observed for rhyming words. The implications of the results on theories and models of visual word reading and on selective reading dysfunctions after brain lesions are discussed. JF - Cerebral Cortex AU - Xu B AU - Grafman, J AU - Gaillard, W D AU - Ishii, K AU - Vega-Bermudez, F AU - Pietrini, P AU - Reeves-Tyer, P AU - DiCamillo, P AU - Theodore, W AD - Epilepsy Research Branch and Cognitive Neuroscience Section, NINDS, the National Institutes of Health, Bethesda, MD 20892, USA. PY - 2001 SP - 267 EP - 277 VL - 11 IS - 3 SN - 1047-3211, 1047-3211 KW - Analysis of Variance KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Cerebellum KW - Prefrontal Cortex KW - Nerve Net KW - Photic Stimulation KW - Temporal Lobe KW - Adult KW - Tomography, Emission-Computed KW - Female KW - Male KW - Reaction Time KW - Occipital Lobe KW - Brain Mapping KW - Reading KW - Phonetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cerebral+Cortex&rft.atitle=Conjoint+and+extended+neural+networks+for+the+computation+of+speech+codes%3A+the+neural+basis+of+selective+impairment+in+reading+words+and+pseudowords.&rft.au=Xu+B%3BGrafman%2C+J%3BGaillard%2C+W+D%3BIshii%2C+K%3BVega-Bermudez%2C+F%3BPietrini%2C+P%3BReeves-Tyer%2C+P%3BDiCamillo%2C+P%3BTheodore%2C+W&rft.aulast=Xu+B&rft.aufirst=&rft.date=2001-03-01&rft.volume=11&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Cerebral+Cortex&rft.issn=10473211&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia AN - 851461455; 13746830 AB - The gene that encodes nuclear factor (NF-B) essential modulator (or NEMO, also known as IKKg) is required for activation of the transcription factor NF-B. We describe mutations in the puta-tive zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-B a (IB-a) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-B-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor a (TNF-a) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-B activation for B cell immunoglobulin class-switching. JF - Nature Immunology AU - Jain, Ashish AU - Ma, Chi Adrian AU - Liu, Shiyung AU - Brown, Margaret AU - Cohen, Jeffrey AU - Strober, Warren AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 223 EP - 228 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 2 IS - 3 SN - 1529-2908, 1529-2908 KW - Toxicology Abstracts; Immunology Abstracts KW - Missense mutation KW - Dysplasia KW - Lymphocytes B KW - CD40L protein KW - X chromosome KW - Class switching KW - Immunodeficiency KW - Tumor necrosis factor-a KW - Cell activation KW - NF- Kappa B protein KW - Recombination KW - Interleukin 12 KW - Transcription factors KW - NF-B protein KW - Lipopolysaccharides KW - Antigen-presenting cells KW - Tumor necrosis factor- alpha KW - Staphylococcus aureus KW - CD40 antigen KW - Job's syndrome KW - Immunoglobulins KW - X 24370:Natural Toxins KW - F:0695 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/851461455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Immunology&rft.atitle=Specific+missense+mutations+in+NEMO+result+in+hyper-IgM+syndrome+with+hypohydrotic+ectodermal+dysplasia&rft.au=Jain%2C+Ashish%3BMa%2C+Chi+Adrian%3BLiu%2C+Shiyung%3BBrown%2C+Margaret%3BCohen%2C+Jeffrey%3BStrober%2C+Warren&rft.aulast=Jain&rft.aufirst=Ashish&rft.date=2001-03-01&rft.volume=2&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Nature+Immunology&rft.issn=15292908&rft_id=info:doi/10.1038%2F85277 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-02-01 N1 - Last updated - 2013-12-16 N1 - SubjectsTermNotLitGenreText - Missense mutation; Dysplasia; Lymphocytes B; CD40L protein; Class switching; X chromosome; Immunodeficiency; Tumor necrosis factor-a; NF- Kappa B protein; Cell activation; Interleukin 12; Recombination; Transcription factors; NF-B protein; Lipopolysaccharides; Tumor necrosis factor- alpha; Antigen-presenting cells; CD40 antigen; Job's syndrome; Immunoglobulins; Staphylococcus aureus DO - http://dx.doi.org/10.1038/85277 ER - TY - JOUR T1 - Xylanase production by Aspergillus awamori in solid-state fermentation and influence of different nitrogen sources AN - 807289171; 13858967 AB - The use of purified xylan as a substrate for bioconversion into xylanases increases the cost of enzyme production. Consequently, there have been attempts to develop a bioprocess to produce such enzymes using different lignocellulosic residues. Filamentous fungi have been widely used to produce hydrolytic enzymes for industrial applications, including xylanases, whose levels in fungi are generally much higher than those in yeast and bacteria. Considering the industrial importance of xylanases, the present study evaluated the use of milled sugarcane bagasse, without any pretreatment, as a carbon source. Also, the effect of different nitrogen sources and the CN ratio on xylanase production by Aspergillus awamori were investigated, in experiments carried out in solid-state fermentation. High extracellular xylanolytic activity was observed on cultivation of A. awamori on milled sugarcane bagasse and organic nitrogen sources (45 IU/mL for endoxylanase and 3.5 IU/mL for b-xylosidase). Endoxylanase and b-xylosidase activities were higher when sodium nitrate was used as the nitrogen source, when compared with peptone, urea, and ammonium sulfate at the optimized CN ratio of 101. The use of yeast extract as a supplement to the these nitrogen sources resulted in considerable improvementin the production of xylanases, showing the importance of this organic nitrogen source on A. awamori metabolism. JF - Applied Biochemistry and Biotechnology AU - Lemos, Judith LS AU - Fontes, Maria Cde A AU - Pereira, Nei AD - Departamento de Engenharia Bioquimica, Escola de Quimica, Universidade Federal do Rio de Janeiro, Ilha do Fundao, CEP 21949-900, Rio de Janeiro, RJ, Brazil, nei@eq.ufrj.br Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 681 EP - 689 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 91-93 IS - 1-9 SN - 0273-2289, 0273-2289 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - Nitrogen sources KW - Xylan endo-1,3-b-xylosidase KW - Fermentation KW - Fungi KW - Enzymes KW - Urea KW - Carbon sources KW - Xylan endo-1,3- beta -xylosidase KW - Bagasse KW - Ammonium sulfate KW - Industrial applications KW - Xylan KW - peptone KW - bioconversion KW - Aspergillus awamori KW - Metabolism KW - sodium nitrate KW - A 01310:Products of Microorganisms KW - W 30945:Fermentation & Cell Culture KW - K 03320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/807289171?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Biochemistry+and+Biotechnology&rft.atitle=Xylanase+production+by+Aspergillus+awamori+in+solid-state+fermentation+and+influence+of+different+nitrogen+sources&rft.au=Lemos%2C+Judith+LS%3BFontes%2C+Maria+Cde+A%3BPereira%2C+Nei&rft.aulast=Lemos&rft.aufirst=Judith&rft.date=2001-03-01&rft.volume=91-93&rft.issue=1-9&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/10.1385%2FABAB%3A91-93%3A1-9%3A681 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2013-12-04 N1 - SubjectsTermNotLitGenreText - Xylan endo-1,3-b-xylosidase; Nitrogen sources; Fermentation; Fungi; Enzymes; Urea; Carbon sources; Xylan endo-1,3- beta -xylosidase; Bagasse; Industrial applications; Ammonium sulfate; Xylan; peptone; bioconversion; Metabolism; sodium nitrate; Aspergillus awamori DO - http://dx.doi.org/10.1385/ABAB:91-93:1-9:681 ER - TY - JOUR T1 - A factor analysis of the fagerstrom tolerance questionnaire. AN - 77071311; 11316387 AB - A factor analysis of 1309 Fagerstrom Tolerance Questionnaires (FTQ) was performed with LISCOMP software, which utilizes tetrachoric correlations to account for the dichotomous responses of the FTQ. Three factors with eigenvalues greater than 1.0 were obtained, accounting for 56.6% of the variance. Factor 1 was loaded by questions "How soon on waking do you smoke your first cigarette?," "Do you find it difficult to refrain from smoking in places it is forbidden?," "How many cigarettes a day do you smoke?," and "Do you smoke if you are so ill that you are in bed most of the day?" Factor 2 was loaded by questions "Which cigarette would you hate to give up?" and "Do you smoke more during the morning than during the rest of the day?" Factor 3 was loaded exclusively by question "What brand do you smoke?" The question "Do you inhale always, sometimes, or never?" loaded exclusively on a fourth factor, however its eigenvalue did not reach significance. Support is provided for the modification of the eight-item FTQ to the six-item Fagerstrom Test for Nicotine Dependence (FTND). Based on the wording of the questions that loaded on each factor, we propose that Factor 2 assesses the degree of urgency to initiate smoking after overnight abstinence and that Factor 1 reflects the persistence of smoking during waking hours. JF - Addictive behaviors AU - Radzius, A AU - Moolchan, E T AU - Henningfield, J E AU - Heishman, S J AU - Gallo, J J AD - Clinical Pharmacology and Therapeutics Research Branch, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. aradzius@intra.nida.nih.gov PY - 2001 SP - 303 EP - 310 VL - 26 IS - 2 SN - 0306-4603, 0306-4603 KW - Index Medicus KW - Factor Analysis, Statistical KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - Surveys and Questionnaires KW - Tobacco Use Disorder -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77071311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=A+factor+analysis+of+the+fagerstrom+tolerance+questionnaire.&rft.au=Radzius%2C+A%3BMoolchan%2C+E+T%3BHenningfield%2C+J+E%3BHeishman%2C+S+J%3BGallo%2C+J+J&rft.aulast=Radzius&rft.aufirst=A&rft.date=2001-03-01&rft.volume=26&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of drug treatment histories of single and multiple drug abusers in detox. AN - 77069340; 11316384 AB - This study was undertaken to determine differences in previous treatment patterns in individuals currently using different numbers of substances. Medical records of 1198 inpatient detoxification (detox) admissions were analyzed. Numbers of past admissions to completed detox, methadone, or other types of drug abuse treatment were totaled and ranked to determine most frequent type. Within gender, treatment histories of single and multiple drug abusers usually do not differ. The one exception is male multiple drug abusers ages 26-30, who show increased admissions. Possible explanations are that men do not seek treatment before developing medical complications of addiction or until external factors influence admission. There were differences in treatment histories between genders in multiple drug abusers only. Before age 30, women reported increased treatment of certain types. Possible explanations are that treatment priority is given to women who are, or may be, pregnant. Also, younger men may not enter or complete treatment. Previous treatment history may influence many behaviors. The results of this study delineate several valuable indicators for assessing past history. JF - Addictive behaviors AU - Greberman, S B AU - Jasinski, D AD - Division of Intramural Research, National Institutes of Health/National Institute on Drug Ahuse, Baltimore, MD 21224, USA. sgreberm@intra.nida.nih.gov PY - 2001 SP - 285 EP - 288 VL - 26 IS - 2 SN - 0306-4603, 0306-4603 KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Humans KW - Chi-Square Distribution KW - Adult KW - Adolescent KW - Male KW - Female KW - Methadone -- therapeutic use KW - Inactivation, Metabolic KW - Patient Admission -- statistics & numerical data KW - Narcotics -- therapeutic use KW - Mental Health Services -- utilization KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77069340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=Comparison+of+drug+treatment+histories+of+single+and+multiple+drug+abusers+in+detox.&rft.au=Greberman%2C+S+B%3BJasinski%2C+D&rft.aulast=Greberman&rft.aufirst=S&rft.date=2001-03-01&rft.volume=26&rft.issue=2&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Morphometry and estimated bulk oxygen diffusion in larvae of Xenopus laevis under chronic carbon monoxide exposure. AN - 77048864; 11302531 AB - To understand the mechanisms that allow tadpoles of the African clawed frog Xenopus laevis to develop under conditions of impaired convective transport (hemoglobin poisoning with carbon monoxide), whole animal surface area and volume were measured and bulk oxygen diffusion was modeled at four developmental stages (from initiation of heartbeat to pre-metamorphic climax). Surface area [8.5 mm2 at stages Nieuwkoop-Faber (NF) 33-34 to 70.2 mm2 at stages NF 50-51] and volume (1.8 mm3 at stages NF 33-34 to 35.7 mm3 at stages NF 50-51) measured from volumetric analysis from dual plane images of each animal were not significantly different between treatments. Bulk oxygen radial diffusion was estimated by modeling the larvae as a set of adjacent cylinders with different radii. The model was used to predict the oxygen tension at the water-skin interface at which the oxygen tension in the center of the animal is nil (0.7 kPa at stage NF 33-34 and 14.0 kPa at stage NF 50-51), suggesting that bulk oxygen diffusion is sufficient to meet the metabolic demand up to stages NF 46-47 irrespective of the oxygen tension at the water-skin interface. At NF 50-51 an anoxic core in the animal would appear if bulk oxygen diffusion were the only means of oxygen transport at oxygen tensions below 15 kPa. However, the relative volume of the anoxic core would only exceed 10% of the total volume of the animal only at oxygen tensions below 5 kPa. Therefore, the ten-fold increase in mass between NF 50-51 and metamorphosis would prove insufficient for embryonic oxygen requirements via simple diffusion, and therefore would require additional transport mechanisms. JF - Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology AU - Territo, P R AU - Altimiras, J AD - Department of Biological Sciences, University of Nevada, Las Vegas 89154-4004, USA. territop@zeus.nhlbi.nih.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 145 EP - 153 VL - 171 IS - 2 SN - 0174-1578, 0174-1578 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Larva -- physiology KW - Linear Models KW - Body Surface Area KW - Diffusion KW - Body Constitution KW - Female KW - Oxygen -- pharmacokinetics KW - Xenopus laevis -- growth & development KW - Models, Biological KW - Carbon Monoxide -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77048864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+comparative+physiology.+B%2C+Biochemical%2C+systemic%2C+and+environmental+physiology&rft.atitle=Morphometry+and+estimated+bulk+oxygen+diffusion+in+larvae+of+Xenopus+laevis+under+chronic+carbon+monoxide+exposure.&rft.au=Territo%2C+P+R%3BAltimiras%2C+J&rft.aulast=Territo&rft.aufirst=P&rft.date=2001-03-01&rft.volume=171&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Journal+of+comparative+physiology.+B%2C+Biochemical%2C+systemic%2C+and+environmental+physiology&rft.issn=01741578&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV postexposure prophylaxis in the 21st century. AN - 77046210; 11294718 AB - The administration of postexposure prophylaxis has become the standard of care for occupational exposures to HIV. We have learned a great deal about the safety and potential efficacy of these agents, as well as the optimal management of health-care workers occupationally exposed to HIV. This article describes the current state of knowledge in this field, identifies substantive questions to be answered, and summarizes basic principles of postexposure management. JF - Emerging infectious diseases AU - Henderson, D K AD - Warren G. Magnuson Clinical Center, Bethesda, Maryland, USA. dkh.nih.gov PY - 2001 SP - 254 EP - 258 VL - 7 IS - 2 SN - 1080-6040, 1080-6040 KW - Anti-HIV Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Occupational Exposure -- prevention & control KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- prevention & control KW - HIV Infections -- drug therapy KW - Health Personnel KW - Infectious Disease Transmission, Patient-to-Professional -- prevention & control KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77046210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+infectious+diseases&rft.atitle=HIV+postexposure+prophylaxis+in+the+21st+century.&rft.au=Henderson%2C+D+K&rft.aulast=Henderson&rft.aufirst=D&rft.date=2001-03-01&rft.volume=7&rft.issue=2&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=Emerging+infectious+diseases&rft.issn=10806040&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peripheral neuropathy and antiretroviral drugs. AN - 77041808; 11293802 AB - Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders. JF - Journal of the peripheral nervous system : JPNS AU - Dalakas, M C AD - Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1382, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 14 EP - 20 VL - 6 IS - 1 SN - 1085-9489, 1085-9489 KW - Index Medicus KW - Humans KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - Acquired Immunodeficiency Syndrome -- complications KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Peripheral Nervous System Diseases -- virology KW - Peripheral Nervous System Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77041808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+peripheral+nervous+system+%3A+JPNS&rft.atitle=Peripheral+neuropathy+and+antiretroviral+drugs.&rft.au=Dalakas%2C+M+C&rft.aulast=Dalakas&rft.aufirst=M&rft.date=2001-03-01&rft.volume=6&rft.issue=1&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+peripheral+nervous+system+%3A+JPNS&rft.issn=10859489&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - NIH symposium summary: organ preservation therapies for squamous cancers of the head and neck. AN - 77041744; 11297272 AB - This symposium, sponsored by the NIH Office of Rare Diseases, the National Cancer Institute, the National Institute of Deafness and Other Communication Disorders, and the National Institute of Dental and Craniofacial Diseases, reviewed the current status of organ preservation therapies for head and neck cancers, as well as promising newer approaches for therapy and for toxicity amelioration. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Conley, B A AU - Cumberlin, R AU - Sandberg, A AU - Solomon, B AU - Van Waes, C Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 745 EP - 753 VL - 7 IS - 3 KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Clinical Trials as Topic KW - Head and Neck Neoplasms -- therapy KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77041744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=NIH+symposium+summary%3A+organ+preservation+therapies+for+squamous+cancers+of+the+head+and+neck.&rft.au=Conley%2C+B+A%3BCumberlin%2C+R%3BSandberg%2C+A%3BSolomon%2C+B%3BVan+Waes%2C+C&rft.aulast=Conley&rft.aufirst=B&rft.date=2001-03-01&rft.volume=7&rft.issue=3&rft.spage=745&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Screening for and identification of novel agents directed at renal cell carcinoma. AN - 77038814; 11297258 AB - We were interested in identifying novel agents for renal cell carcinoma (RCC) by screening for activities that model renal tumor biology. Searching for relative renal cell sensitivity and leukemia insensitivity among cytotoxicity profiles in the NCI Drug Screen database, we identified 16 potential agents with renal selectivity. We evaluated the agents in 10 RCC cell lines (of primary and metastatic origin) isolated from 5 patients. The 50% inhibitory concentrations (IC50) in these cell lines ranged from 0.019 +/- 0.013 to 11.4 +/- 0.55 microM and were comparable with values obtained with renal cell lines in the NCI Drug Screen panel. Because RCC are slowly growing tumors, we evaluated the compounds on rapidly (27% S phase) or slowly (6% S phase) growing cells. In contrast to doxorubicin, where cytotoxicity was restricted to rapidly proliferating cells, three compounds (NSC 280074, 281613, and 281817) were more cytotoxic in slowly proliferating cells. NSC 72151 and 268965 were equitoxic for both populations. NSC 94889, 638850, and 630938 were more cytotoxic in rapidly growing cells. In in vitro time exposure studies, four compounds, NSC 268965, 280074, 281613, and 281817, were maximally cytotoxic with as little as 3 h exposure time. From an analysis comparing the p53 genotype of the 60 cell lines of the National Cancer Institute (NCI) Drug Screen with the cytotoxicity profiles for the 16 putative renal compounds, 13 compounds were classified as likely to be indifferent to p53 status. We also developed a panel specificity detection method for the NCI Drug Screen database to evaluate the prevalence of renal sensitive compounds. Of the 16 studied compounds, 14 were among those identified as renal sensitive by the statistical analysis. Lastly, we found reduced tumor growth in mice with established renal human tumor xenografts after treatment with two of the renal active compounds. These studies describe compounds with potential renal activity that are candidates for preclinical development for renal cell carcinoma. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Mertins, S D AU - Myers, T G AU - Hollingshead, M AU - Dykes, D AU - Bodde, E AU - Tsai, P AU - Jefferis, C A AU - Gupta, R AU - Linehan, W M AU - Alley, M AU - Bates, S E AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. smertins@box-s.nih.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 620 EP - 633 VL - 7 IS - 3 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - P-Glycoprotein KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Neoplasm Transplantation KW - Genotype KW - Leukemia -- drug therapy KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - P-Glycoprotein -- metabolism KW - Genes, p53 -- genetics KW - Models, Chemical KW - Inhibitory Concentration 50 KW - Maximum Tolerated Dose KW - Time Factors KW - Cell Cycle -- drug effects KW - Bromodeoxyuridine -- metabolism KW - Cell Division KW - Kidney Neoplasms -- drug therapy KW - Carcinoma, Renal Cell -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Drug Design KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77038814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Screening+for+and+identification+of+novel+agents+directed+at+renal+cell+carcinoma.&rft.au=Mertins%2C+S+D%3BMyers%2C+T+G%3BHollingshead%2C+M%3BDykes%2C+D%3BBodde%2C+E%3BTsai%2C+P%3BJefferis%2C+C+A%3BGupta%2C+R%3BLinehan%2C+W+M%3BAlley%2C+M%3BBates%2C+S+E&rft.aulast=Mertins&rft.aufirst=S&rft.date=2001-03-01&rft.volume=7&rft.issue=3&rft.spage=620&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 gene expression in relation to indoor exposure to unvented coal smoke in Xuan Wei, China. AN - 77020697; 11285870 AB - Lung cancer mortality rates in Xuan Wei County, which are among the highest in China, have previously been associated with exposure to indoor emissions from burning smoky coal. To determine if this association is stronger among lung cancer patients with abnormal expression of p53, we performed a population-based case-control study. Ninety-seven newly diagnosed lung cancer patients and 97 controls, individually matched by age, sex, and home fuel type, were enrolled. We used immunocytochemical methods to assess p53 protein accumulation in exfoliated tumor cells isolated from sputum samples. As expected, the amount of lifetime smoky coal use was associated with an overall increase in lung cancer risk. Compared with subjects who used less than 130 tons of smoky coal during their lifetime, the odds ratios (OR) for lung cancer were 1.48 (95% confidence interval [CI], 0.73 to 3.02) for subjects exposed to 130 to 240 tons, and 3.21 (95% CI, 1.23 to 9.03) for subjects who used more than 240 tons of smoky coal (P for trend 0.01). The effect was due almost exclusively to the pattern in women, almost all of whom were nonsmokers. Further, among highly exposed women, the association was substantially larger and achieved statistical significance only among patients with sputum samples that were positive for p53 overexpression (OR, 18.72; 95% CI, 1.77 to 383.38 vs OR, 4.80; 95% CI, 0.66 to 43.87 for p53-negative cases). This study suggests that exposure to the combustion products of smoky coal in Xuan Wei is more strongly associated with women who have lung cancer accompanied by p53 protein overexpression in exfoliated tumor cells. JF - Journal of occupational and environmental medicine AU - Lan, Q AU - Feng, Z AU - Tian, D AU - He, X AU - Rothman, N AU - Tian, L AU - Lu, X AU - Terry, M B AU - Mumford, J L AD - University of North Carolina, Chapl Hill, USA. qingl@mail.nih.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 226 EP - 230 VL - 43 IS - 3 SN - 1076-2752, 1076-2752 KW - Coal KW - 0 KW - Smoke KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Risk Factors KW - Humans KW - China -- epidemiology KW - Case-Control Studies KW - Middle Aged KW - Sputum KW - Male KW - Female KW - Air Pollution, Indoor -- adverse effects KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Genes, p53 KW - Lung Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77020697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+and+environmental+medicine&rft.atitle=p53+gene+expression+in+relation+to+indoor+exposure+to+unvented+coal+smoke+in+Xuan+Wei%2C+China.&rft.au=Lan%2C+Q%3BFeng%2C+Z%3BTian%2C+D%3BHe%2C+X%3BRothman%2C+N%3BTian%2C+L%3BLu%2C+X%3BTerry%2C+M+B%3BMumford%2C+J+L&rft.aulast=Lan&rft.aufirst=Q&rft.date=2001-03-01&rft.volume=43&rft.issue=3&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+and+environmental+medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevation of breast carcinoma Nm23-H1 metastasis suppressor gene expression and reduced motility by DNA methylation inhibition. AN - 77013275; 11280805 AB - We hypothesize that elevation of Nm23-H1 expression in micrometastatic breast cancer cells may inhibit their metastatic colonization and further invasion, and induce differentiation, thus resulting in a clinical benefit. The current study investigated the possible contribution of DNA methylation to the regulation of Nm23-H1 expression, based on the observation that two CpG islands are present in its promoter. 5-Aza-2'-deoxycytidine (5-Aza-CdR), a DNA methylation inhibitor, increased the Nm23-H1 expression of 5 of 11 human breast carcinoma cell lines in vitro, including 3 of 3 metastatically competent lines. Increased Nm23-H1 expression was accompanied by a reduction in motility in vitro, with minimal effect on proliferation. Both increased Nm23-H1 expression and decreased motility were observed using low (75 nM) concentrations of 5-Aza-CdR. Array analysis of MDA-MB-231 breast carcinoma cells treated with 5-Aza-CdR confirmed the elevation of nm23-H1 mRNA, whereas relatively few other genes exhibited altered expression. Bisulfite sequencing of the two CpG islands in a panel of cell lines and in 20 infiltrating ductal carcinomas revealed that one island (-3090 bp to -3922 bp) exhibited infrequent differential methylation. The data indicate that DNA methylation inhibitors can directly or indirectly cause both elevation of Nm23-H1 expression and decreased function in one aspect of metastasis, motility. JF - Cancer research AU - Hartsough, M T AU - Clare, S E AU - Mair, M AU - Elkahloun, A G AU - Sgroi, D AU - Osborne, C K AU - Clark, G AU - Steeg, P S AD - Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. hartso@box-h.nih.gov Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 2320 EP - 2327 VL - 61 IS - 5 SN - 0008-5472, 0008-5472 KW - Antimetabolites, Antineoplastic KW - 0 KW - NM23 Nucleoside Diphosphate Kinases KW - Transcription Factors KW - decitabine KW - 776B62CQ27 KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Neoplasm Metastasis KW - CpG Islands -- genetics KW - Promoter Regions, Genetic -- genetics KW - Antimetabolites, Antineoplastic -- pharmacology KW - Breast Neoplasms -- genetics KW - Azacitidine -- pharmacology KW - Carcinoma, Ductal, Breast -- pathology KW - Genes, Tumor Suppressor KW - Azacitidine -- analogs & derivatives KW - Gene Expression Regulation, Neoplastic -- physiology KW - Breast Neoplasms -- metabolism KW - Cell Movement -- genetics KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Monomeric GTP-Binding Proteins -- genetics KW - Monomeric GTP-Binding Proteins -- biosynthesis KW - Breast Neoplasms -- pathology KW - Carcinoma, Ductal, Breast -- metabolism KW - DNA Methylation -- drug effects KW - Carcinoma, Ductal, Breast -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77013275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Elevation+of+breast+carcinoma+Nm23-H1+metastasis+suppressor+gene+expression+and+reduced+motility+by+DNA+methylation+inhibition.&rft.au=Hartsough%2C+M+T%3BClare%2C+S+E%3BMair%2C+M%3BElkahloun%2C+A+G%3BSgroi%2C+D%3BOsborne%2C+C+K%3BClark%2C+G%3BSteeg%2C+P+S&rft.aulast=Hartsough&rft.aufirst=M&rft.date=2001-03-01&rft.volume=61&rft.issue=5&rft.spage=2320&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of beta-catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade. AN - 77012877; 11280770 AB - Mutations affecting phosphorylation sites in the beta-catenin gene have been implicated in the development of human and rodent hepatocellular carcinomas (HCCs). To further investigate the involvement of this gene in hepatocarcinogenesis, we used several transgenic mouse models of hepatic tumors induced by overexpression of c-myc in the liver either alone or in combination with transforming growth factor (TGF) alpha or TGF-beta1. Activation of beta-catenin, as judged by the presence of mutations and/or nuclear translocation of the protein, was most frequent in liver tumors from c-myc (4/17; 23.5%) and c-myc/TGF-beta1 (6/18; 33.3%) transgenic mice. However, it was very rare in faster growing and histologically more aggressive HCCs developed in c-myc/TGF-alpha mice (1/20; 5%). Administration of diethylnitrosamine, phenobarbital, or 2-amino-3,8-diethylimidazo[4,5-f]quinoxaline did not significantly affect the occurrence of beta-catenin mutations. Notably, nuclear accumulation of beta-catenin was observed only in adenomas and highly differentiated carcinomas with eosinophilic phenotype. Furthermore, preneoplastic lesions with eosinophilic phenotype frequently displayed focal nuclear positivity, colocalized with areas of high proliferation. In contrast, basophilic and clear-cell foci, as well as pseudo-glandular and poorly differentiated HCCs, exhibited a normal or reduced membranous immunoreactivity for beta-catenin. These studies suggest that nuclear translocation of beta-catenin and activation of Wingless/Wnt signaling may represent an early event in liver carcinogenesis, providing a growth advantage in a subset of hepatic tumors with a more differentiated phenotype. JF - Cancer research AU - Calvisi, D F AU - Factor, V M AU - Loi, R AU - Thorgeirsson, S S AD - Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 2085 EP - 2091 VL - 61 IS - 5 SN - 0008-5472, 0008-5472 KW - CTNNB1 protein, human KW - 0 KW - CTNNB1 protein, mouse KW - Cytoskeletal Proteins KW - Proto-Oncogene Proteins c-myc KW - Trans-Activators KW - Transforming Growth Factor alpha KW - beta Catenin KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Phenotype KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Mice, Inbred CBA KW - Tumor Cells, Cultured KW - Transforming Growth Factor alpha -- genetics KW - Phosphorylation KW - Transforming Growth Factor alpha -- biosynthesis KW - Mice, Inbred C57BL KW - Genes, myc -- genetics KW - Immunohistochemistry KW - Gene Expression Regulation, Neoplastic KW - Liver Neoplasms, Experimental -- genetics KW - Cytoskeletal Proteins -- biosynthesis KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- metabolism KW - Cytoskeletal Proteins -- metabolism KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77012877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Activation+of+beta-catenin+during+hepatocarcinogenesis+in+transgenic+mouse+models%3A+relationship+to+phenotype+and+tumor+grade.&rft.au=Calvisi%2C+D+F%3BFactor%2C+V+M%3BLoi%2C+R%3BThorgeirsson%2C+S+S&rft.aulast=Calvisi&rft.aufirst=D&rft.date=2001-03-01&rft.volume=61&rft.issue=5&rft.spage=2085&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A prospective, randomized, double-blind, placebo-controlled trial evaluating the effect of nystatin on the development of oral irritation in patients receiving high-dose intravenous interleukin-2. AN - 76996448; 11265777 AB - Interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and renal cell cancer for nearly two decades, and much progress has been made in ameliorating its adverse effects. One bothersome adverse effect, oral pain or oral irritation, is usually treated with an oral antifungal antibiotic, nystatin. The authors performed a prospective, randomized, double-blind, placebo-controlled trial involving 64 patients to evaluate the effect of prophylactic administration of nystatin or placebo on the development of oral irritation in patients receiving high-dose intravenous IL-2. No difference was found between patients randomized to receive nystatin or placebo in their rates of development of oral irritation, the severity of IL-2 adverse effects, the duration of their treatment, the rate of development of positive studies for oral yeast, or their pattern of experiencing other adverse effects. Thus, patients who receive high-dose intravenous IL-2 should not be treated prophylactically with nystatin to prevent oral irritation, and clinicians should seek evidence of the presence of oral thrush before using antifungal agents to treat oral pain in these patients. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Ohnmacht, G A AU - Phan, G Q AU - Mavroukakis, S A AU - Steinberg, S M AU - Shea, Y R AU - Witebsky, F G AU - McIntyre, L S AU - Goodwin, R S AU - Muehlbauer, P M AU - Morton, K E AU - Rogers-Freezer, L J AU - Seipp, C A AU - Rosenberg, S A AU - Marincola, F M AD - Surgery Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892-1502, USA. PY - 2001 SP - 188 EP - 192 VL - 24 IS - 2 SN - 1524-9557, 1524-9557 KW - Antifungal Agents KW - 0 KW - Interleukin-2 KW - Placebos KW - Nystatin KW - 1400-61-9 KW - Index Medicus KW - Kidney Neoplasms -- drug therapy KW - Prospective Studies KW - Double-Blind Method KW - Candidiasis, Oral -- drug therapy KW - Humans KW - Melanoma -- drug therapy KW - Adult KW - Aged KW - Middle Aged KW - Carcinoma, Renal Cell -- drug therapy KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Mouth Diseases -- chemically induced KW - Nystatin -- therapeutic use KW - Mouth Diseases -- prevention & control KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76996448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=A+prospective%2C+randomized%2C+double-blind%2C+placebo-controlled+trial+evaluating+the+effect+of+nystatin+on+the+development+of+oral+irritation+in+patients+receiving+high-dose+intravenous+interleukin-2.&rft.au=Ohnmacht%2C+G+A%3BPhan%2C+G+Q%3BMavroukakis%2C+S+A%3BSteinberg%2C+S+M%3BShea%2C+Y+R%3BWitebsky%2C+F+G%3BMcIntyre%2C+L+S%3BGoodwin%2C+R+S%3BMuehlbauer%2C+P+M%3BMorton%2C+K+E%3BRogers-Freezer%2C+L+J%3BSeipp%2C+C+A%3BRosenberg%2C+S+A%3BMarincola%2C+F+M&rft.aulast=Ohnmacht&rft.aufirst=G&rft.date=2001-03-01&rft.volume=24&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Recombinant immunotoxin for cancer therapy: current status and prospective]. AN - 76995213; 11268658 JF - Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme AU - Nagata, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institute of Health, USA. nagatas@pop.nci.nih.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 540 EP - 546 VL - 46 IS - 4 Suppl SN - 0039-9450, 0039-9450 KW - Antibodies, Neoplasm KW - 0 KW - Immunotoxins KW - Ligands KW - Recombinant Proteins KW - Toxins, Biological KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Recombinant Proteins -- adverse effects KW - Clinical Trials as Topic KW - Drug Design KW - Recombinant Proteins -- therapeutic use KW - Neoplasms -- pathology KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Neoplasms -- therapy KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76995213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tanpakushitsu+kakusan+koso.+Protein%2C+nucleic+acid%2C+enzyme&rft.atitle=%5BRecombinant+immunotoxin+for+cancer+therapy%3A+current+status+and+prospective%5D.&rft.au=Nagata%2C+S&rft.aulast=Nagata&rft.aufirst=S&rft.date=2001-03-01&rft.volume=46&rft.issue=4+Suppl&rft.spage=540&rft.isbn=&rft.btitle=&rft.title=Tanpakushitsu+kakusan+koso.+Protein%2C+nucleic+acid%2C+enzyme&rft.issn=00399450&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenylacetate pharmacokinetics based on iterative two-stage population analysis. AN - 76971830; 11253852 AB - To determine the population pharmacokinetics of phenylacetate using iterative two-stage analysis implemented with ADAPT 11 software. United States government research hospital. Retrospective pharmacokinetic analysis. Sixty-seven patients with refractory solid tumors. Subjects received from 1-10 courses/individual (total 141 courses) of therapy with either twice-daily administration or continuous infusions of phenylacetate. Extensive plasma concentration measurements were performed after the initial dose or start of infusion, with sparse sampling during subsequent courses of therapy. Phenylacetate plasma concentration-time profiles were described by a one-compartment, capacity-limited clearance model with incorporation of parameters to describe extent of induction of clearance and the rate of induction. Median estimates for volume of distribution, maximum rate of drug elimination, Michaelis-Menten constant, and induction factor, and rate of onset of induction of drug clearance were 0.33 (0.26, 0.48) L/kg, 21.8 (16.3, 28.0) mg/kg/hour, 94.6 (48.8, 153.0) mg/L, 1.28 (1.06, 1.66), and 0.0038 (0.0019, 0.0058) hour(-1), respectively. The results of this study are similar to previous pharmacokinetic evaluations using the Abbottbase PKS system but suggest that earlier analyses were suboptimal. JF - Pharmacotherapy AU - Burstein, A H AU - Reed, E AU - Tompkins, A C AU - Venzon, D AU - Figg, W D AD - Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 281 EP - 286 VL - 21 IS - 3 SN - 0277-0008, 0277-0008 KW - Antimetabolites, Antineoplastic KW - 0 KW - Phenylacetates KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Spectrophotometry, Ultraviolet KW - Sampling Studies KW - Retrospective Studies KW - Population KW - Middle Aged KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Phenylacetates -- administration & dosage KW - Phenylacetates -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Phenylacetates -- blood KW - Antimetabolites, Antineoplastic -- blood KW - Antimetabolites, Antineoplastic -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76971830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Phenylacetate+pharmacokinetics+based+on+iterative+two-stage+population+analysis.&rft.au=Burstein%2C+A+H%3BReed%2C+E%3BTompkins%2C+A+C%3BVenzon%2C+D%3BFigg%2C+W+D&rft.aulast=Burstein&rft.aufirst=A&rft.date=2001-03-01&rft.volume=21&rft.issue=3&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction: reviews of environmental health, 2001. AN - 76969853; 11250800 JF - Environmental health perspectives AU - Goehl, T J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 3 EP - 4 VL - 109 Suppl 1 SN - 0091-6765, 0091-6765 KW - Xenobiotics KW - 0 KW - Index Medicus KW - Public Health KW - International Cooperation KW - Humans KW - Xenobiotics -- toxicity KW - Environmental Health KW - Endocrine System -- drug effects KW - Biomedical Technology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76969853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Introduction%3A+reviews+of+environmental+health%2C+2001.&rft.au=Goehl%2C+T+J&rft.aulast=Goehl&rft.aufirst=T&rft.date=2001-03-01&rft.volume=109+Suppl+1&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-03-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 2001 Mar;109 Suppl 1:5-20 [11250801] Environ Health Perspect. 1999 Oct;107(10):773-8 [10504141] Environ Health Perspect. 2001 Mar;109 Suppl 1:27-34 [11250803] Environ Health Perspect. 2001 Mar;109 Suppl 1:35-47 [11250804] Environ Health Perspect. 2001 Mar;109 Suppl 1:49-68 [11250805] Environ Health Perspect. 2001 Mar;109 Suppl 1:69-75 [11250806] Environ Health Perspect. 2001 Mar;109 Suppl 1:77-8 [11250807] Environ Health Perspect. 2001 Mar;109 Suppl 1:79-91 [11250808] Environ Health Perspect. 2001 Mar;109 Suppl 1:93-100 [11250809] Environ Health Perspect. 2001 Mar;109 Suppl 1:101-11 [11250810] Environ Health Perspect. 2001 Mar;109 Suppl 1:113-39 [11250811] Environ Health Perspect. 2001 Mar;109 Suppl 1:141-61 [11250812] Environ Health Perspect. 2001 Mar;109 Suppl 1:163-8 [11250813] Environ Health Perspect. 1998 Apr;106(4):A168-9 [9625615] Environ Health Perspect. 2001 Mar;109 Suppl 1:21-6 [11250802] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gastrointestinal cells of IL-7 receptor null mice exhibit increased sensitivity to irradiation. AN - 76967594; 11207240 AB - IL-7 is a critical cytokine in the development of T and B cells but little is known about its activity on nonhematopoietic cells. An unexpected finding was noted in allogeneic bone marrow transplant studies using IL-7 receptor null (IL-7R alpha(-/-)) mice as recipients. These mice exhibited a significantly greater weight loss after total body irradiation compared with wild type, IL-7R alpha(+/+), mice. Pathological assessment indicated greater intestinal crypt damage in IL-7R alpha(-/-) recipients, suggesting these mice may be predisposed to gut destruction. Therefore, we determined the effect of the conditioning itself on the intestinal tract of these mice. IL-7R alpha(-/-) mice and IL-7R alpha(+/+) mice were irradiated and examined for lesions and apoptosis within the small intestine. In moribund animals, IL-7R alpha(-/-) mice had extensive damage in the small intestine, including marked ablation of the crypts and extreme shortening of villi following 1500 cGy total body irradiation. In contrast, by 8 days after irradiation, the small intestines of IL-7R alpha(+/+) mice had regenerated as distinguished by normal villus length and hyperplastic crypts. Following 750 cGy irradiation, IL-7R alpha(-/-) mice had a higher proportion of apoptotic cells in the crypts and an accompanying increase in the pro-apoptotic protein Bak was expressed in intestinal epithelial cells. These results demonstrate the increased radiosensitivity of intestinal stem cells within the crypts in IL-7R alpha(-/-) mice and a role for IL-7 in the protection of radiation-induced apoptosis in these same cells. This study describes a novel role of IL-7 in nonhematopoietic tissues. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Welniak, L A AU - Khaled, A R AU - Anver, M R AU - Komschlies, K L AU - Wiltrout, R H AU - Durum, S AU - Ruscetti, F R AU - Blazar, B R AU - Murphy, W J AD - Laboratory of Leukocyte Biology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 2924 EP - 2928 VL - 166 IS - 5 SN - 0022-1767, 0022-1767 KW - Bak1 protein, mouse KW - 0 KW - Bcl2l1 protein, mouse KW - Membrane Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Receptors, Interleukin-7 KW - bcl-2 Homologous Antagonist-Killer Protein KW - bcl-X Protein KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Proto-Oncogene Proteins c-bcl-2 -- radiation effects KW - Weight Loss -- immunology KW - Weight Loss -- genetics KW - Membrane Proteins -- genetics KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Bone Marrow Transplantation -- immunology KW - Apoptosis -- genetics KW - Whole-Body Irradiation KW - Graft vs Host Disease -- pathology KW - Membrane Proteins -- biosynthesis KW - Graft vs Host Disease -- genetics KW - Membrane Proteins -- radiation effects KW - Weight Loss -- radiation effects KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Graft vs Host Disease -- immunology KW - Apoptosis -- radiation effects KW - Apoptosis -- immunology KW - Mice KW - Dose-Response Relationship, Radiation KW - Transplantation, Homologous KW - Bone Marrow Transplantation -- pathology KW - Dose-Response Relationship, Immunologic KW - Mice, Inbred C57BL KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Female KW - Receptors, Interleukin-7 -- deficiency KW - Intestinal Mucosa -- radiation effects KW - Receptors, Interleukin-7 -- biosynthesis KW - Intestinal Mucosa -- immunology KW - Gamma Rays KW - Intestine, Small -- metabolism KW - Receptors, Interleukin-7 -- genetics KW - Intestinal Mucosa -- pathology KW - Intestinal Mucosa -- metabolism KW - Intestine, Small -- pathology KW - Intestine, Small -- immunology KW - Intestine, Small -- radiation effects KW - Receptors, Interleukin-7 -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76967594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Gastrointestinal+cells+of+IL-7+receptor+null+mice+exhibit+increased+sensitivity+to+irradiation.&rft.au=Welniak%2C+L+A%3BKhaled%2C+A+R%3BAnver%2C+M+R%3BKomschlies%2C+K+L%3BWiltrout%2C+R+H%3BDurum%2C+S%3BRuscetti%2C+F+R%3BBlazar%2C+B+R%3BMurphy%2C+W+J&rft.aulast=Welniak&rft.aufirst=L&rft.date=2001-03-01&rft.volume=166&rft.issue=5&rft.spage=2924&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Random mutagenesis-PCR to introduce alterations into defined DNA sequences for validation of SNP and mutation detection methods. AN - 76957954; 11241843 AB - Sensitive and high throughput techniques are required for the detection of DNA sequence variants such as single nucleotide polymorphisms (SNPs) and mutations. One problem, common to all methods of SNP and mutation detection, is that experimental conditions required for detection of DNA sequence variants depend on the specific DNA sequence to be analyzed. Although algorithms and other calculations have been developed to predict the experimental conditions required to detect DNA sequence variation in a specific DNA sequence, these algorithms do not always provide reliable information and experimental conditions for SNP and mutation detection must be devised empirically. Determination of experimental conditions for detection of DNA sequence variation is difficult when samples containing only wild type sequence are available. When patient derived positive controls are used, increasingly there are valid concerns about commercial ownership and patient privacy. This report presents a rapid and efficient method, employing random mutagenesis-PCR (RM-PCR) using low fidelity DNA polymerase, to randomly introduce single and multiple base substitutions and deletions into DNA sequences of interest. Clones with sequence changes were used to validate denaturing HPLC (DHPLC) algorithm predictions, optimize conditions for mutation detection in exon 15 of the tyrosine kinase domain of the MET proto-oncogene, and to confirm the association between specific DNA sequence changes and unique DHPLC chromatographic profiles (signatures). Finally, DNA from 33 papillary renal carcinoma (PRC) patients was screened for mutations in exon 15 of MET using "validated" DHPLC conditions as a proof of principle application of RM-PCR. Use of RM-PCR for DHPLC and other SNP/mutation detection methods is discussed along with challenges associated with detecting sequence alterations in mixed tumor/normal tissue, pooled samples, and from regions of the genome that have been amplified during tumorigenesis or duplicated during evolution. Hum Mutat 17:210-219, 2001. Published 2001 Wiley-Liss, Inc. JF - Human mutation AU - Nickerson, M L AU - Warren, M B AU - Zbar, B AU - Schmidt, L S AD - Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, USA. nickersm@mail.ncifcrf.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 210 EP - 219 VL - 17 IS - 3 KW - DNA KW - 9007-49-2 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - Exons -- genetics KW - Proto-Oncogene Proteins c-met -- genetics KW - Humans KW - Polymerase Chain Reaction -- methods KW - DNA -- genetics KW - Chromatography, High Pressure Liquid -- methods KW - DNA -- chemistry KW - Sequence Analysis, DNA KW - Mutation KW - Mutagenesis KW - Cloning, Molecular KW - DNA Mutational Analysis -- methods KW - Polymorphism, Single Nucleotide -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76957954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+mutation&rft.atitle=Random+mutagenesis-PCR+to+introduce+alterations+into+defined+DNA+sequences+for+validation+of+SNP+and+mutation+detection+methods.&rft.au=Nickerson%2C+M+L%3BWarren%2C+M+B%3BZbar%2C+B%3BSchmidt%2C+L+S&rft.aulast=Nickerson&rft.aufirst=M&rft.date=2001-03-01&rft.volume=17&rft.issue=3&rft.spage=210&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy. AN - 71011845; 11442150 AB - Perimenstrual catamenial epilepsy may in part be due to withdrawal of the endogenous progesterone-derived neurosteroid allopregnanolone that potentiates gamma-aminobutyric acidA (GABA(A)) receptor-mediated inhibition. Here we sought to determine whether the anticonvulsant potencies of neuroactive steroids, benzodiazepines, phenobarbital (PB), and valproate (VPA) are altered during the heightened seizure susceptibility accompanying neurosteroid withdrawal in a rat model of perimenstrual catamenial epilepsy. Test drugs were evaluated for their ability to alter the convulsant activity of pentylenetetrazol (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure to high levels of progesterone (and its neurosteroid metabolites), and in pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment with the 5alpha-reductase inhibitor finasteride. Test drugs were administered at doses equivalent to twice their ED50 values for protection against PTZ-induced clonic seizures in naive young adult female rats. The anticonvulsant activity of allopregnanolone (5 mg/kg, s.c.), pregnanolone (5 mg/kg, s.c.), allotetrahydrodeoxycorticosterone (15 mg/kg, s.c.), and tetrahydrodeoxycorticosterone (10 mg/kg, s.c.) were enhanced by 34-127% after neurosteroid withdrawal. The anticonvulsant activity of PB (65 mg/kg, i.p.) was also enhanced by 24% in neurosteroid-withdrawn animals. In contrast, the anticonvulsant activity of diazepam (4 mg/kg, i.p.), bretazenil (0.106 mg/kg, i.p.), and VPA (560 mg/kg, i.p.) were reduced or unchanged in neurosteroid-withdrawn animals. The anticonvulsant activity of neuroactive steroids is potentiated after neurosteroid withdrawal, supporting the use of such agents in the treatment of perimenstrual catamenial epilepsy. JF - Epilepsia AU - Reddy, D S AU - Rogawski, M A AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1408, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 337 EP - 344 VL - 42 IS - 3 SN - 0013-9580, 0013-9580 KW - Anticonvulsants KW - 0 KW - Benzodiazepinones KW - Receptors, GABA KW - Steroids KW - Desoxycorticosterone KW - 40GP35YQ49 KW - tetrahydrodeoxycorticosterone KW - 4AB717DP4A KW - Valproic Acid KW - 614OI1Z5WI KW - Pregnanolone KW - BXO86P3XXW KW - bretazenil KW - OSZ0E9DGOJ KW - Diazepam KW - Q3JTX2Q7TU KW - Pentylenetetrazole KW - WM5Z385K7T KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Benzodiazepinones -- therapeutic use KW - Receptors, GABA -- drug effects KW - Animals KW - Allosteric Regulation -- drug effects KW - Pentylenetetrazole -- pharmacology KW - Dose-Response Relationship, Drug KW - Diazepam -- pharmacology KW - Pseudopregnancy -- blood KW - Valproic Acid -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Diazepam -- therapeutic use KW - Phenobarbital -- pharmacology KW - Receptors, GABA -- physiology KW - Valproic Acid -- therapeutic use KW - Benzodiazepinones -- pharmacology KW - Phenobarbital -- therapeutic use KW - Female KW - Steroids -- therapeutic use KW - Menstrual Cycle -- physiology KW - Substance Withdrawal Syndrome -- prevention & control KW - Pregnanolone -- blood KW - Steroids -- pharmacology KW - Disease Models, Animal KW - Pregnanolone -- pharmacology KW - Epilepsy -- drug therapy KW - Anticonvulsants -- therapeutic use KW - Anticonvulsants -- blood KW - Desoxycorticosterone -- analogs & derivatives KW - Anticonvulsants -- pharmacology KW - Epilepsy -- chemically induced KW - Steroids -- blood KW - Epilepsy -- prevention & control KW - Pregnanolone -- therapeutic use KW - Desoxycorticosterone -- pharmacology KW - Substance Withdrawal Syndrome -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71011845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Enhanced+anticonvulsant+activity+of+neuroactive+steroids+in+a+rat+model+of+catamenial+epilepsy.&rft.au=Reddy%2C+D+S%3BRogawski%2C+M+A&rft.aulast=Reddy&rft.aufirst=D&rft.date=2001-03-01&rft.volume=42&rft.issue=3&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurosteroid withdrawal model of perimenstrual catamenial epilepsy. AN - 70984966; 11442149 AB - Perimenstrual catamenial epilepsy, the increase in seizure frequency that some women with epilepsy experience near the time of menstruation, may in part be related to withdrawal of the progesterone metabolite allopregnanolone, an endogenous anticonvulsant neurosteroid that is a potent positive allosteric gamma-aminobutyric acidA (GABA(A)) receptor modulator. The objective of this study was to develop an animal model of perimenstrual catamenial epilepsy for use in evaluating drug-treatment strategies. A state of prolonged high serum progesterone (pseudopregnancy) was induced in 26-day-old female rats by sequential injection of pregnant mares' serum gonadotropin and human chorionic gonadotropin. Neurosteroid withdrawal was induced by treatment with finasteride (100 mg/kg, i.p.), a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Plasma progesterone and allopregnanolone levels were measured by gas chromatography/electron capture negative chemical ionization mass spectrometry. Seizure susceptibility was evaluated with the convulsant pentylenetetrazol (PTZ). Plasma allopregnanolone levels were markedly increased during pseudopregnancy (peak level, 55.1 vs. control diestrous level, 9.3 ng/mL) and were reduced by 86% 24 h after finasteride treatment (6.4 ng/mL). Progesterone levels were unaffected by finasteride. After finasteride-induced withdrawal, rats showed increased susceptibility to PTZ seizures. There was a significant increase in the number of animals exhibiting clonic seizures when challenged with subcutaneous PTZ (60 mg/kg) compared with control pseudopregnant animals not undergoing withdrawal and nonpseudopregnant diestrous females. The CD50 (50% convulsant dose) was 46 mg/kg, compared with 73 mg/kg in nonwithdrawn pseudopregnant animals and 60 mg/kg in diestrous controls. The threshold doses for induction of various seizure signs, measured by constant intravenous infusion of PTZ, were reduced by 30-35% in neurosteroid-withdrawing animals compared with control diestrous females. No change in threshold was observed in pseudopregnant rats treated from days 7 to 11 with finasteride, demonstrating that high levels of progesterone alone do not alter seizure reactivity. Neurosteroid withdrawal in pseudopregnant rats results in enhanced seizure susceptibility, providing an animal model of perimenstrual catamenial epilepsy that can be used for the evaluation of new therapeutic approaches. JF - Epilepsia AU - Reddy, D S AU - Kim, H Y AU - Rogawski, M A AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, Maryland 20892-1408, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 328 EP - 336 VL - 42 IS - 3 SN - 0013-9580, 0013-9580 KW - Gonadotropins, Equine KW - 0 KW - Receptors, GABA KW - Steroids KW - 20-alpha-Dihydroprogesterone KW - 145-14-2 KW - Progesterone KW - 4G7DS2Q64Y KW - Finasteride KW - 57GNO57U7G KW - Pregnanolone KW - BXO86P3XXW KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Receptors, GABA -- drug effects KW - Animals KW - 20-alpha-Dihydroprogesterone -- adverse effects KW - 20-alpha-Dihydroprogesterone -- pharmacology KW - Pentylenetetrazole -- pharmacology KW - Disease Susceptibility -- epidemiology KW - Pregnanolone -- blood KW - Progesterone -- pharmacology KW - Humans KW - Receptors, GABA -- blood KW - Disease Models, Animal KW - Gonadotropins, Equine -- pharmacology KW - Pregnanolone -- pharmacology KW - Finasteride -- pharmacology KW - Gonadotropins, Equine -- blood KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Adult KW - Progesterone -- adverse effects KW - Progesterone -- blood KW - Female KW - Disease Susceptibility -- blood KW - Steroids -- adverse effects KW - Epilepsy -- blood KW - Substance Withdrawal Syndrome -- etiology KW - Menstrual Cycle -- physiology KW - Steroids -- blood KW - Pseudopregnancy -- epidemiology KW - Substance Withdrawal Syndrome -- epidemiology KW - Epilepsy -- diagnosis KW - Steroids -- pharmacology KW - Pseudopregnancy -- blood KW - Pseudopregnancy -- chemically induced KW - Epilepsy -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70984966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Neurosteroid+withdrawal+model+of+perimenstrual+catamenial+epilepsy.&rft.au=Reddy%2C+D+S%3BKim%2C+H+Y%3BRogawski%2C+M+A&rft.aulast=Reddy&rft.aufirst=D&rft.date=2001-03-01&rft.volume=42&rft.issue=3&rft.spage=328&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y in Japanese population or Japanese with alcoholism. AN - 70935026; 11409703 AB - We have screened 200 Japanese workers and 105 Japanese patients with alcoholism for the mutation in the signal peptide of pre-pro-neuropeptide Y resulting in a substitution of proline for leucine at position 7. This polymorphism was reported in the Finnish and Dutch populations recently. None of our subjects displayed the mutation at this site. Therefore, this allele does not play any role in the development of alcoholism in the Japanese population. JF - Psychiatric genetics AU - Drube, J AU - Kawamura, N AU - Nakamura, A AU - Ando, T AU - Komaki, G AU - Inada, T AD - Division of Psychosomatic Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 53 EP - 55 VL - 11 IS - 1 SN - 0955-8829, 0955-8829 KW - DNA Primers KW - 0 KW - Neuropeptide Y KW - Protein Sorting Signals KW - DNA KW - 9007-49-2 KW - Proline KW - 9DLQ4CIU6V KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Tokyo KW - DNA Mutational Analysis KW - Humans KW - Gene Amplification KW - Asian Continental Ancestry Group KW - Polymerase Chain Reaction KW - DNA -- blood KW - Molecular Sequence Data KW - Amino Acid Substitution KW - Hospitals, Psychiatric KW - Japan KW - Polymorphism, Genetic KW - Alcoholism -- genetics KW - Neuropeptide Y -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70935026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatric+genetics&rft.atitle=No+leucine%287%29-to-proline%287%29+polymorphism+in+the+signal+peptide+of+neuropeptide+Y+in+Japanese+population+or+Japanese+with+alcoholism.&rft.au=Drube%2C+J%3BKawamura%2C+N%3BNakamura%2C+A%3BAndo%2C+T%3BKomaki%2C+G%3BInada%2C+T&rft.aulast=Drube&rft.aufirst=J&rft.date=2001-03-01&rft.volume=11&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Psychiatric+genetics&rft.issn=09558829&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of DMBA induced genotoxicity in bone marrow by quercetin during skin carcinogenesis. AN - 70856463; 11370819 AB - Effect of quercetin was studied on DMBA induced skin carcinogenesis in young adult Swiss albino mice. Quercetin was administered continuously with the diet (2%) for four weeks and chromosomal aberration, a predictor of future cancer risk, studied in the bone marrow cells at different time intervals. Significant reduction of chromosomal aberration was observed in bone marrow after four weeks (P< 0.02). The reduction was first evident after 96 hrs though it was not significant at this stage. Significant decrease occurred from the 21st day onward when quercetin was given in concomitance with 7,12-dimethylbenz[a]anthracene (DMBA) indicating a definite protective effect of quercetin on chromosomal aberration. JF - Journal of experimental & clinical cancer research : CR AU - Sengupta, A AU - Ghosh, S AU - Das, S AD - Dept. of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 131 EP - 134 VL - 20 IS - 1 SN - 0392-9078, 0392-9078 KW - Antimutagenic Agents KW - 0 KW - Carcinogens KW - Mutagens KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Quercetin KW - 9IKM0I5T1E KW - Index Medicus KW - Animals KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Mice KW - Time Factors KW - Bone Marrow Cells -- drug effects KW - Antimutagenic Agents -- pharmacology KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Skin Neoplasms -- chemically induced KW - Bone Marrow Cells -- pathology KW - Chromosome Aberrations KW - Skin Neoplasms -- pathology KW - Bone Marrow Cells -- cytology KW - Quercetin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70856463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Modulation+of+DMBA+induced+genotoxicity+in+bone+marrow+by+quercetin+during+skin+carcinogenesis.&rft.au=Sengupta%2C+A%3BGhosh%2C+S%3BDas%2C+S&rft.aulast=Sengupta&rft.aufirst=A&rft.date=2001-03-01&rft.volume=20&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single amino acid substitutions on the surface of Escherichia coli maltose-binding protein can have a profound impact on the solubility of fusion proteins. AN - 70823707; 11344330 AB - Proteins are commonly fused to Escherichia coli maltose-binding protein (MBP) to enhance their yield and facilitate their purification. In addition, the stability and solubility of a passenger protein can often be improved by fusing it to MBP. In a previous comparison with two other highly soluble fusion partners, MBP was decidedly superior at promoting the solubility of a range of aggregation-prone proteins. To explain this observation, we proposed that MBP could function as a general molecular chaperone in the context of a fusion protein by binding to aggregation-prone folding intermediates of passenger proteins and preventing their self-association. The ligand-binding cleft in MBP was considered a likely site for peptide binding because of its hydrophobic nature. We tested this hypothesis by systematically replacing hydrophobic amino acid side chains in and around the cleft with glutamic acid. None of these mutations affected the yield or solubility of MBP in its unfused state. Each MBP was then tested for its ability to promote solubility when fused to three passenger proteins: green fluorescent protein, p16, and E6. Mutations within the maltose-binding cleft (W62E, A63E, Y155E, W230E, and W340E) had little or no effect on the solubility of the fusion proteins. In contrast, three mutations near one end of the cleft (W232E, Y242E, and I317E) dramatically reduced the solubility of the same fusion proteins. The mutations with the most profound effect on solubility were shown to reduce the global stability of MBP. JF - Protein science : a publication of the Protein Society AU - Fox, J D AU - Kapust, R B AU - Waugh, D S AD - Protein Engineering Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 622 EP - 630 VL - 10 IS - 3 SN - 0961-8368, 0961-8368 KW - Bacterial Proteins KW - 0 KW - Carrier Proteins KW - Escherichia coli Proteins KW - Maltose-Binding Proteins KW - Molecular Chaperones KW - Monosaccharide Transport Proteins KW - Recombinant Fusion Proteins KW - maltose transport system, E coli KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Solubility KW - Bacterial Proteins -- chemistry KW - Enzyme Stability KW - Protein Folding KW - Surface Properties KW - Carrier Proteins -- chemistry KW - Amino Acid Substitution -- genetics KW - Mutagenesis, Site-Directed -- genetics KW - Carrier Proteins -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Escherichia coli -- genetics KW - ATP-Binding Cassette Transporters KW - Recombinant Fusion Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70823707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Single+amino+acid+substitutions+on+the+surface+of+Escherichia+coli+maltose-binding+protein+can+have+a+profound+impact+on+the+solubility+of+fusion+proteins.&rft.au=Fox%2C+J+D%3BKapust%2C+R+B%3BWaugh%2C+D+S&rft.aulast=Fox&rft.aufirst=J&rft.date=2001-03-01&rft.volume=10&rft.issue=3&rft.spage=622&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1998 Sep 17;395(6699):237-43 [9751050] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9861-6 [9707566] J Mol Biol. 1999 Jan 29;285(4):1869-86 [9917418] Science. 1999 Apr 30;284(5415):822-5 [10221918] Nat Struct Biol. 1999 Jul;6(7):597-600 [10404205] Protein Sci. 1999 Aug;8(8):1668-74 [10452611] Protein Sci. 1999 Aug;8(8):1689-95 [10452613] J Mol Biol. 1999 Sep 10;292(1):163-72 [10493865] J Mol Biol. 1999 Sep 10;292(1):173-80 [10493866] J Mol Biol. 1999 Sep 10;292(1):181-90 [10493867] Cell Stress Chaperones. 1999 Sep;4(3):177-90 [10547067] Cell. 1999 Dec 23;99(7):757-68 [10619429] Cell. 2000 Jan 21;100(2):193-6 [10660042] Curr Opin Struct Biol. 2000 Feb;10(1):26-33 [10679467] Mol Biotechnol. 2000 May;15(1):51-63 [10911622] J Biol Chem. 1988 Oct 15;263(29):14790-3 [3049590] Biochemistry. 1988 Oct 18;27(21):8063-8 [3233195] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2540-4 [2539593] J Mol Biol. 1990 Jul 5;214(1):337-52 [2196376] Biochimie. 1990 Jun-Jul;72(6-7):397-402 [2124143] J Biol Chem. 1991 Mar 15;266(8):5202-19 [2002054] Eur J Biochem. 1991 Jul 15;199(2):361-9 [2070793] Biochemistry. 1992 Nov 10;31(44):10657-63 [1420181] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2266-70 [8460132] J Biol Chem. 1993 Oct 5;268(28):20855-62 [8407916] J Biol Chem. 1994 Mar 25;269(12):9284-8 [8132665] Trends Microbiol. 1994 May;2(5):170-4 [8055181] Nature. 1994 Oct 13;371(6498):614-9 [7935796] Protein Sci. 1995 Jun;4(6):1118-23 [7549876] Gene. 1996 Feb 22;169(1):59-64 [8635750] Science. 1996 Jun 14;272(5268):1606-14 [8658133] Gene. 1996;173(1 Spec No):33-8 [8707053] J Cell Biochem. 1996 Jun 1;61(3):325-37 [8761938] Protein Expr Purif. 1996 Aug;8(1):91-6 [8812839] Biochem J. 1996 Nov 1;319 ( Pt 3):713-6 [8920971] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15024-9 [8986757] Curr Biol. 1996 Dec 1;6(12):1653-63 [8994830] Protein Sci. 1997 Mar;6(3):628-36 [9070445] Biochem Biophys Res Commun. 1997 Mar 6;232(1):69-73 [9125154] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3571-5 [9108017] J Biol Chem. 1997 Jun 20;272(25):15607-12 [9188448] Protein Expr Purif. 1997 Aug;10(3):309-19 [9268677] Structure. 1997 Aug 15;5(8):997-1015 [9309217] Protein Expr Purif. 1998 Feb;12(1):122-32 [9473466] Microbiol Mol Biol Rev. 1998 Mar;62(1):204-29 [9529892] Methods Enzymol. 1998;290:444-59 [9534181] Biochem Biophys Res Commun. 1998 Mar 27;244(3):933-7 [9535771] Biochemistry. 1998 Jun 2;37(22):7929-40 [9609686] Nat Biotechnol. 1996 Mar;14(3):315-9 [9630892] Nat Biotechnol. 1996 Oct;14(10):1246-51 [9631087] Biochem J. 1998 Jul 1;333 ( Pt 1):27-32 [9639558] Biochem J. 1998 Jul 15;333 ( Pt 2):233-42 [9657960] Annu Rev Biochem. 1998;67:581-608 [9759498] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dioxin in Vietnam: fighting a legacy of war. AN - 70820587; 11333203 AB - Singapore was the site of an East-West convergence over the week of 27 November-1 December 2000. At the behest of their respective governments, scientists from the United States and Vietnam came together for what promises to be the first of many meetings. Their mission: to explore the possibility of launching a joint research program to study the human and environmental health effects resulting from spraying Agent Orange and other herbicides during the Vietnam War. JF - Environmental health perspectives AU - Booker, S M AD - NIEHS, Research Triangle Park, NC, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - A116 EP - A117 VL - 109 IS - 3 SN - 0091-6765, 0091-6765 KW - Defoliants, Chemical KW - 0 KW - Dioxins KW - Environmental Pollutants KW - Polychlorinated Dibenzodioxins KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - Agent Orange KW - 39277-47-9 KW - 2,4,5-Trichlorophenoxyacetic Acid KW - 9Q963S4YMX KW - Index Medicus KW - Warfare KW - United States KW - International Cooperation KW - Humans KW - Vietnam KW - Environmental Pollution -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70820587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Dioxin+in+Vietnam%3A+fighting+a+legacy+of+war.&rft.au=Booker%2C+S+M&rft.aulast=Booker&rft.aufirst=S&rft.date=2001-03-01&rft.volume=109&rft.issue=3&rft.spage=A116&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma pharmacokinetics and cerebrospinal fluid penetration of thioguanine in children with acute lymphoblastic leukemia: a collaborative Pediatric Oncology Branch, NCI, and Children's Cancer Group study. AN - 70806323; 11320662 AB - In preclinical studies, thioguanine (TG) has been shown to be more potent than the standard acute lymphoblastic leukemia (ALL) maintenance agent, mercaptopurine (MP), suggesting that TG may be more efficacious than MP in the treatment of childhood ALL. As part of a pilot trial in which TG was used in place of MP, we studied the plasma pharmacokinetics of oral TG and measured steady-state plasma and CSF TG concentrations during a continuous intravenous infusion (CIVI) in children with newly diagnosed standard-risk ALL. Nine plasma samples were collected after each patient's first 60 mg/m2 oral TG dose during maintenance. CIVI TG (20 mg/m2/h over 24 h) was administered during the consolidation phase of therapy, and simultaneous plasma and CSF samples were collected near the end of the infusion. TG was measured by reverse-phase HPLC with ultraviolet detection. Erythrocyte TG nucleotide (TGN) concentrations were measured 7 days after a course of CIVI TG and prior to the start of each maintenance cycle. After oral TG (n = 35), the mean (+/- SD) peak plasma concentration was 0.46 +/- 0.68 microM and the AUC ranged from 0.18 to 9.5 microM.h (mean 1.5 microM.h). Mean steady-state plasma and CSF TG concentrations during CIVI (n = 33) were 2.7 and 0.5 microM, respectively. The mean (+/- SD) TG clearance was 935 +/- 463 ml/min per m2. Plasma TG concentrations did not correlate with erythrocyte TGN concentrations after oral or CIVI TG. The 8-OH-TG metabolite was detected in plasma and CSF. TG concentrations that are cytotoxic to human leukemia cell lines can be achieved in plasma after a 60 mg/m2 oral dose of TG and in plasma and CSF during CIVI of TG. JF - Cancer chemotherapy and pharmacology AU - Lowe, E S AU - Kitchen, B J AU - Erdmann, G AU - Stork, L C AU - Bostrom, B C AU - Hutchinson, R AU - Holcenberg, J AU - Reaman, G H AU - Woods, W AU - Franklin, J AU - Widemann, B C AU - Balis, F M AU - Murphy, R F AU - Adamson, P C AD - Pediatric Oncology Branch, National Cancer Institute, 10 Center Drive, Building 10, Room 13C103, Bethesda, MD 20892, USA. lowee@mail.nih.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 199 EP - 205 VL - 47 IS - 3 SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Administration, Oral KW - Infusions, Intravenous KW - Area Under Curve KW - Humans KW - Chromatography, High Pressure Liquid -- methods KW - Pilot Projects KW - Erythrocytes -- metabolism KW - Thioguanine -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- urine KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- metabolism KW - Thioguanine -- urine KW - Antimetabolites, Antineoplastic -- cerebrospinal fluid KW - Thioguanine -- cerebrospinal fluid KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Thioguanine -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70806323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Plasma+pharmacokinetics+and+cerebrospinal+fluid+penetration+of+thioguanine+in+children+with+acute+lymphoblastic+leukemia%3A+a+collaborative+Pediatric+Oncology+Branch%2C+NCI%2C+and+Children%27s+Cancer+Group+study.&rft.au=Lowe%2C+E+S%3BKitchen%2C+B+J%3BErdmann%2C+G%3BStork%2C+L+C%3BBostrom%2C+B+C%3BHutchinson%2C+R%3BHolcenberg%2C+J%3BReaman%2C+G+H%3BWoods%2C+W%3BFranklin%2C+J%3BWidemann%2C+B+C%3BBalis%2C+F+M%3BMurphy%2C+R+F%3BAdamson%2C+P+C&rft.aulast=Lowe&rft.aufirst=E&rft.date=2001-03-01&rft.volume=47&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bisimidazoacridones induce a potent cytostatic effect in colon tumor cells that sensitizes them to killing by UCN-01. AN - 70770853; 11320668 AB - To determine the ability of WMC26, a prototypic bisimidazoacridone (BIA), to induce apoptosis in sensitive colon adenocarcinoma cells and to advance the hypothesis that cancer cells that are growth-arrested by WMC26 are predisposed to undergo apoptotic death by abrogators of cell cycle checkpoints. The antiproliferative activity of WMC26 was examined in detail by a 4-day MTT assay, cell counting, BrdU incorporation and a two-color LIVE/DEAD assay. To detect apoptosis a number of established techniques were used, including gel electrophoresis, flow cytometry, and confocal laser microscopy of treated cells. The activity of senescence-associated beta-galactosidase in treated cells was also analyzed. WMC26, at physiological concentrations, induced complete and longlasting growth arrest of HCT116 cells in culture but did not trigger cell death. The growth-arrested cells (blocked at G1 and G2/M cell cycle checkpoints) did not synthesize DNA but were metabolically active and had intact plasma membranes. Although they resembled the senescence-like phenotype reported to be induced by treatment with some antitumor agents, the cells did not express senescence-associated beta-galactosidase, an indicator of the senescence-like state. Treatment of WMC26 growth-arrested cells with 1 microM UCN-01, an abrogator of the G2/M checkpoint, caused a very rapid (1 h) change in morphology and cell death within 72 h. BIAs do not induce apoptosis in sensitive colon tumor cells. They are highly cytostatic but only marginally toxic to the cells even at concentrations 100-fold higher than those sufficient for complete growth arrest. In this respect WMC26 differs from some other DNA-interacting antitumor agents that produce cell growth arrest at low concentrations but are toxic at higher doses. The complete growth arrest induced by WMC26 in colon cancer cells sensitized them to apoptotic death induced by UCN-01. This finding suggests that a combination of WMC26 and cyclin-dependent kinase inhibitors may be an attractive treatment method for colon cancer that utilizes the highly tumor-selective activity of WMC26. JF - Cancer chemotherapy and pharmacology AU - Cholody, W M AU - Kosakowska-Cholody, T AU - Michejda, C J AD - Structural Biophysics Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 241 EP - 249 VL - 47 IS - 3 SN - 0344-5704, 0344-5704 KW - Aminoacridines KW - 0 KW - Antimetabolites, Antineoplastic KW - Antineoplastic Agents KW - Coloring Agents KW - WMC 26 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - beta-Galactosidase -- metabolism KW - Tumor Cells, Cultured KW - Cell Count KW - Humans KW - Cell Division -- drug effects KW - Antimetabolites, Antineoplastic -- metabolism KW - Cell Cycle -- drug effects KW - Caspases -- metabolism KW - Bromodeoxyuridine -- metabolism KW - Adenocarcinoma -- enzymology KW - Colonic Neoplasms -- drug therapy KW - Aminoacridines -- therapeutic use KW - Colonic Neoplasms -- pathology KW - Cell Death -- drug effects KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents -- pharmacology KW - Colonic Neoplasms -- enzymology KW - Aminoacridines -- pharmacology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70770853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Bisimidazoacridones+induce+a+potent+cytostatic+effect+in+colon+tumor+cells+that+sensitizes+them+to+killing+by+UCN-01.&rft.au=Cholody%2C+W+M%3BKosakowska-Cholody%2C+T%3BMichejda%2C+C+J&rft.aulast=Cholody&rft.aufirst=W&rft.date=2001-03-01&rft.volume=47&rft.issue=3&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QTc prolongation. AN - 70671855; 11240972 AB - Nefazodone inhibits CYP3A; therefore coadministration with CYP3A substrates such as terfenadine or loratadine may result in increased exposure to these drugs. A potential pharmacodynamic consequence is electrocardiographic QTc prolongation, which has been associated with torsade de pointes cardiac arrhythmia. Therefore a clinical pharmacokinetic-pharmacodynamic evaluation of this potential interaction was conducted. A randomized, double-blind, double-dummy, parallel group, multiple-dose design was used. Healthy men and women who were given doses of 60 mg of terfenadine every 12 hours, 20 mg of loratadine once daily, and 300 mg of nefazodone every 12 hours were studied. Descriptive pharmacokinetics (time to maximum concentration, maximum concentration, and area under the plasma concentration-time curve) were used for the examination of interactions among the respective parent drugs and metabolites. QTc prolongation (mean value over the dosing interval) was the pharmacodynamic parameter measured. Kinetic and dynamic analysis was used for the examination of pooled concentration and QTc data with the use of a linear model. Concomitant nefazodone treatment markedly increased the dose interval area under the plasma concentration-time curve of both terfenadine (mean value, 17.3 +/- 8.5 ng. mL/h versus 97.4 +/- 48.9 ng. mL/h; P <.001) and carboxyterfenadine (mean value, 1.69 +/- 0.48 microg. h/mL versus 2.88 +/- 0.53 microg. h/mL; P <.001) and moderately increased the dose interval area under the plasma concentration-time curve of both loratadine (mean value, 31.5 +/- 27.9 ng. h/mL versus 43.7 +/- 25.9 ng. h/mL; P <.014) and descarboethoxyloratadine (mean value, 73.4 +/- 54.9 ng. h/mL versus 81.9 +/- 26.2 ng. h/mL; P <.002). The mean QTc was unchanged with terfenadine alone; however, it was markedly prolonged with concomitant nefazodone and terfenadine (mean [90% confidence interval] prolongation 42.4 ms [34.2, 50.6 ms]; P <.05). Similarly, the mean QTc was unchanged with loratadine alone; however, it was prolonged with concomitant nefazodone and loratadine (21.6 ms [13.7, 29.4 ms]; P <.05). Nefazodone alone did not change mean QTc. QTc was positively correlated with terfenadine plasma concentration (r (2) = 0.21; P =.0001). Similarly, QTc was positively correlated with loratadine plasma concentration (r (2) = 0.056; P =.0008) but with a flatter slope. There was no relationship between QTc and nefazodone plasma concentration during treatment with nefazodone alone (r (2) = 0.002, not significant). In healthy men and women, concomitant nefazodone treatment at a therapeutic dose increases exposure to both terfenadine and carboxyterfenadine. This increased exposure is associated with marked QTc prolongation, which is correlated with terfenadine plasma concentration. A similar interaction occurs with loratadine, although it is of lesser magnitude. Concomitant administration of nefazodone with terfenadine may have predisposed individuals to the arrhythmia associated with QTc prolongation, torsade de pointes, when terfenadine was available for clinical use. However, a new finding is that in the context of higher than clinically recommended daily doses (20 mg) of loratadine concomitant administration with a metabolic inhibitor such as nefazodone can also result in QTc prolongation. JF - Clinical pharmacology and therapeutics AU - Abernethy, D R AU - Barbey, J T AU - Franc, J AU - Brown, K S AU - Feirrera, I AU - Ford, N AU - Salazar, D E AD - Division of Clinical Pharmacology, Georgetown University School of Medicine, the National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224-6825, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 96 EP - 103 VL - 69 IS - 3 SN - 0009-9236, 0009-9236 KW - Antidepressive Agents, Second-Generation KW - 0 KW - Histamine H1 Antagonists KW - Triazoles KW - nefazodone KW - 59H4FCV1TF KW - Loratadine KW - 7AJO3BO7QN KW - Terfenadine KW - 7BA5G9Y06Q KW - Abridged Index Medicus KW - Index Medicus KW - Drug Interactions KW - Double-Blind Method KW - Area Under Curve KW - Humans KW - Linear Models KW - Adult KW - Middle Aged KW - Male KW - Female KW - Antidepressive Agents, Second-Generation -- pharmacology KW - Histamine H1 Antagonists -- pharmacokinetics KW - Loratadine -- pharmacology KW - Loratadine -- pharmacokinetics KW - Terfenadine -- pharmacology KW - Histamine H1 Antagonists -- pharmacology KW - Terfenadine -- pharmacokinetics KW - Antidepressive Agents, Second-Generation -- pharmacokinetics KW - Triazoles -- pharmacology KW - Triazoles -- pharmacokinetics KW - Electrocardiography -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70671855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Loratadine+and+terfenadine+interaction+with+nefazodone%3A+Both+antihistamines+are+associated+with+QTc+prolongation.&rft.au=Abernethy%2C+D+R%3BBarbey%2C+J+T%3BFranc%2C+J%3BBrown%2C+K+S%3BFeirrera%2C+I%3BFord%2C+N%3BSalazar%2C+D+E&rft.aulast=Abernethy&rft.aufirst=D&rft.date=2001-03-01&rft.volume=69&rft.issue=3&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=00099236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Pharmacol Ther. 2001 Dec;70(6):567-8 [11753275] Clin Pharmacol Ther. 2002 May;71(5):403; author reply 403 [12011827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the neurotrophic interaction between nerve growth factor and secreted alpha-amyloid precursor protein. AN - 70667383; 11223916 AB - The expression and secretion of amyloid precursor protein (beta APP) is increased in rat cerebral cortices that have been denervated by subcortical lesions of the nucleus basalis of Meynert. The physiological role of the secreted beta APP in response to this injury has not been established. We have previously shown that secreted beta APP produced by alpha-secretase activity (sAPP(alpha)) potentiates the neuritogenic activity of nerve growth factor (NGF) in vitro on naive PC12 cells. In this investigation, we have further characterized the neurotrophic interaction of NGF and sAPP(alpha) using differentiated PC12 cells and rat primary cortical neurons. NGF required the expression of beta APP to maintain a neuronal phenotype. Reduction of endogenous beta APP expression by introduction of antisense oligonucleotides in the presence of NGF resulted in loss of neurites from differentiated PC12 cells but no apparent cell death. Addition of exogenous sAPP(alpha) (60--200 pM) potentiated the protective activity of NGF in serum-deprived differentiated PC12 cells as determined by retention of neurites and cell viability. In addition, exogenous sAPP(alpha) increased neuron viability in both short-term (3 days) cortical neuron cultures grown in the absence of serum and in long-term (9 days) cultures grown with serum. Disruption of the insulin signaling pathway by reduction of IRS-1 expression inhibited the ability of sAPP(alpha) to potentiate neurotrophic activity. These observations suggest that sAPP(alpha) acts as an injury-induced neurotrophic factor that interacts with NGF to enhance neuronal viability using the insulin signaling pathway. Copyright 2001 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Luo, J J AU - Wallace, M S AU - Hawver, D B AU - Kusiak, J W AU - Wallace, W C AD - Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 410 EP - 420 VL - 63 IS - 5 SN - 0360-4012, 0360-4012 KW - Amyloid beta-Protein Precursor KW - 0 KW - Coloring Agents KW - Culture Media KW - Fluorescent Dyes KW - Growth Substances KW - IRS1 protein, human KW - Insulin KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, rat KW - Oligodeoxyribonucleotides, Antisense KW - Organic Chemicals KW - Phosphoproteins KW - SYTOX Green KW - Nerve Growth Factor KW - 9061-61-4 KW - Amyloid Precursor Protein Secretases KW - EC 3.4.- KW - Endopeptidases KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - BACE1 protein, human KW - EC 3.4.23.46 KW - Index Medicus KW - Animals KW - PC12 Cells -- metabolism KW - Humans KW - Endopeptidases -- pharmacology KW - Endopeptidases -- physiology KW - Oligodeoxyribonucleotides, Antisense -- pharmacology KW - Culture Media -- pharmacology KW - Rats KW - Phenotype KW - Neurites -- ultrastructure KW - Horses -- blood KW - Drug Synergism KW - Cell Differentiation -- drug effects KW - Signal Transduction KW - PC12 Cells -- drug effects KW - Cattle KW - Neurites -- drug effects KW - Fetal Blood KW - Growth Substances -- pharmacology KW - Growth Substances -- blood KW - Cerebral Cortex -- secretion KW - Phosphoproteins -- genetics KW - Insulin -- physiology KW - Phosphoproteins -- physiology KW - Amyloid beta-Protein Precursor -- secretion KW - Basal Nucleus of Meynert -- injuries KW - Insulin -- pharmacology KW - Amyloid beta-Protein Precursor -- genetics KW - Nerve Growth Factor -- pharmacology KW - Basal Nucleus of Meynert -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70667383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Characterization+of+the+neurotrophic+interaction+between+nerve+growth+factor+and+secreted+alpha-amyloid+precursor+protein.&rft.au=Luo%2C+J+J%3BWallace%2C+M+S%3BHawver%2C+D+B%3BKusiak%2C+J+W%3BWallace%2C+W+C&rft.aulast=Luo&rft.aufirst=J&rft.date=2001-03-01&rft.volume=63&rft.issue=5&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacteriophage K1-5 encodes two different tail fiber proteins, allowing it to infect and replicate on both K1 and K5 strains of Escherichia coli. AN - 70663303; 11222673 AB - A virulent double-stranded DNA bacteriophage, Phi K1-5, has been isolated and found to be capable of infecting Escherichia coli strains that possess either the K1 or the K5 polysaccharide capsule. Electron micrographs show that the virion consists of a small icosohedral head with short tail spikes, similar to members of the Podoviridae family. DNA sequence analysis of the region encoding the tail fiber protein showed two open reading frames encoding previously characterized hydrolytic phage tail fiber proteins. The first is the K5 lyase protein gene of Phi K5, which allows this phage to specifically infect K5 E. coli strains. A second open reading frame encodes a protein almost identical in amino acid sequence to the N-acetylneuraminidase (endosialidase) protein of Phi K1E, which allows this phage to specifically infect K1 strains of E. coli. We provide experimental evidence that mature phage particles contain both tail fiber proteins, and mutational analysis indicates that each protein can be independently inactivated. A comparison of the tail gene regions of Phi K5, Phi K1E, and Phi K1-5 shows that the genes are arranged in a modular or cassette configuration and suggests that this family of phages can broaden host range by horizontal gene transfer. JF - Journal of virology AU - Scholl, D AU - Rogers, S AU - Adhya, S AU - Merril, C R AD - National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 2509 EP - 2515 VL - 75 IS - 6 SN - 0022-538X, 0022-538X KW - Antigens, Bacterial KW - 0 KW - Antigens, Surface KW - K antigens KW - Polysaccharides, Bacterial KW - Sewage KW - Viral Tail Proteins KW - capsular polysaccharide K1 KW - Index Medicus KW - Virus Replication KW - Base Sequence KW - Sewage -- virology KW - Bacterial Capsules KW - Molecular Sequence Data KW - Virion -- metabolism KW - Mutation KW - Coliphages -- isolation & purification KW - Escherichia coli -- metabolism KW - Viral Tail Proteins -- genetics KW - Viral Tail Proteins -- metabolism KW - Coliphages -- physiology KW - Escherichia coli -- virology KW - Coliphages -- genetics KW - Polysaccharides, Bacterial -- metabolism KW - Antigens, Surface -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70663303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Bacteriophage+K1-5+encodes+two+different+tail+fiber+proteins%2C+allowing+it+to+infect+and+replicate+on+both+K1+and+K5+strains+of+Escherichia+coli.&rft.au=Scholl%2C+D%3BRogers%2C+S%3BAdhya%2C+S%3BMerril%2C+C+R&rft.aulast=Scholl&rft.aufirst=D&rft.date=2001-03-01&rft.volume=75&rft.issue=6&rft.spage=2509&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF322019; GENBANK; AF322018; AF322020 N1 - SuppNotes - Cited By: J Virol. 1985 Aug;55(2):374-8 [3894684] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Rev Infect Dis. 1987 Sep-Oct;9 Suppl 5:S517-26 [2446369] J Mol Biol. 1988 Mar 20;200(2):351-65 [3259634] J Bacteriol. 1989 Aug;171(8):4378-84 [2526805] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] J Mol Biol. 1990 Nov 20;216(2):327-34 [2147721] FEMS Microbiol Lett. 1991 Aug 1;66(2):137-41 [1936942] J Bacteriol. 1992 Mar;174(5):1462-77 [1531648] Zentralbl Bakteriol. 1992 Jan;276(2):213-20 [1559009] J Bacteriol. 1993 Mar;175(5):1272-7 [8444789] J Bacteriol. 1993 Jul;175(14):4354-63 [8331067] J Clin Microbiol. 1994 Nov;32(11):2843-5 [7852583] Biochem J. 1995 Jul 15;309 ( Pt 2):543-50 [7626018] J Mol Biol. 1996 May 24;258(5):726-31 [8637004] J Bacteriol. 1996 Aug;178(15):4747-50 [8755913] J Mol Biol. 1997 Mar 28;267(2):237-49 [9096222] Gene. 1997 Aug 11;195(1):93-100 [9300826] Mol Microbiol. 1997 Oct;26(1):49-64 [9383189] Virology. 1998 Feb 1;241(1):61-72 [9454717] Can J Microbiol. 1997 Dec;43(12):1147-56 [9476351] Virology. 1998 Feb 15;241(2):345-56 [9499809] J Struct Biol. 1998;122(1-2):216-22 [9724623] J Mol Biol. 1998 Sep 25;282(3):543-56 [9737921] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2192-7 [10051617] FEMS Microbiol Lett. 2000 Jan 15;182(2):333-7 [10620688] J Bacteriol. 2000 Jul;182(13):3761-6 [10850992] J Mol Biol. 2000 May 26;299(1):27-51 [10860721] J Clin Microbiol. 1977 Dec;6(6):548-50 [338623] J Gen Virol. 1978 Sep;40(3):669-73 [357683] J Mol Biol. 1980 Jun 5;139(4):679-90 [6997499] Ann N Y Acad Sci. 1980;354:484-90 [6452848] Nucleic Acids Res. 1986 Apr 25;14(8):3521-6 [3010240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exchange of the basic domain of human immunodeficiency virus type 1 Rev for a polyarginine stretch expands the RNA binding specificity, and a minimal arginine cluster is required for optimal RRE RNA binding affinity, nuclear accumulation, and trans-activation. AN - 70651378; 11222721 AB - The Rev regulatory protein of human immunodeficiency virus (HIV) facilitates the nuclear export of unspliced and partially spliced HIV RNAs. Using a Rev:MS2 phage coat protein fusion that could be targeted to bind and activate the Rev-responsive element (RRE) RNA or heterologous MS2 phage operator RNA, we analyzed the role(s) of the arginine-rich RNA binding domain in RNA binding and transactivation. The arginine-rich domain could be functionally replaced by a stretch of nine arginines. However, polyarginine substitutions expanded the RNA binding specificity of the resultant mutant Rev protein. Polyarginine insertions in place of residues 24 to 60 that excised the RNA binding and oligomerization domains of Rev preserved the activation for MS2 RNA, but not for the RRE. A nine-arginine insertion outside of the natural context of the Rev nuclear localization signal domain was incompatible with activation of either RNA target. Insertions of fewer than eight arginines impaired RRE activation. Interrupted lysine clusters and disruption of the arginine stretch with lysine or neutral residues resulted in a similar phenotype. Some of these mutants with a null phenotype for RRE activated the heterologous MS2 RNA target. Under steady-state conditions, mutants that preserved the Rev response for RRE RNA localized to the nuclei; those with poor or no Rev response accumulated mostly in the cytoplasm. Many of the cytoplasmically resident derivatives became nuclear when leptomycin B (LMB) treatment inhibited nuclear export of nuclear export signal-containing proteins. Mutants that had a null activation potential for either RNA target were particularly resistant to LMB treatment. Abbreviated nuclear residence times and differences in RRE binding affinity may have compromised their activation potential for RRE. High-affinity binding to MS2 RNA through the intact coat protein was sufficient to overcome the short nuclear residence times and to facilitate MS2 activation by some derivatives. JF - Journal of virology AU - Nam, Y S AU - Petrovic, A AU - Jeong, K S AU - Venkatesan, S AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 2957 EP - 2971 VL - 75 IS - 6 SN - 0022-538X, 0022-538X KW - Capsid Proteins KW - 0 KW - Gene Products, rev KW - Nuclear Localization Signals KW - Peptides KW - RNA, Viral KW - RNA-Binding Proteins KW - Recombinant Fusion Proteins KW - rev Gene Products, Human Immunodeficiency Virus KW - polyarginine KW - 25212-18-4 KW - Arginine KW - 94ZLA3W45F KW - Index Medicus KW - Animals KW - Cell Nucleus -- metabolism KW - Capsid KW - Humans KW - Multigene Family KW - Plasmids KW - Transcriptional Activation KW - Recombinant Fusion Proteins -- metabolism KW - Genes, rev KW - Protein Structure, Tertiary KW - Cell Line KW - Mutagenesis, Insertional KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - HIV-1 -- chemistry KW - Gene Products, rev -- metabolism KW - Gene Products, rev -- genetics KW - Genes, env KW - Gene Products, rev -- chemistry KW - RNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70651378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Exchange+of+the+basic+domain+of+human+immunodeficiency+virus+type+1+Rev+for+a+polyarginine+stretch+expands+the+RNA+binding+specificity%2C+and+a+minimal+arginine+cluster+is+required+for+optimal+RRE+RNA+binding+affinity%2C+nuclear+accumulation%2C+and+trans-activation.&rft.au=Nam%2C+Y+S%3BPetrovic%2C+A%3BJeong%2C+K+S%3BVenkatesan%2C+S&rft.aulast=Nam&rft.aufirst=Y&rft.date=2001-03-01&rft.volume=75&rft.issue=6&rft.spage=2957&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1998 Feb 20;92(4):451-62 [9491887] J Virol. 1998 Apr;72(4):2935-44 [9525614] Exp Cell Res. 1998 Aug 1;242(2):540-7 [9683540] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10608-13 [9724751] Genes Dev. 1998 Nov 15;12(22):3512-27 [9832504] J Biol Chem. 1998 Dec 11;273(50):33414-22 [9837918] Cell. 1991 Apr 19;65(2):241-8 [2015625] J Acquir Immune Defic Syndr. 1991;4(6):558-67 [2023097] Nucleic Acids Res. 1991 Apr 11;19(7):1577-83 [2027765] Prog Nucleic Acid Res Mol Biol. 1991;40:185-220 [2031083] Science. 1991 May 24;252(5009):1167-71 [1709522] J Virol. 1991 Aug;65(8):4248-54 [2072452] Biochemistry. 1991 Jul 30;30(30):7527-34 [1854752] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7366-70 [1871141] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7734-8 [1715576] J Virol. 1991 Nov;65(11):6001-7 [1920623] Cell. 1991 Nov 1;67(3):529-36 [1934059] J Virol. 1991 Dec;65(12):7051-5 [1942257] Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):758-62 [1731351] EMBO J. 1992 Mar;11(3):1119-29 [1547776] J Virol. 1992 Apr;66(4):1849-55 [1548742] J Virol. 1992 Apr;66(4):2510-3 [1548775] J Virol. 1992 Apr;66(4):2583-7 [1548784] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2723-6 [1557378] J Virol. 1992 Jun;66(6):3699-706 [1583728] J Exp Med. 1992 Oct 1;176(4):1197-201 [1402661] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9870-4 [1409715] Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071-5 [2832844] J Virol. 1989 Mar;63(3):1265-74 [2783738] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] J Virol. 1989 May;63(5):1959-66 [2704072] Cell. 1989 Jun 30;57(7):1155-65 [2736624] Cell. 1989 Jul 14;58(1):205-14 [2752419] Cell. 1989 Dec 1;59(5):789-95 [2686839] Nature. 1989 Dec 7;342(6250):714-6 [2556643] Nature. 1989 Dec 14;342(6251):816-9 [2481237] J Virol. 1990 Feb;64(2):881-5 [2404140] Cell. 1990 Feb 23;60(4):675-83 [2406030] Cell. 1990 Feb 23;60(4):685-93 [1689218] Nature. 1990 May 3;345(6270):36-41 [2330049] Nucleic Acids Res. 1990 Apr 25;18(8):2037-44 [2186373] Virology. 1990 Sep;178(1):327-30 [2202148] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787-91 [2217212] Genes Dev. 1990 Aug;4(8):1357-64 [2227413] J Virol. 1990 Dec;64(12):5966-75 [2243382] J Virol. 1991 Jan;65(1):81-8 [1985219] Biochemistry. 1990 Dec 18;29(50):11051-7 [1703010] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):683-7 [1992459] Genes Dev. 1991 Feb;5(2):201-10 [1899841] J Virol. 1991 Apr;65(4):2131-4 [2002556] EMBO J. 1993 Feb;12(2):595-600 [8440248] Cell. 1993 Jun 4;73(5):1031-40 [7684657] Mol Cell Biol. 1993 Oct;13(10):6180-9 [8105371] J Cell Biol. 1993 Dec;123(6 Pt 1):1309-20 [8253832] J Mol Biol. 1993 Dec 5;234(3):620-39 [8254664] Biochemistry. 1994 Mar 15;33(10):2741-7 [8130185] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4713-7 [7515177] Virology. 1994 Jul;202(1):186-94 [7516596] J Mol Biol. 1994 Aug 12;241(2):193-207 [8057359] J Virol. 1994 Sep;68(9):5433-8 [8057425] Virology. 1994 Oct;204(1):123-31 [8091647] J Virol. 1994 Nov;68(11):7329-35 [7523698] Mol Cell Biol. 1994 Nov;14(11):7436-44 [7935458] Genes Dev. 1994 Jul 1;8(13):1538-47 [7958838] Biochemistry. 1994 Dec 6;33(48):14579-85 [7981219] Exp Cell Res. 1995 Mar;217(1):31-41 [7867718] Structure. 1995 Mar 15;3(3):255-63 [7788292] Cell. 1995 Aug 11;82(3):485-94 [7634337] Nature. 1995 Aug 10;376(6540):530-3 [7637788] J Mol Biol. 1995 Oct 20;253(2):243-58 [7563086] Hum Gene Ther. 1995 May;6(5):625-34 [7578399] EMBO J. 1996 Apr 15;15(8):1810-7 [8617226] EMBO J. 1996 Apr 15;15(8):1818-25 [8617227] Science. 1996 Sep 13;273(5281):1547-51 [8703216] Chem Biol. 1997 Feb;4(2):139-47 [9190288] Protein Eng. 1997 Feb;10(2):103-7 [9089809] J Virol. 1992 Dec;66(12):7232-8 [1433516] J Virol. 1992 Dec;66(12):7469-80 [1433526] Nucleic Acids Res. 1992 Oct 25;20(20):5465-72 [1437564] Mol Cell Biol. 1999 Feb;19(2):1210-7 [9891055] Mol Cell Biol. 1999 Feb;19(2):1218-25 [9891056] Arch Biochem Biophys. 1999 May 15;365(2):175-85 [10328810] J Biol Chem. 1999 Jun 18;274(25):17452-63 [10364175] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9112-7 [10430904] Arch Virol. 2000;145(12):2443-67 [11205098] Biochemistry. 1983 May 24;22(11):2601-10 [6347247] Nature. 1986 May 22-28;321(6068):412-7 [3012355] Cell. 1986 Sep 12;46(6):807-17 [3638988] Science. 1987 May 15;236(4803):837-40 [3033827] Biochemistry. 1987 Mar 24;26(6):1563-8 [3297131] J Biol Chem. 1997 Aug 22;272(34):21548-57 [9261175] Science. 1997 Oct 3;278(5335):141-4 [9311922] Cell. 1997 Sep 19;90(6):1041-50 [9323132] Cell. 1997 Sep 19;90(6):1051-60 [9323133] Biochemistry. 1997 Oct 28;36(43):13256-62 [9341215] Nature. 1997 Nov 20;390(6657):308-11 [9384386] J Mol Biol. 1997 Dec 19;274(5):693-707 [9405152] Mol Cell Biol. 1998 Mar;18(3):1449-58 [9488461] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus. AN - 70651218; 11222690 AB - The chimeric murine oncornavirus FrCas(E) causes a rapidly progressive paralytic disease associated with spongiform neurodegeneration throughout the neuroaxis. Neurovirulence is determined by the sequence of the viral envelope gene and by the capacity of the virus to infect microglia. The neurocytopathic effect of this virus appears to be indirect, since the cells which degenerate are not infected. In the present study we have examined the possible role of inflammatory responses in this disease and have used as a control the virus F43. F43 is an highly neuroinvasive but avirulent virus which differs from FrCas(E) only in 3' pol and env sequences. Like FrCas(E), F43 infects large numbers of microglial cells, but it does not induce spongiform neurodegeneration. RNAase protection assays were used to detect differential expression of genes encoding a variety of cytokines, chemokines, and inflammatory cell-specific markers. Tumor necrosis factor alpha (TNF-alpha) and TNF-beta mRNAs were upregulated in advanced stages of disease but not early, even in regions with prominent spongiosis. Surprisingly there was no evidence for upregulation of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6 or of the microglial marker F4/80 at any stage of this disease. In contrast, increased levels of the beta-chemokines MIP-1 alpha and -beta were seen early in the disease and were concentrated in regions of the brain rich in spongiosis, and the magnitude of responses was similar to that observed in the brains of mice injected with the glutamatergic neurotoxin ibotenic acid. MIP-1alpha and MIP-1beta mRNAs were also upregulated in F43-inoculated mice, but the responses were three- to fivefold lower and occurred later in the course of infection than was observed in FrCas(E)-inoculated mice. These results suggest that the robust increase in expression of MIP-1 alpha and MIP-1 beta in the brain represents a correlate of neurovirulence in this disease, whereas the TNF responses are likely secondary events. JF - Journal of virology AU - Askovic, S AU - Favara, C AU - McAtee, F J AU - Portis, J L AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 2665 EP - 2674 VL - 75 IS - 6 SN - 0022-538X, 0022-538X KW - Chemokine CCL3 KW - 0 KW - Chemokine CCL4 KW - Chemokines, CC KW - Macrophage Inflammatory Proteins KW - RNA, Messenger KW - Ibotenic Acid KW - 2552-55-8 KW - Index Medicus KW - Virulence KW - Animals KW - Chemokines, CC -- metabolism KW - RNA, Messenger -- metabolism KW - Neurons -- drug effects KW - Neurons -- physiology KW - Mice KW - RNA, Messenger -- genetics KW - Cell Death -- drug effects KW - Immunohistochemistry KW - Inflammation KW - Ibotenic Acid -- pharmacology KW - Retroviridae Infections -- virology KW - Retroviridae -- pathogenicity KW - Macrophage Inflammatory Proteins -- metabolism KW - Retroviridae Infections -- immunology KW - Neurodegenerative Diseases -- virology KW - Macrophage Inflammatory Proteins -- genetics KW - Brain -- pathology KW - Neurodegenerative Diseases -- immunology KW - Neurodegenerative Diseases -- pathology KW - Brain -- virology KW - Brain -- immunology KW - Retroviridae Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70651218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Increased+expression+of+MIP-1+alpha+and+MIP-1+beta+mRNAs+in+the+brain+correlates+spatially+and+temporally+with+the+spongiform+neurodegeneration+induced+by+a+murine+oncornavirus.&rft.au=Askovic%2C+S%3BFavara%2C+C%3BMcAtee%2C+F+J%3BPortis%2C+J+L&rft.aulast=Askovic&rft.aufirst=S&rft.date=2001-03-01&rft.volume=75&rft.issue=6&rft.spage=2665&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuron. 1991 Sep;7(3):365-79 [1654946] J Virol. 1991 May;65(5):2539-44 [1850027] J Virol. 1992 Jun;66(6):3298-305 [1316449] Trends Neurosci. 1993 Jul;16(7):268-73 [7689770] J Virol. 1993 Nov;67(11):6648-58 [8411367] J Virol. 1994 Apr;68(4):2383-7 [8139024] Lab Invest. 1994 May;70(5):711-23 [8196367] Mol Chem Neuropathol. 1994 Aug;22(3):143-60 [7993524] J Virol. 1995 Mar;69(3):1408-19 [7853473] J Neuropathol Exp Neurol. 1995 May;54(3):358-70 [7745435] J Immunol. 1995 Dec 15;155(12):5769-76 [7499865] J Immunol. 1996 Jun 1;156(11):4363-8 [8666808] Neuroscience. 1996 Sep;74(1):1-5 [8843071] Neuroscience. 1996 Sep;74(1):283-92 [8843093] Trends Neurosci. 1996 Aug;19(8):312-8 [8843599] Brain Res Brain Res Rev. 1995 Sep;21(2):195-218 [8866675] Am J Pathol. 1996 Nov;149(5):1459-67 [8909235] Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13345-50 [8917593] J Virol. 1996 Dec;70(12):8896-907 [8971019] J Comp Neurol. 1997 Feb 3;378(1):70-87 [9120055] Brain Res. 1998 Jan 1;779(1-2):1-8 [9473560] Neurosci Lett. 1998 Jan 23;241(1):53-6 [9502214] J Immunol. 1998 Jan 15;160(2):970-8 [9551936] J Neuroimmunol. 1998 Aug 1;88(1-2):154-64 [9688337] Virology. 1998 Aug 1;247(2):127-36 [9705905] Ann Neurol. 1998 Sep;44(3 Suppl 1):S115-20 [9749582] Ann Neurol. 1998 Nov;44(5):831-5 [9818943] J Neurovirol. 1999 Feb;5(1):65-75 [10190692] Semin Immunol. 1999 Apr;11(2):125-37 [10329499] J Virol. 2000 Jan;74(1):465-73 [10590136] J Neurovirol. 1999 Dec;5(6):635-42 [10602404] J Immunol Methods. 2000 Feb 3;234(1-2):149-51 [10669779] Virology. 2000 Jun 5;271(2):227-33 [10860875] Am J Pathol. 1972 Sep;68(3):626-52 [4626566] J Natl Cancer Inst. 1973 Oct;51(4):1243-54 [4355605] J Neuropathol Exp Neurol. 1974 Apr;33(2):285-307 [4362701] Neuropathol Appl Neurobiol. 1981 Sep-Oct;7(5):365-80 [6272148] J Virol. 1984 Nov;52(2):448-56 [6092670] J Virol. 1984 Nov;52(2):695-8 [6092693] J Virol. 1984 Dec;52(3):734-8 [6092705] J Neuroimmunol. 1986 May;11(3):251-7 [2420825] Proc Natl Acad Sci U S A. 1989 May;86(10):3896-900 [2542954] J Virol. 1990 Apr;64(4):1648-56 [2181155] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1281-5 [1847516] J Immunol. 1992 Jan 15;148(2):612-9 [1530865] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Invited commentary: arsenic and cancer of the urinary tract. AN - 70646555; 11226972 AB - Inorganic arsenic in drinking water is a recognized cause of cancers of the skin, lung, and bladder. In the absence of an animal model for studying arsenic carcinogenesis, epidemiologic studies provide the only quantitative data for guiding risk assessment at levels that commonly occur in drinking water. To date, most estimates of risk at low and moderate levels of exposure (<200 microg/liter) have been based on extrapolation from ecologic studies of populations exposed to much higher levels. Epidemiologic data from the prospective cohort study by Chiou et al. that appears in this issue of the JOURNAL: (Am J Epidemiol 2001;153:411-18) make an important contribution to improving the precision of the estimated risk of transitional cell carcinoma of the urinary tract associated with ingested arsenic from drinking water. The great strength of the study derives from having individually based measures of exposure and cancer diagnoses. Arsenic in water is a topic of great concern and controversy, and epidemiologic studies will continue to provide crucial information about the risks of cancer and other diseases associated with ingested arsenic. JF - American journal of epidemiology AU - Cantor, K P AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, USA. cantork@exchange.nih.gov Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 422 EP - 423 VL - 153 IS - 5 SN - 0002-9262, 0002-9262 KW - Water Pollutants KW - 0 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Prospective Studies KW - Humans KW - Cohort Studies KW - Risk Assessment -- methods KW - Arsenic -- adverse effects KW - Water Pollutants -- adverse effects KW - Urinary Bladder Neoplasms -- epidemiology KW - Carcinoma, Transitional Cell -- chemically induced KW - Urinary Bladder Neoplasms -- chemically induced KW - Carcinoma, Transitional Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70646555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Invited+commentary%3A+arsenic+and+cancer+of+the+urinary+tract.&rft.au=Cantor%2C+K+P&rft.aulast=Cantor&rft.aufirst=K&rft.date=2001-03-01&rft.volume=153&rft.issue=5&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Am J Epidemiol. 2001 Mar 1;153(5):411-8 [11226969] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Helical structure of the COOH terminus of S3 and its contribution to the gating modifier toxin receptor in voltage-gated ion channels. AN - 70642790; 11222625 AB - The voltage-sensing domains in voltage-gated K(+) channels each contain four transmembrane (TM) segments, termed S1 to S4. Previous scanning mutagenesis studies suggest that S1 and S2 are amphipathic membrane spanning alpha-helices that interface directly with the lipid membrane. In contrast, the secondary structure of and/or the environments surrounding S3 and S4 are more complex. For S3, although the NH(2)-terminal part displays significant helical character in both tryptophan- and alanine-scanning mutagenesis studies, the structure of the COOH-terminal portion of this TM is less clear. The COOH terminus of S3 is particularly interesting because this is where gating modifier toxins like Hanatoxin interact with different voltage-gated ion channels. To further examine the secondary structure of the COOH terminus of S3, we lysine-scanned this region in the drk1 K(+) channel and examined the mutation-induced changes in channel gating and Hanatoxin binding affinity, looking for periodicity characteristic of an alpha-helix. Both the mutation-induced perturbation in the toxin-channel interaction and in gating support the presence of an alpha-helix of at least 10 residues in length in the COOH terminus of S3. Together with previous scanning mutagenesis studies, these results suggest that, in voltage-gated K(+) channels, the entire S3 segment is helical, but that it can be divided into two parts. The NH(2)-terminal part of S3 interfaces with both lipid and protein, whereas the COOH-terminal part interfaces with water (where Hanatoxin binds) and possibly protein. A conserved proline residue is located near the boundary between the two parts of S3, arguing for the presence of a kink in this region. Several lines of evidence suggest that these structural features of S3 probably exist in all voltage-gated ion channels. JF - The Journal of general physiology AU - Li-Smerin, Y AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 205 EP - 218 VL - 117 IS - 3 SN - 0022-1295, 0022-1295 KW - Peptides KW - 0 KW - Potassium Channels KW - hanatoxin KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Polymerase Chain Reaction KW - Protein Structure, Secondary KW - Peptides -- pharmacology KW - Fourier Analysis KW - Mutagenesis KW - Binding Sites KW - Ion Channel Gating -- physiology KW - Potassium Channels -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70642790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+physiology&rft.atitle=Helical+structure+of+the+COOH+terminus+of+S3+and+its+contribution+to+the+gating+modifier+toxin+receptor+in+voltage-gated+ion+channels.&rft.au=Li-Smerin%2C+Y%3BSwartz%2C+K+J&rft.aulast=Li-Smerin&rft.aufirst=Y&rft.date=2001-03-01&rft.volume=117&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+physiology&rft.issn=00221295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Physiol. 2000 Jan;115(1):33-50 [10613917] J Biol Chem. 1996 Jul 5;271(27):15950-62 [8663157] Nature. 1999 Dec 16;402(6763):809-13 [10617201] J Gen Physiol. 2000 Feb;115(2):193-208 [10653896] J Gen Physiol. 2000 Feb;115(2):209-22 [10653897] J Mol Biol. 2000 Mar 31;297(3):771-80 [10731427] J Gen Physiol. 2000 Jun;115(6):673-84 [10828242] Neuron. 2000 Sep;27(3):585-95 [11055440] J Gen Physiol. 2000 Nov;116(5):637-44 [11055992] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] J Mol Biol. 1984 May 5;175(1):75-81 [6427470] J Mol Biol. 1987 Jun 5;195(3):659-85 [3656427] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9012-6 [3057498] Science. 1989 Aug 4;245(4917):510-3 [2667138] Annu Rev Biochem. 1989;58:607-33 [2673018] Science. 1990 Nov 2;250(4981):646-51 [2237415] J Mol Biol. 1991 Mar 20;218(2):397-412 [2010917] Nature. 1993 Mar 11;362(6416):127-33 [7680768] Science. 1993 Jun 11;260(5114):1637-40 [8503008] Neuron. 1995 Oct;15(4):941-9 [7576642] EMBO J. 1995 Nov 1;14(21):5170-8 [7489706] Science. 1996 Jan 12;271(5246):213-6 [8539623] Neuron. 1996 Jan;16(1):113-22 [8562074] Neuron. 1996 Feb;16(2):387-97 [8789953] J Gen Physiol. 1997 Feb;109(2):191-9 [9041448] Neuron. 1997 Apr;18(4):665-73 [9136774] Neuron. 1997 Apr;18(4):675-82 [9136775] Neuron. 1997 Nov;19(5):1127-40 [9390525] Science. 1998 Apr 3;280(5360):69-77 [9525859] Science. 1998 Apr 3;280(5360):106-9 [9525854] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9 [9671721] J Gen Physiol. 1998 Oct;112(4):391-408 [9758859] Methods Enzymol. 1998;296:566-78 [9779474] J Gen Physiol. 1999 Mar;113(3):415-23 [10051517] Nat Neurosci. 1998 Dec;1(8):668-74 [10196582] J Mol Biol. 1999 Apr 23;288(1):141-5 [10329132] Q Rev Biophys. 1998 Aug;31(3):239-95 [10384687] J Gen Physiol. 2000 Jan;115(1):51-8 [10613918] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis. AN - 70640936; 11239885 AB - To describe the chronic use of high doses of intravitreal ganciclovir, in combination with foscarnet, for the treatment of cytomegalovirus retinitis. A 31-year-old man with human immunodeficiency virus (HIV) infection and unilateral active cytomegalovirus retinitis was treated with escalating intravitreal injections of ganciclovir (up to 3.0 mg twice a week) in combination with foscarnet (up to 2.4 mg twice a week) over the course of approximately 1 year. Complete regression of the retinitis was obtained with high doses of intravitreal ganciclovir and foscarnet. Visual acuity in the affected eye remained 20/20 throughout the course of therapy. No ganciclovir retinal toxicity was identified. High doses of intravitreal ganciclovir in combination with foscarnet can be well tolerated and may be required to successfully control cytomegalovirus retinitis in some patients. JF - American journal of ophthalmology AU - Velez, G AU - Roy, C E AU - Whitcup, S M AU - Chan, C C AU - Robinson, M R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. bruise-velez@erols.com Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 396 EP - 397 VL - 131 IS - 3 SN - 0002-9394, 0002-9394 KW - Antiviral Agents KW - 0 KW - Foscarnet KW - 364P9RVW4X KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Vitreous Body KW - Humans KW - Adult KW - Treatment Outcome KW - Visual Acuity KW - Male KW - Cytomegalovirus Retinitis -- drug therapy KW - Antiviral Agents -- administration & dosage KW - Ganciclovir -- administration & dosage KW - Foscarnet -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70640936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=High-dose+intravitreal+ganciclovir+and+foscarnet+for+cytomegalovirus+retinitis.&rft.au=Velez%2C+G%3BRoy%2C+C+E%3BWhitcup%2C+S+M%3BChan%2C+C+C%3BRobinson%2C+M+R&rft.aulast=Velez&rft.aufirst=G&rft.date=2001-03-01&rft.volume=131&rft.issue=3&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of two alternate vaccines based on Plasmodium falciparum merozoite surface protein 1 in an Aotus challenge trial. AN - 70635644; 11179324 AB - In an attempt to produce a more defined, clinical-grade version of a vaccine based on Plasmodium falciparum merozoite surface protein 1 (MSP1), we evaluated the efficacy of two recombinant forms of MSP1 in an Aotus nancymai challenge model system. One recombinant vaccine, bvMSP1(42), based on the 42-kDa C-terminal portion of MSP1, was expressed as a secreted protein in baculovirus-infected insect cells. A highly pure baculovirus product could be reproducibly expressed and purified at yields in excess of 8 mg of pure protein per liter of culture. This protein, when tested for efficacy in the Aotus challenge model, gave significant protection, with only one of seven monkeys requiring treatment for uncontrolled parasitemia after challenge with P. falciparum. The second recombinant protein, P30P2MSP1(19), has been used in previous studies and is based on the smaller, C-terminal 19-kDa portion of MSP1 expressed in Saccharomyces cerevisiae. Substantial changes were made in its production process to optimize expression. The optimum form of this vaccine antigen (as judged by in vitro and in vivo indicators) was then evaluated, along with bvMSP1(42), for efficacy in the A. nancymai system. The new formulation of P30P3MSP1(19) performed significantly worse than bvMSP1(42) and appeared to be less efficacious than we have found in the past, with four of seven monkeys in the vaccinated group requiring treatment for uncontrolled parasitemia. With both antigens, protection was seen only when high antibody levels were obtained by formulation of the vaccines in Freund's adjuvant. Vaccine formulation in an alternate adjuvant, MF59, resulted in significantly lower antibody titers and no protection. JF - Infection and immunity AU - Stowers, A W AU - Cioce, V AU - Shimp, R L AU - Lawson, M AU - Hui, G AU - Muratova, O AU - Kaslow, D C AU - Robinson, R AU - Long, C A AU - Miller, L H AD - Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Inc., Rockville, Maryland 20852, USA. astowers@niaid.nih.gov Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 1536 EP - 1546 VL - 69 IS - 3 SN - 0019-9567, 0019-9567 KW - Antibodies, Protozoan KW - 0 KW - Malaria Vaccines KW - Merozoite Surface Protein 1 KW - Recombinant Fusion Proteins KW - Tetanus Toxin KW - Vaccines, Synthetic KW - Index Medicus KW - Genetic Variation KW - Baculoviridae -- genetics KW - Animals KW - Technology, Pharmaceutical -- methods KW - Parasitemia KW - Antibodies, Protozoan -- blood KW - Rabbits KW - Vaccines, Synthetic -- therapeutic use KW - Aotidae KW - Tetanus Toxin -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use KW - Malaria, Falciparum -- prevention & control KW - Merozoite Surface Protein 1 -- genetics KW - Plasmodium falciparum -- immunology KW - Vaccination KW - Malaria Vaccines -- therapeutic use KW - Merozoite Surface Protein 1 -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70635644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Efficacy+of+two+alternate+vaccines+based+on+Plasmodium+falciparum+merozoite+surface+protein+1+in+an+Aotus+challenge+trial.&rft.au=Stowers%2C+A+W%3BCioce%2C+V%3BShimp%2C+R+L%3BLawson%2C+M%3BHui%2C+G%3BMuratova%2C+O%3BKaslow%2C+D+C%3BRobinson%2C+R%3BLong%2C+C+A%3BMiller%2C+L+H&rft.aulast=Stowers&rft.aufirst=A&rft.date=2001-03-01&rft.volume=69&rft.issue=3&rft.spage=1536&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell. 1999 Apr;3(4):457-64 [10230398] Gene. 1999 Apr 1;230(1):47-54 [10196473] Infect Immun. 2000 Mar;68(3):1418-27 [10678955] Infect Immun. 2000 Apr;68(4):2215-23 [10722622] Yeast. 2001 Jan 30;18(2):137-50 [11169756] J Exp Med. 1985 Jan 1;161(1):160-80 [2578540] Nature. 1985 Sep 19-25;317(6034):270-3 [2995820] Infect Immun. 1986 Apr;52(1):314-8 [3514459] J Mol Biol. 1987 May 20;195(2):273-87 [3079521] J Exp Med. 1990 Jul 1;172(1):379-82 [1694225] Infect Immun. 1991 May;59(5):1585-91 [2019429] Mol Biochem Parasitol. 1991 Nov;49(1):29-33 [1775158] Mol Biochem Parasitol. 1992 Apr;51(2):301-12 [1574088] Infect Immun. 1993 Jun;61(6):2462-7 [8363656] Mol Biochem Parasitol. 1993 May;59(1):1-14 [8515771] Mol Biochem Parasitol. 1993 May;59(1):95-100 [8515786] Mol Biochem Parasitol. 1993 Aug;60(2):303-11 [7694147] Mem Inst Oswaldo Cruz. 1992;87 Suppl 3:37-42 [1343716] Mol Biochem Parasitol. 1994 Feb;63(2):283-9 [7516493] Parasite Immunol. 1994 Feb;16(2):63-7 [8015856] J Immunol. 1994 Sep 15;153(6):2544-53 [8077664] J Immunol. 1995 Jun 1;154(11):6022-30 [7538540] J Immunol. 1995 Jul 1;155(1):236-43 [7602100] Exp Parasitol. 1995 Aug;81(1):47-54 [7628566] Mol Med. 1995 Mar;1(3):325-32 [8529111] Infect Immun. 1996 Jan;64(1):253-61 [8557348] Infect Immun. 1996 May;64(5):1502-9 [8613353] Infect Immun. 1996 Sep;64(9):3614-9 [8751907] Infect Immun. 1997 Aug;65(8):3024-31 [9234749] Infect Immun. 1997 Aug;65(8):3032-6 [9234750] J Immunol. 1997 Oct 1;159(7):3400-11 [9317139] Infect Immun. 1998 Jan;66(1):59-64 [9423839] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1715-20 [9465082] Nat Med. 1998 May;4(5 Suppl):520-4 [9585203] Mol Biochem Parasitol. 1998 May 1;92(2):241-52 [9657329] J Mol Biol. 1999 May 28;289(1):113-22 [10339410] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Ser(365)-->Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia. AN - 70633122; 11181569 AB - Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several types of human skeletal dysplasia, including the neonatally lethal dwarfism known as thanatophoric dysplasia. An engineered Ser(365)-->Cys substitution in mouse FGFR3, which is equivalent to a mutation associated with thanatophoric dysplasia-I in humans, has now been shown to cause severe dwarfism but not neonatal death. The mutant mice exhibit shortened limbs as a result of markedly reduced proliferation and impaired differentiation of growth plate chondrocytes. The receptor-activating mutation also resulted in downregulation of expression of the Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP) receptor genes, both of which are important for bone growth. Interactions between FGFR3- and PTHrP-receptor-mediated signals during endochondral ossification were examined with embryonic metatarsal bones maintained in culture under defined conditions. Consistent with the in vivo observations, FGF2 inhibited bone growth in culture and induced downregulation of IHH and PTHrP receptor gene expression. Furthermore, PTHrP partially reversed the inhibition of long bone growth caused by activation of FGFR3; however, it impaired the differentiation of chondrocytes in an FGFR3-independent manner. These observations suggest that FGFR3 and IHH-PTHrP signals are transmitted by two interacting parallel pathways that mediate both overlapping and distinct functions during endochondral ossification. JF - Human molecular genetics AU - Chen, L AU - Li, C AU - Qiao, W AU - Xu, X AU - Deng, C AD - Genetics of Development and Disease Branch, Building 10, Room 9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 457 EP - 465 VL - 10 IS - 5 SN - 0964-6906, 0964-6906 KW - DNA Primers KW - 0 KW - Hedgehog Proteins KW - Parathyroid Hormone-Related Protein KW - Proteins KW - Receptors, Fibroblast Growth Factor KW - Trans-Activators KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Serine KW - 452VLY9402 KW - Fgfr3 protein, mouse KW - EC 2.7.10.1 KW - Protein-Tyrosine Kinases KW - Receptor, Fibroblast Growth Factor, Type 3 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Fibroblast Growth Factor 2 -- pharmacology KW - Animals KW - Cell Differentiation KW - Mice KW - Mutagenesis, Site-Directed KW - Base Sequence KW - In Situ Hybridization KW - Chondrocytes -- cytology KW - Growth Plate -- anatomy & histology KW - Gene Expression Regulation -- drug effects KW - Cell Division KW - Receptors, Fibroblast Growth Factor -- physiology KW - Receptors, Fibroblast Growth Factor -- chemistry KW - Down-Regulation KW - Cysteine -- genetics KW - Signal Transduction -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Achondroplasia -- genetics KW - Serine -- genetics KW - Receptors, Fibroblast Growth Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70633122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=A+Ser%28365%29--%26gt%3BCys+mutation+of+fibroblast+growth+factor+receptor+3+in+mouse+downregulates+Ihh%2FPTHrP+signals+and+causes+severe+achondroplasia.&rft.au=Chen%2C+L%3BLi%2C+C%3BQiao%2C+W%3BXu%2C+X%3BDeng%2C+C&rft.aulast=Chen&rft.aufirst=L&rft.date=2001-03-01&rft.volume=10&rft.issue=5&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-14 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. AN - 70629367; 11179329 AB - To investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR in Ascaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2; P = 0.02) and gamma interferon (IFN-gamma; P = 0.001) in the three study groups combined; however, postvaccination increases in IFN-gamma were significant only in the albendazole-treated A. lumbricoides infection group (P = 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P = 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-gamma) to CT-B, that infection with A. lumbricoides diminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas. JF - Infection and immunity AU - Cooper, P J AU - Chico, M AU - Sandoval, C AU - Espinel, I AU - Guevara, A AU - Levine, M M AU - Griffin, G E AU - Nutman, T B AD - Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. pc102d@hotmail.com Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 1574 EP - 1580 VL - 69 IS - 3 SN - 0019-9567, 0019-9567 KW - Anthelmintics KW - 0 KW - Antigens, Helminth KW - Cholera Vaccines KW - Interleukin-2 KW - cholera vaccine CVD 103-HgR KW - Interferon-gamma KW - 82115-62-6 KW - Cholera Toxin KW - 9012-63-9 KW - Albendazole KW - F4216019LN KW - Index Medicus KW - Animals KW - Double-Blind Method KW - Humans KW - Adult KW - Leukocytes, Mononuclear -- immunology KW - Interferon-gamma -- blood KW - Vaccination KW - Anthelmintics -- therapeutic use KW - Albendazole -- therapeutic use KW - Male KW - Female KW - Antigens, Helminth -- immunology KW - Interleukin-2 -- blood KW - Cholera Toxin -- immunology KW - Cholera Vaccines -- immunology KW - Ascariasis -- drug therapy KW - Ascariasis -- immunology KW - Cholera Vaccines -- therapeutic use KW - Cholera -- prevention & control KW - Ascaris lumbricoides -- immunology KW - Ascaris lumbricoides -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70629367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Human+infection+with+Ascaris+lumbricoides+is+associated+with+suppression+of+the+interleukin-2+response+to+recombinant+cholera+toxin+B+subunit+following+vaccination+with+the+live+oral+cholera+vaccine+CVD+103-HgR.&rft.au=Cooper%2C+P+J%3BChico%2C+M%3BSandoval%2C+C%3BEspinel%2C+I%3BGuevara%2C+A%3BLevine%2C+M+M%3BGriffin%2C+G+E%3BNutman%2C+T+B&rft.aulast=Cooper&rft.aufirst=P&rft.date=2001-03-01&rft.volume=69&rft.issue=3&rft.spage=1574&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Bull World Health Organ. 1996;74(5):491-500 [9002329] J Infect Dis. 1996 Jan;173(1):269-72 [8537675] J Infect Dis. 1998 Oct;178(4):1133-8 [9806045] J Infect Dis. 1999 Mar;179(3):738-42 [9952390] Immunol Today. 1999 Feb;20(2):95-101 [10098329] J Infect Dis. 1999 Nov;180(5):1709-12 [10515838] J Infect Dis. 2000 Oct;182(4):1199-206 [10979918] J Infect Dis. 2000 Oct;182(4):1207-13 [10979919] Am J Epidemiol. 1972 Oct;96(4):263-9 [4342327] Am J Clin Nutr. 1972 Nov;25(11):1276-81 [5086050] J Infect Dis. 1986 Jun;153(6):1126-31 [3701119] J Clin Invest. 1991 Jul;88(1):143-8 [1905327] Eur J Immunol. 1991 Oct;21(10):2333-9 [1833201] Southeast Asian J Trop Med Public Health. 1991 Mar;22(1):84-7 [1948266] Rev Infect Dis. 1991 Sep-Oct;13(5):926-39 [1660184] J Immunol. 1992 May 15;148(10):3264-70 [1533656] J Infect Dis. 1992 Jun;165(6):1042-8 [1583321] J Immunol. 1992 Jun 1;148(11):3567-71 [1350292] Lancet. 1992 Sep 19;340(8821):689-94 [1355798] Infect Immun. 1993 Feb;61(2):729-33 [8423098] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):948-52 [8094248] Vaccine. 1993;11(2):119-21 [8438610] Eur J Immunol. 1993 Sep;23(9):2136-43 [8370397] J Exp Med. 1993 Oct 1;178(4):1309-20 [8376936] J Immunol. 1993 Nov 1;151(9):4857-64 [8409444] Vaccine. 1994 Jan;12(1):65-72 [8303943] Parasitology. 1993;107 Suppl:S125-36 [8115177] Clin Exp Immunol. 1994 May;96(2):238-44 [8187332] J Infect Dis. 1994 Oct;170(4):962-70 [7930742] Trans R Soc Trop Med Hyg. 1994 May-Jun;88(3):259-61 [7974657] Vaccine. 1994 Aug;12(10):903-11 [7975832] Parasitology. 1995 Jan;110 ( Pt 1):103-11 [7845707] J Infect Dis. 1995 Mar;171(3):659-71 [7876613] Am J Respir Crit Care Med. 1997 Jul;156(1):50-4 [9230725] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dolastatin 11, a marine depsipeptide, arrests cells at cytokinesis and induces hyperpolymerization of purified actin. AN - 70627672; 11179440 AB - The successful synthesis of dolastatin 11, a depsipeptide originally isolated from the mollusk Dolabella auricularia, permitted us to study its effects on cells. The compound arrested cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network. In a dose-and time-dependent manner, F-actin was rearranged into aggregates, and subsequently the cells displayed dramatic cytoplasmic retraction. The effects of dolastatin 11 were most similar to those of the sponge-derived depsipeptide jasplakinolide, but dolastatin 11 was about 3-fold more cytotoxic than jasplakinolide in the cells studied. Like jasplakinolide, dolastatin 11 induced the hyperassembly of purified actin into filaments of apparently normal morphology. Dolastatin 11 was qualitatively more active than jasplakinolide and, in a quantitative assay we developed, dolastatin 11 was twice as active as jasplakinolide and 4-fold more active than phalloidin. However, in contrast to jasplakinolide and phalloidin, dolastatin 11 did not inhibit the binding of a fluorescent phalloidin derivative to actin polymer nor was it able to displace the phalloidin derivative from polymer. Thus, despite its structural similarity to other agents that induce actin assembly (all are peptides or depsipeptides), dolastatin 11 may interact with actin polymers at a distinct drug binding site. JF - Molecular pharmacology AU - Bai, R AU - Verdier-Pinard, P AU - Gangwar, S AU - Stessman, C C AU - McClure, K J AU - Sausville, E A AU - Pettit, G R AU - Bates, R B AU - Hamel, E AD - Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 462 EP - 469 VL - 59 IS - 3 SN - 0026-895X, 0026-895X KW - Actins KW - 0 KW - Antineoplastic Agents KW - Bacterial Proteins KW - Depsipeptides KW - Fluorescent Dyes KW - Isothiocyanates KW - Oligopeptides KW - Peptides KW - Peptides, Cyclic KW - chondramide D KW - dolastatin 11 KW - jasplakinolide KW - 102396-24-7 KW - Phalloidine KW - 17466-45-4 KW - isothiocyanic acid KW - 3129-90-6 KW - Index Medicus KW - Peptides -- chemical synthesis KW - Animals KW - Isothiocyanates -- metabolism KW - Fluorescent Dyes -- metabolism KW - Cells, Cultured KW - Dipodomys KW - Phalloidine -- pharmacology KW - Cell Division -- drug effects KW - Peptides -- chemistry KW - Peptides -- pharmacology KW - Actins -- ultrastructure KW - Oligopeptides -- chemistry KW - Actins -- drug effects KW - Actins -- immunology KW - Actins -- metabolism KW - Actin Cytoskeleton -- drug effects KW - Oligopeptides -- chemical synthesis KW - Oligopeptides -- pharmacology KW - Peptides, Cyclic -- chemical synthesis KW - Peptides, Cyclic -- chemistry KW - Peptides, Cyclic -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70627672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Dolastatin+11%2C+a+marine+depsipeptide%2C+arrests+cells+at+cytokinesis+and+induces+hyperpolymerization+of+purified+actin.&rft.au=Bai%2C+R%3BVerdier-Pinard%2C+P%3BGangwar%2C+S%3BStessman%2C+C+C%3BMcClure%2C+K+J%3BSausville%2C+E+A%3BPettit%2C+G+R%3BBates%2C+R+B%3BHamel%2C+E&rft.aulast=Bai&rft.aufirst=R&rft.date=2001-03-01&rft.volume=59&rft.issue=3&rft.spage=462&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. AN - 70624241; 11170730 AB - Convection-enhanced delivery (CED) distributes macromolecules in the brain in a homogeneous, targeted fashion in clinically useful volumes. However, the binding of growth factors to heparin-binding sites in the extracellular matrix may limit the volume of distribution (V(d)). To overcome this limitation, we examined the effects of heparin coinfusion on V(d) of glial-derived neurotrophic factor (GDNF), neurturin (NTN), artemin, and a nonspecifically bound protein, albumin. Heparin coinfusion significantly enhanced the V(d) of GDNF and GDNF-homologous trophic factors, probably by binding and blocking heparin-binding sites in the extracellular matrix. Furthermore, coinfusion of heparin with NTN enhanced striatal dopamine metabolism, compared to trophic factor administered alone. The negligible benefit of GDNF in recent clinical trials of Parkinson's disease may result from limited tissue distribution. Heparin coinfusion during CED targeting the striatum may alleviate this important limitation. This study demonstrates the influence of receptor binding on the distribution of trophic factors in the CNS. Copyright 2001 Academic Press. JF - Experimental neurology AU - Hamilton, J F AU - Morrison, P F AU - Chen, M Y AU - Harvey-White, J AU - Pernaute, R S AU - Phillips, H AU - Oldfield, E AU - Bankiewicz, K S AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 155 EP - 161 VL - 168 IS - 1 SN - 0014-4886, 0014-4886 KW - Artn protein, rat KW - 0 KW - Gdnf protein, rat KW - Glial Cell Line-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neurturin KW - Nrtn protein, rat KW - Serum Albumin, Bovine KW - Heparin KW - 9005-49-6 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Models, Animal KW - Animals KW - Rats, Sprague-Dawley KW - Serum Albumin, Bovine -- pharmacokinetics KW - Parkinson Disease KW - Drug Synergism KW - Infusions, Parenteral KW - Immunohistochemistry KW - Heparin -- administration & dosage KW - Nerve Growth Factors -- pharmacology KW - Heparin -- pharmacology KW - Corpus Striatum -- metabolism KW - Brain -- drug effects KW - Nerve Tissue Proteins -- pharmacokinetics KW - Dopamine -- metabolism KW - Corpus Striatum -- drug effects KW - Nerve Tissue Proteins -- administration & dosage KW - Brain -- metabolism KW - Nerve Growth Factors -- pharmacokinetics KW - Nerve Growth Factors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70624241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Heparin+coinfusion+during+convection-enhanced+delivery+%28CED%29+increases+the+distribution+of+the+glial-derived+neurotrophic+factor+%28GDNF%29+ligand+family+in+rat+striatum+and+enhances+the+pharmacological+activity+of+neurturin.&rft.au=Hamilton%2C+J+F%3BMorrison%2C+P+F%3BChen%2C+M+Y%3BHarvey-White%2C+J%3BPernaute%2C+R+S%3BPhillips%2C+H%3BOldfield%2C+E%3BBankiewicz%2C+K+S&rft.aulast=Hamilton&rft.aufirst=J&rft.date=2001-03-01&rft.volume=168&rft.issue=1&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia. AN - 70585877; 11181372 AB - The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (P or =6 mg/kg/day per os generated sustained concentrations in plasma of > or =1 microg/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at > or =6 mg/kg/day per os in persistently neutropenic rabbits. JF - Antimicrobial agents and chemotherapy AU - Petraitiene, R AU - Petraitis, V AU - Groll, A H AU - Sein, T AU - Piscitelli, S AU - Candelario, M AU - Field-Ridley, A AU - Avila, N AU - Bacher, J AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 857 EP - 869 VL - 45 IS - 3 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Mannans KW - Triazoles KW - galactomannan KW - 11078-30-1 KW - Itraconazole KW - 304NUG5GF4 KW - posaconazole KW - 6TK1G07BHZ KW - Index Medicus KW - Itraconazole -- pharmacokinetics KW - Animals KW - Itraconazole -- therapeutic use KW - Neutropenia -- etiology KW - Treatment Outcome KW - Itraconazole -- adverse effects KW - Disease Models, Animal KW - Rabbits KW - Aspergillus fumigatus -- drug effects KW - Antibiotic Prophylaxis KW - Female KW - Aspergillosis -- metabolism KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacokinetics KW - Lung Diseases, Fungal -- drug therapy KW - Aspergillosis -- drug therapy KW - Triazoles -- adverse effects KW - Mannans -- metabolism KW - Mannans -- immunology KW - Triazoles -- pharmacokinetics KW - Antifungal Agents -- therapeutic use KW - Aspergillosis -- immunology KW - Lung Diseases, Fungal -- immunology KW - Lung Diseases, Fungal -- prevention & control KW - Aspergillosis -- prevention & control KW - Lung Diseases, Fungal -- metabolism KW - Triazoles -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70585877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Antifungal+activity+and+pharmacokinetics+of+posaconazole+%28SCH+56592%29+in+treatment+and+prevention+of+experimental+invasive+pulmonary+aspergillosis%3A+correlation+with+galactomannan+antigenemia.&rft.au=Petraitiene%2C+R%3BPetraitis%2C+V%3BGroll%2C+A+H%3BSein%2C+T%3BPiscitelli%2C+S%3BCandelario%2C+M%3BField-Ridley%2C+A%3BAvila%2C+N%3BBacher%2C+J%3BWalsh%2C+T+J&rft.aulast=Petraitiene&rft.aufirst=R&rft.date=2001-03-01&rft.volume=45&rft.issue=3&rft.spage=857&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer. 1992 Jun 1;69(11):2653-62 [1315207] Clin Infect Dis. 1992 Mar;14 Suppl 1:S43-53 [1562695] Antimicrob Agents Chemother. 1994 Mar;38(3):518-22 [8203848] Antimicrob Agents Chemother. 1994 Jun;38(6):1303-8 [8092829] Bone Marrow Transplant. 1994;14 Suppl 5:S1-2 [7703924] J Clin Microbiol. 1995 Feb;33(2):497-500 [7714217] Antimicrob Agents Chemother. 1995 May;39(5):1065-9 [7625790] J Clin Microbiol. 1995 Jul;33(7):1912-4 [7665670] Antimicrob Agents Chemother. 1996 May;40(5):1314-6 [8723494] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] Antimicrob Agents Chemother. 1996 Aug;40(8):1910-3 [8843302] Pediatr Infect Dis J. 1996 Mar;15(3):232-7 [8852911] J Clin Microbiol. 1997 Jan;35(1):139-43 [8968895] Antimicrob Agents Chemother. 1997 Jan;41(1):180-3 [8980776] J Clin Oncol. 1997 Jan;15(1):139-47 [8996135] Antimicrob Agents Chemother. 1997 Feb;41(2):233-5 [9021172] Antimicrob Agents Chemother. 1997 May;41(5):1124-6 [9145880] Antimicrob Agents Chemother. 1997 Jul;41(7):1504-7 [9210674] Antimicrob Agents Chemother. 1997 Jul;41(7):1558-61 [9210684] Antimicrob Agents Chemother. 1997 Oct;41(10):2310-1 [9333073] J Pharm Biomed Anal. 1998 Feb;16(6):1005-12 [9547703] Adv Pharmacol. 1998;44:343-500 [9547888] Curr Opin Chem Biol. 1997 Aug;1(2):176-82 [9667858] Mycoses. 1998;41 Suppl 1:32-8 [9717384] J Clin Microbiol. 1998 Oct;36(10):2950-6 [9738049] Mycopathologia. 1998;141(2):73-7 [9750338] J Antimicrob Chemother. 1998 Oct;42(4):539-42 [9818757] Antimicrob Agents Chemother. 1998 Dec;42(12):3242-4 [9835520] Clin Microbiol Rev. 1999 Jan;12(1):40-79 [9880474] Antimicrob Agents Chemother. 1999 Feb;43(2):322-8 [9925526] Antimicrob Agents Chemother. 1999 Mar;43(3):589-91 [10049271] J Clin Microbiol. 1999 Oct;37(10):3223-8 [10488181] Mycoses. 1999;42(7-8):431-42 [10546484] J Antimicrob Chemother. 1999 Dec;44(6):827-9 [10590286] Antimicrob Agents Chemother. 2000 Jan;44(1):226-9 [10602757] J Chemother. 1999 Dec;11(6):504-12 [10678792] Antimicrob Agents Chemother. 2000 Mar;44(3):727-31 [10681346] Antimicrob Agents Chemother. 2000 Mar;44(3):780-2 [10681359] Antimicrob Agents Chemother. 2000 May;44(5):1159-62 [10770745] J Chromatogr B Biomed Sci Appl. 2000 Jan 28;738(1):93-8 [10778930] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] Radiology. 1985 Dec;157(3):611-4 [3864189] J Comput Assist Tomogr. 1987 May-Jun;11(3):534-6 [3571603] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Rev Infect Dis. 1990 Mar-Apr;12(2):308-29 [2184499] Postgrad Med. 1990 Jul;88(1):151-2, 155-61, 165-6 [2195479] J Infect Dis. 1994 Feb;169(2):356-68 [8106769] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity of Antiosteosarcoma Recombinant Immunotoxins Composed of TP-3 Fv Fragments and a Truncated Pseudomonas Exotoxin A. AN - 1859352044; 11449071 AB - SUMMARY: Regrowth of drug-resistant tumor cells is responsible for approximately half of an unselected osteosarcoma population still dying of the disease despite aggressive combination therapy. Two monoclonal antibodies, TP-1 (immunoglobulin 2a) and TP-3 (immunoglobulin 2b) are available, which specifically recognize an antigen on osteosarcoma cells. In this work, we have fused the variable (V) genes of TP-3 to a truncated fragment of Pseudomonas exotoxin A, referred to as PE38. Two immunotoxins were made that differed in the Fv portion: TP-3(scFv)-PE38, which contains a peptide linker, and TP-3(dsFv)-PE38, which contains a disulfide bond for stabilization of the association between the V domains. Recombinant TP-3 immunotoxins were expressed in Escherichia coli and purified from inclusion bodies. We describe the design and expression of these immunotoxins, and their properties with regard to antigen binding, stability, and cytotoxicity. Toxicity studies were done in mice. We found that the immunotoxins exhibited very similar in vitro properties, whereas in vivo TP-3(dsFv)-PE38 was much better tolerated than TP-3(scFv)-PE38. JF - Journal of immunotherapy : official journal of the Society for Biological Therapy AU - Onda, Masanori AU - Olafsen, Tove AU - Tsutsumi, Yasuo AU - Bruland ØS, Øyvind S. AU - Pastan, Ira AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, U.S.A.; and Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway. Y1 - 2001/03// PY - 2001 DA - March 2001 SP - 144 EP - 150 VL - 24 IS - 2 SN - 1053-8550, 1053-8550 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859352044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=Cytotoxicity+of+Antiosteosarcoma+Recombinant+Immunotoxins+Composed+of+TP-3+Fv+Fragments+and+a+Truncated+Pseudomonas+Exotoxin+A.&rft.au=Onda%2C+Masanori%3BOlafsen%2C+Tove%3BTsutsumi%2C+Yasuo%3BBruland+%C3%98S%2C+%C3%98yvind+S.%3BPastan%2C+Ira&rft.aulast=Onda&rft.aufirst=Masanori&rft.date=2001-03-01&rft.volume=24&rft.issue=2&rft.spage=144&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid detection of mutations in the human-derived Pneumocystis carinii dihydropteroate synthase gene associated with sulfa resistance AN - 18073075; 4884359 AB - Recent studies have shown that point mutations in the dihydropteroate synthase (DHPS) gene of human-derived Pneumocystis carinii are related to exposure to sulfa drugs and possibly represent the emergence of sulfa resistance. We developed a simple single-strand conformation polymorphism (SSCP) method to permit rapid detection of these mutations. With plasmid constructs, SSCP was able to detect as little as 10% of a minority population. The SSCP assay was compared to direct sequencing for typing the DHPS gene by examining 37 clinical isolates with known DHPS sequences and 41 clinical isolates with unknown DHPS sequences. The typing results were consistent between these two methods for all isolates except 11 in which mutations were detected by SSCP but not by direct sequencing. Sequencing of individual clones after subcloning confirmed the presence of mutations in a minority population as determined by SSCP. SSCP is a very simple and sensitive method for rapid identification of P. camii DHPS mutations. JF - Antimicrobial Agents & Chemotherapy AU - Ma, L AU - Kovacs, JA AD - Building 10, Room 7D43, National Institutes of Health, 10 Center Dr. MSC 1662, Bethesda, MD 20892-1662, USA, jkovacs@nih.gov. Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 776 EP - 780 VL - 45 IS - 3 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Electrophoresis KW - Pneumocystis carinii KW - Drug resistance KW - Polymorphism KW - Point mutation KW - Plasmids KW - Dihydropteroate synthase KW - Polymerase chain reaction KW - Sulfonamides KW - K 03079:Fungi KW - A 01117:Fungi KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18073075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Rapid+detection+of+mutations+in+the+human-derived+Pneumocystis+carinii+dihydropteroate+synthase+gene+associated+with+sulfa+resistance&rft.au=Ma%2C+L%3BKovacs%2C+JA&rft.aulast=Ma&rft.aufirst=L&rft.date=2001-03-01&rft.volume=45&rft.issue=3&rft.spage=776&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pneumocystis carinii; Drug resistance; Sulfonamides; Dihydropteroate synthase; Point mutation; Plasmids; Electrophoresis; Polymerase chain reaction; Polymorphism ER - TY - JOUR T1 - Toxicology and Carcinogenesis Studies of p,p'-Dichlorodiphenyl Sulfone in Rats and Mice AN - 17880986; 5113915 AB - p,p'-Dichlorodiphenyl sulfone (DDS) is used as a starting material in the production of polysulfones and polyethersufones, a family of thermoplastics. DDS was studied because of its high production volume and use. In toxicology studies, 10 Fischer 344 rats and 10 B6C3F1 mice/sex/group were fed diets containing 0, 30, 100, 300, 1,000 or 3,000 ppm DDS for 14 weeks. All animals survived until the end of the studies. Mean body weights of groups exposed to 300 ppm or greater were significantly decreased. Liver and kidney in rats and liver in mice were the major target organs of DDS toxicity. Dose-related increases in liver weights and incidences of centrilobular hepatocyte hypertrophy were observed in DDS-exposed groups. Nephropathy was seen in male and female rats only at and above 300 ppm. Neurotoxicity evaluations were negative in DDS-treated animals. Clinical chemistry and hematology parameters were minimally affected. In the 2-year toxicity and carcinogenicity studies, 50 rats and 50 mice/sex/group were fed diets containing 0, 10 (male rats), 30, 100, or 300 ppm DDS for 104 to 105 weeks. Survival of exposed groups was not affected. There were no clinical signs of toxicity related to DDS exposure. Final mean body weights were 2-17% lower in DDS-treated groups. Liver was the only target organ of DDS-induced toxicity. The incidence of centrilobular hepatocyte hypertrophy in mice and rats, and the incidence of bile duct hyperplasia and centrilobular degeneration in female rats was significantly greater than in controls. A no-observed-adverse-effect level (NOAEL) of 30 ppm DDS in the diet (1.5 mg/kg body weight) was established for rats. DDS was not carcinogenic in these studies. JF - Toxicological Sciences AU - Chhabra, R S AU - Herbert, R A AU - Bucher, J R AU - Travlos, G S AU - Johnson, J D AU - Hejtmancik, M R AD - National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 28 EP - 37 VL - 60 IS - 1 SN - 1096-6080, 1096-6080 KW - rats KW - mice KW - Dichlorodiphenyl sulfone KW - Toxicology Abstracts KW - Body weight KW - Carcinogenesis KW - Kidney KW - Liver KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17880986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Toxicology+and+Carcinogenesis+Studies+of+p%2Cp%27-Dichlorodiphenyl+Sulfone+in+Rats+and+Mice&rft.au=Chhabra%2C+R+S%3BHerbert%2C+R+A%3BBucher%2C+J+R%3BTravlos%2C+G+S%3BJohnson%2C+J+D%3BHejtmancik%2C+M+R&rft.aulast=Chhabra&rft.aufirst=R&rft.date=2001-03-01&rft.volume=60&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Body weight; Liver; Kidney; Carcinogenesis ER - TY - JOUR T1 - Sawmill Chemicals and Carcinogenesis AN - 17880982; 5122185 AB - Workers in wood industries are exposed to variable medleys of chemicals, both natural and synthetic. Additional exposures include fungi, bacteria, bark and wood dusts, solvents, paints, and various other wood coatings. These individual and conglomerate exposures have been associated with diverse occupational illnesses and hazards, including cancers. In this commentary, I summarize both experimental and epidemiologic carcinogenesis results for several chemicals used in the wood industry, as well as for wood dust. Working in the wood industries entails excess risks of cancers, among other diseases and workplace injuries. A key to preventing occupationally and environmentally associated cancers, as in the wood industries, is avoiding exposures to chemicals and wood dusts and, in particular, chemicals known to cause cancer in animals or/and humans. JF - Environmental Health Perspectives AU - Huff, J AD - NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA, huff1@niehs.nih.gov Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 209 EP - 212 VL - 109 IS - 3 SN - 0091-6765, 0091-6765 KW - man KW - sawmills KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Chemicals KW - Bacteria KW - Fungi KW - Lumber industry KW - Solvents KW - Xenobiotics KW - Dust KW - Reviews KW - Carcinogenesis KW - Chemical pollution KW - Occupational exposure KW - X 24250:Reviews KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17880982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Sawmill+Chemicals+and+Carcinogenesis&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=2001-03-01&rft.volume=109&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lumber industry; Occupational exposure; Carcinogenesis; Dust; Fungi; Solvents; Bacteria; Chemicals; Reviews; Xenobiotics; Chemical pollution ER - TY - JOUR T1 - Regulation of RpoS by a novel small RNA: the characterization of RprA AN - 17870437; 5116009 AB - Translational regulation of the stationary phase sigma factor RpoS is mediated by the formation of a double-stranded RNA stem-loop structure in the upstream region of the rpoS messenger RNA, occluding the translation initiation site. The interaction of the rpoS mRNA with a small RNA, DsrA, disrupts the double-strand pairing and allows high levels of translation initiation. We screened a multicopy library of Escherichia coli DNA fragments for novel activators of RpoS translation when DsrA is absent. Clones carrying rprA (oS egulator RNA) increased the translation of RpoS. The rprA gene encodes a 106 nucleotide regulatory RNA. As with DsrA, RprA is predicted to form three stem-loops and is highly conserved in Salmonella and Klebsiella species. Thus, at least two small RNAs, DsrA and RprA, participate in the positive regulation of RpoS translation. Unlike DsrA, RprA does not have an extensive region of complementarity to the RpoS leader, leaving its mechanism of action unclear. RprA is non-essential. Mutations in the gene interfere with the induction of RpoS after osmotic shock when DsrA is absent, demonstrating a physiological role for RprA. The existence of two very different small RNA regulators of RpoS translation suggests that such additional regulatory RNAs are likely to exist, both for regulation of RpoS and for regulation of other important cellular components. JF - Molecular Microbiology AU - Majdalani, N AU - Chen, S AU - Murrow, J AU - St John, K AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bldg. 37 Room 2E 18, Bethesda, MD 20892-4255, USA. Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 1382 EP - 1394 PB - Blackwell Science Ltd VL - 39 IS - 5 SN - 0950-382X, 0950-382X KW - DsrA RNA KW - RprA protein KW - rpoS gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Translation initiation KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17870437?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Regulation+of+RpoS+by+a+novel+small+RNA%3A+the+characterization+of+RprA&rft.au=Majdalani%2C+N%3BChen%2C+S%3BMurrow%2C+J%3BSt+John%2C+K%3BGottesman%2C+S&rft.aulast=Majdalani&rft.aufirst=N&rft.date=2001-03-01&rft.volume=39&rft.issue=5&rft.spage=1382&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Translation initiation ER - TY - JOUR T1 - Murine model for lymphocytic tropism by Borrelia burgdorferi AN - 17857527; 4884586 AB - In vitro studies have demonstrated direct interactions between Borrelia burgdorferi and human B and T cells. However, largely because disseminated infections typically occur at very low density, little is known about associations between spirochetes and mammalian host cells in vivo. To assess whether spirochetes interact directly with lymphocytes in mammals, we developed a mouse model for lymphotropism. By repeatedly coincubating spirochetes with primary mouse lymphocytes that were immobilized by adherence to immunomagnetic beads, we were able to preferentially enrich cultures for or against bacteria with constitutive affinity for murine B and T cells. Populations of lymphotropically enriched, stock infectious, and lymphotropically depleted spirochetes were injected intradermally into mice. Lymphocytes were then purified from the blood and spleens of challenged mice and placed into spirochetal culture medium. Cultures of B. burgdorferi were obtained from primary lymphocyte preparations from mice challenged with each of the three populations of spirochetes. Recovery of lymphocyte-associated bacteria occurred within 1 h of challenge with enriched bacteria. Lymphocyte preparations from mice challenged with stock infectious and lymphotropically depleted bacteria produced cultures after 1 day postchallenge. All lymphocyte preparations were culture negative after 1 week. These results demonstrate that lymphotropic B. burgdorferi is infectious in mice and suggest that associations between spirochetes and lymphocytes occur in vivo. The results also suggest that factors involved in lymphocytic binding may be inducible in vivo. Thus, this system provides a model for studying the role of such interactions in mammalian infections. JF - Infection and Immunity AU - Dorward, D W AU - Larson, R S AD - NIH/Rocky Mountain Laboratories, 903 South Fourth St., Hamilton, MT 59840, USA, dave_dorward@nih.gov Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 1428 EP - 1432 VL - 69 IS - 3 SN - 0019-9567, 0019-9567 KW - Microbiology Abstracts B: Bacteriology KW - Lymphocytes B KW - Borrelia burgdorferi KW - Lymphocytes T KW - Animal models KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17857527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Murine+model+for+lymphocytic+tropism+by+Borrelia+burgdorferi&rft.au=Dorward%2C+D+W%3BLarson%2C+R+S&rft.aulast=Dorward&rft.aufirst=D&rft.date=2001-03-01&rft.volume=69&rft.issue=3&rft.spage=1428&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Animal models; Lymphocytes B; Lymphocytes T ER - TY - JOUR T1 - Functional characteristics of a protective monoclonal antibody against serotype A and C lipooligosaccharides from Moraxella catarrhalis AN - 17855243; 4884577 AB - A monoclonal antibody (MAb), designated MAb 8E7 (immunoglobulin G3), specific for Moraxella catarrhalis lipooligosaccharide (LOS) was evaluated for its functional activity in vitro and in a mouse model of colonization. Enzyme-linked immunosorbent assay (ELISA) demonstrated that the MAb 8E7 could be prepared to a high titer against LOS of the homologous strain O35E, and that it had bactericidal activity. MAb 8E7 reacted with M. catarrhalis serotype A and C LOSs but not serotype B LOS, as measured by ELISA and Western blotting. On the basis of published structures of LOSs, this suggests that the epitope recognized by MAb 8E7 is directed to a common sequence of either alpha -GlcNAc-(1 arrow right 2)- beta -Glc-(1 arrow right at the branch substituting position 4 of the trisubstituted Glc residue or a terminal tetrasaccharide alpha -Gal-(1 arrow right 4)- beta -Gal-(1 arrow right 4)- alpha -Glc-(1 arrow right 2)- beta -Glc-(1 arrow right at the branch substituting position 6 of the trisubstituted Glc residue. In a whole-cell ELISA, MAb 8E7 reacted with 70% of the 30 wild-type strains and clinical isolates tested. Immunoelectron microscopy demonstrated that MAb 8E7 reacted with a cell surface-exposed epitope of LOS on strain O35E. MAb 8E7 inhibited the adherence of strain O35E to Chang conjunctival epithelial cells by 90%. Passive immunization with MAb 8E7 could significantly enhance the clearance of strain O35E from mouse lungs in an aerosol challenge mouse model. This enhanced bacterial clearance was inhibited when MAb 8E7 was absorbed by M. catarrhalis serotype A LOS, indicating that the M. catarrhalis LOS-directed antibody may play a major role in the enhancement of M. catarrhalis clearance from lungs. These data suggest that MAb 8E7, which recognizes surface-exposed LOS of M. catarrhalis, is a protective antibody against M. catarrhalis. JF - Infection and Immunity AU - Hu, W-G AU - Chen, J AU - McMichael, J C AU - Gu, X-X AD - 5 Research Ct., Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 1358 EP - 1363 VL - 69 IS - 3 SN - 0019-9567, 0019-9567 KW - mice KW - Lipooligosaccharides KW - Moraxella catarrhalis KW - lipooligosaccharides KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Western blotting KW - Enzyme-linked immunosorbent assay KW - Monoclonal antibodies KW - Bactericides KW - Animal models KW - Immunization (passive) KW - Epitopes KW - J 02834:Vaccination and immunization KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17855243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Functional+characteristics+of+a+protective+monoclonal+antibody+against+serotype+A+and+C+lipooligosaccharides+from+Moraxella+catarrhalis&rft.au=Hu%2C+W-G%3BChen%2C+J%3BMcMichael%2C+J+C%3BGu%2C+X-X&rft.aulast=Hu&rft.aufirst=W-G&rft.date=2001-03-01&rft.volume=69&rft.issue=3&rft.spage=1358&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Moraxella catarrhalis; Monoclonal antibodies; Enzyme-linked immunosorbent assay; Western blotting; Animal models; Bactericides; Epitopes; Immunization (passive) ER - TY - JOUR T1 - Primate colour predicts social status and aggressive outcome AN - 17850652; 4873658 AB - Colourful signals in insects, fish, amphibians, lizards and birds have attracted considerable attention among evolutionary biologists. While primates display the most conspicuous secondary sexual coloration in mammals, little is known about its function. In several types of organisms, variation in colour predicts differences in social status. For this study, I experimentally investigated the relationship between scrotal colour and social status in adult vervet monkeys Cercopithecus aethiops sabaeus, by analysing the social interactions between pairs of unfamiliar males matched for size, but differing in scrotal colour. Differences in scrotal colour predicted eventual social status, as males with a dark scrotum dominated those with a pale scrotum. Experimental modification of scrotal colour failed to confirm that scrotal colour alone signalled social status, but supported the finding that males with scrota of similar colour were more antagonistic towards each other than males differing in colour. These results represent the first experimental evidence for a relationship between colour and social status in primates. Copyright 2001 The Association for the Study of Animal Behaviour JF - Animal Behaviour AU - Gerald AD - Department of Anthropology, University of California, Los Angeles, geraldme@mail.nih.gov Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 559 EP - 566 PB - Academic Press VL - 61 IS - 3 SN - 0003-3472, 0003-3472 KW - Males KW - Animal Behavior Abstracts; Ecology Abstracts KW - Coloration KW - Cercopithecus aethiops sabaeus KW - Aggression KW - Social rank KW - D 04672:Mammals KW - Y 25398:Primates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17850652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Animal+Behaviour&rft.atitle=Primate+colour+predicts+social+status+and+aggressive+outcome&rft.au=Gerald&rft.aulast=Gerald&rft.aufirst=&rft.date=2001-03-01&rft.volume=61&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Animal+Behaviour&rft.issn=00033472&rft_id=info:doi/10.1006%2Fanbe.2000.1648 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cercopithecus aethiops sabaeus; Coloration; Aggression; Social rank DO - http://dx.doi.org/10.1006/anbe.2000.1648 ER - TY - JOUR T1 - Identification and characterization of a second extracellular collagen-like protein made by group A Streptococcus: control of production at the level of translation AN - 17848059; 4884625 AB - A recent study found that group A Streptococcus (GAS) expresses a cell surface protein with similarity to human collagen (S. Lukomski, K. Nakashima, I. Abdi, V. J. Cipriano, R. M. Ireland, S. R. Reid, G. G. Adams, and J. M. Musser, Infect. Immun. 68:6542-6553, 2000). This streptococcal collagen-like protein (Scl) contains a long region of Gly-X-X motifs and was produced by serotype M1 GAS strains. In the present study, a second member of the scl gene family was identified and designated scl2. The Scl2 protein also has a collagen-like region, which in M1 strains is composed of 38 contiguous Gly-X-X triplet motifs. The scl2 gene was present in all 50 genetically diverse GAS strains studied. The Scl2 protein is highly polymorphic, and the number of Gly-X-X motifs in the 50 strains studied ranged from 31 in one serotype M1 strain to 79 in serotype M28 and M77 isolates. The scl1 and scl2 genes were simultaneously transcribed in the exponential phase, and the Scl proteins were also produced. Sel1 and Scl2 were identified in a cell-associated form and free in culture supernatants. Production of Scl1 is regulated by Mga, a positive transcriptional regulator that controls expression of several GAS virulence factors. In contrast, production of Scl2 is controlled at the level of translation by variation in the number of short-sequence pentanucleotide repeats (CAAAA) located immediately downstream of the GTG (Val) start codon. Control of protein production by this molecular mechanism has not been identified previously in GAS. Together, the data indicate that GAS simultaneously produces two extracellular human collagen-like proteins in a regulated fashion. JF - Infection and Immunity AU - Lukomski, S AU - Nakashima, K AU - Abdi, I AU - Cipriano, V J AU - Shelvin, B J AU - Graviss, E A AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 1729 EP - 1738 VL - 69 IS - 3 SN - 0019-9567, 0019-9567 KW - Scl2 protein KW - scl2 gene KW - Microbiology Abstracts B: Bacteriology KW - Extracellular KW - Repeated sequence KW - Translation KW - Regulators KW - Proteins KW - Transcription KW - Streptococcus pyogenes KW - Collagen KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17848059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Identification+and+characterization+of+a+second+extracellular+collagen-like+protein+made+by+group+A+Streptococcus%3A+control+of+production+at+the+level+of+translation&rft.au=Lukomski%2C+S%3BNakashima%2C+K%3BAbdi%2C+I%3BCipriano%2C+V+J%3BShelvin%2C+B+J%3BGraviss%2C+E+A%3BMusser%2C+J+M&rft.aulast=Lukomski&rft.aufirst=S&rft.date=2001-03-01&rft.volume=69&rft.issue=3&rft.spage=1729&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Extracellular; Collagen; Transcription; Proteins; Translation; Regulators; Repeated sequence ER - TY - JOUR T1 - Generation of high titer antisera in rabbits by DNA immunization AN - 17829667; 4861238 AB - Mesothelin is a GPI-linked, membrane-associated differentiation antigen that is over-expressed in several forms of human cancers. Intradermal injection into rabbits of plasmid DNA encoding full length mesothelin resulted in antisera with titers as high as 1:100,000. Each immunization consisted of 320 mu g of DNA delivered into 4 sites. After the initial three injections antisera titers were moderate (between 10 to 30,000) and fell over the course of about 7 weeks. When the titers had fallen, an injection of a booster dose of DNA resulted in very high titers of antisera. These antisera contained IgGs that could bind to both recombinant mesothelin made in Eschericha coli and to mesothelin present on human cells in Western blots and in immunofluorescence assays. These observations indicate that simple intradermal DNA immunization of rabbits can result in high titers of antibodies that can be used for a variety of purposes. JF - Journal of Immunological Methods AU - Chowdhury, P S AU - Gallo, M AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Dr Msc 4255, 20892-4255 Bethesda, MD USA Y1 - 2001/03/01/ PY - 2001 DA - 2001 Mar 01 SP - 147 EP - 154 PB - Elsevier Science VL - 249 IS - 1-2 SN - 0022-1759, 0022-1759 KW - rabbits KW - Escherichia coli KW - mesothelin KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Immunology Abstracts KW - Skin KW - Immunotherapy KW - Cancer KW - Antisera KW - DNA vaccines KW - Vaccines KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W2 32365:Vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17829667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Generation+of+high+titer+antisera+in+rabbits+by+DNA+immunization&rft.au=Chowdhury%2C+P+S%3BGallo%2C+M%3BPastan%2C+I&rft.aulast=Chowdhury&rft.aufirst=P&rft.date=2001-03-01&rft.volume=249&rft.issue=1-2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA vaccines; Vaccines; Antisera; Skin; Cancer; Immunotherapy ER - TY - JOUR T1 - Pesticide Use by Persons Who Reported a High Pesticide Exposure Event in the Agricultural Health Study AN - 17818027; 4857797 AB - Almost 16% of the pesticide applicators in the Agricultural Health Study (AHS) cohort (a cohort that includes 52,629 private applicators) reported having a high pesticide exposure event (i.e., an incident or experience while using a pesticide that caused an unusually high personal exposure). Pesticides involved in these events were compared to the frequency with which specific pesticides were ever used by the AHS cohort. Generally, pesticides with greater acute toxicity were more frequently involved with the high pesticide exposure event than were other pesticides. Whereas it is clear that the use of acutely toxic pesticides may be related to more frequent visits to health care facilities, the reason that the spills and immersions of the high pesticide exposure events are associated with the acute toxicity of the pesticide is not intuitively clear. This analysis suggests that current practices directed at minimizing pesticide exposures may not be sufficient for acutely toxic or irritating chemicals. JF - Environmental Research AU - Keim, SA AU - Alavanja, M C AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, 20892, MD, USA Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 256 EP - 259 PB - Academic Press VL - 85 IS - 3 SN - 0013-9351, 0013-9351 KW - Agricultural Health Study KW - man KW - USA KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Agricultural practices KW - Pesticides KW - Toxicity KW - Agrochemicals KW - Occupational exposure KW - Pesticide applications KW - H 5000:Pesticides KW - X 24133:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17818027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=Pesticide+Use+by+Persons+Who+Reported+a+High+Pesticide+Exposure+Event+in+the+Agricultural+Health+Study&rft.au=Keim%2C+SA%3BAlavanja%2C+M+C&rft.aulast=Keim&rft.aufirst=SA&rft.date=2001-03-01&rft.volume=85&rft.issue=3&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1006%2Fenrs.2000.4224 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Agrochemicals; Pesticides; Toxicity; Pesticide applications; Agricultural practices DO - http://dx.doi.org/10.1006/enrs.2000.4224 ER - TY - JOUR T1 - Polyvalent Envelope Glycoprotein Vaccine Elicits a Broader Neutralizing Antibody Response but Is Unable To Provide Sterilizing Protection against Heterologous Simian/Human Immunodeficiency Virus Infection in Pigtailed Macaques AN - 17759033; 4822652 AB - The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus type 1 (HIV-1) isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosylation, and marked genetic variability. Most previously evaluated vaccine candidates have utilized envelope glycoprotein from a single virus isolate. Here we compare the breadth of NAb and protective immune response following vaccination of pigtailed macaques with envelope protein(s) derived from either single or multiple viral isolates. Animals were challenged with Simian/human immunodeficiency virus strain DH12 (SHIV sub(DH12)) following priming with recombinant vaccinia virus(es) expressing gp160(s) and boosting with gp120 protein(s) from (i) LAI, RF, 89.6, AD8, and Bal (Polyvalent); (ii) LAI, RF, 89.6, AD8, Bal, and DH12 (Polyvalent-DH12); (iii) 89.6 (Monovalent-89.6); and (iv) DH12 (Monovalent-DH12). Animals in the two polyvalent vaccine groups developed NAbs against more HIV-1 isolates than those in the two monovalent vaccine groups (P = 0.0054). However, the increased breadth of response was directed almost entirely against the vaccine strains. Resistance to SHIV sub(DH12) strongly correlated with the level of NAbs directed against the virus on the day of challenge (P = 0.0008). Accordingly, the animals in the Monovalent-DH12 and Polyvalent-DH12 vaccine groups were more resistant to the SHIV sub(DH12) challenge than the macaques immunized with preparations lacking a DH12 component (viz. Polyvalent and Monovalent-89.6) (P = 0.039). Despite the absence of any detectable NAb, animals in the Polyvalent vaccine group, but not those immunized with Monovalent-89.6, exhibited markedly lower levels of plasma virus than those in the control group, suggesting a superior cell-mediated immune response induced by the polyvalent vaccine. JF - Journal of Virology AU - Cho, M W AU - Kim, Y B AU - Lee, M K AU - Gupta, K C AU - Ross, W AU - Plishka, R AU - Buckler-White, A AU - Igarashi, T AU - Theodore, T AU - Byrum, R AU - Kemp, C AU - Montefiori, D C AU - Martin, MA AD - Laboratory of Molecular Microbiology, NIH, NIAID, 9000 Rockville Pike, Bldg. 4, Rm. 339, Bethesda, MD 20892-0460, mcho@nih.gov Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 2224 EP - 2234 PB - American Society for Microbiology VL - 75 IS - 5 SN - 0022-538X, 0022-538X KW - immunology KW - animal models KW - HIV KW - SIV KW - Macaques KW - Macaca nemestrina KW - glycoprotein gp120 KW - glycoprotein gp160 KW - human immunodeficiency virus KW - simian immunodeficiency virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Animal models KW - Envelopes KW - Envelope protein KW - Glycoproteins KW - Immune response (humoral) KW - Macaca KW - Antibody response KW - Immune response (cell-mediated) KW - Human immunodeficiency virus KW - Vaccines KW - Simian immunodeficiency virus KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17759033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Polyvalent+Envelope+Glycoprotein+Vaccine+Elicits+a+Broader+Neutralizing+Antibody+Response+but+Is+Unable+To+Provide+Sterilizing+Protection+against+Heterologous+Simian%2FHuman+Immunodeficiency+Virus+Infection+in+Pigtailed+Macaques&rft.au=Cho%2C+M+W%3BKim%2C+Y+B%3BLee%2C+M+K%3BGupta%2C+K+C%3BRoss%2C+W%3BPlishka%2C+R%3BBuckler-White%2C+A%3BIgarashi%2C+T%3BTheodore%2C+T%3BByrum%2C+R%3BKemp%2C+C%3BMontefiori%2C+D+C%3BMartin%2C+MA&rft.aulast=Cho&rft.aufirst=M&rft.date=2001-03-01&rft.volume=75&rft.issue=5&rft.spage=2224&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Simian immunodeficiency virus; Macaca; Envelopes; Glycoproteins; Vaccines; Antibody response; Immune response (cell-mediated); Acquired immune deficiency syndrome; Animal models; Envelope protein; Immune response (humoral) ER - TY - JOUR T1 - Secretory and Endocytic Pathways Converge in a Dynamic Endosomal System in a Primitive Protozoan AN - 1221141148; 16682685 AB - Leishmania are a group of primitive eukaryotic trypanosomatid protozoa that are apically polarized with a flagellum at their anterior end. Surrounding the base of the flagellum is the flagellar reservoir that constitutes the site for endocytosis and exocytosis in these organisms. In the present study, we define a novel multivesicular tubular compartment involved in the intracellular trafficking of macromolecules in Leishmania. This dynamic structure appears to subtend the flagellar reservoir and extends towards the posterior end of the cell. Functional domains of several surface-expressed proteins, such as the gp63 glycosyl phosphatidyl inositol anchor and the 3'nucleotidase/nuclease transmembrane domain were fused to green fluorescent protein. These chimeric proteins were found to traffic through the secretory pathway and, while reaching their intended destinations, also accumulated within the intracellular tubular compartment. Using various compounds that are efficient fluid-phase markers used to track endocytosis in higher eukaryotes, we showed that this tubular compartment constitutes an important station in the endocytic pathway of these cells. Based on our functional observations of its role in the trafficking of expressed proteins and endocytosed markers, this compartment appears to have properties similar to endosomes of higher eukaryotes. JF - Traffic AU - Ghedin, Elodie AU - Debrabant, Alain AU - Engel, Juan C AU - Dwyer, Dennis M AD - Cell Biology Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA Y1 - 2001/03// PY - 2001 DA - Mar 2001 SP - 175 EP - 188 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 2 IS - 3 SN - 1398-9219, 1398-9219 KW - ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources KW - Reservoir KW - Macromolecules KW - Leishmanolysin KW - Exocytosis KW - Green fluorescent protein KW - Nuclease KW - Transmembrane domains KW - Leishmania KW - Endocytosis KW - endosomes KW - Protozoa KW - Glycosylphosphatidylinositol KW - Flagella KW - Q1 08201:General KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1221141148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Traffic&rft.atitle=Secretory+and+Endocytic+Pathways+Converge+in+a+Dynamic+Endosomal+System+in+a+Primitive+Protozoan&rft.au=Ghedin%2C+Elodie%3BDebrabant%2C+Alain%3BEngel%2C+Juan+C%3BDwyer%2C+Dennis+M&rft.aulast=Ghedin&rft.aufirst=Elodie&rft.date=2001-03-01&rft.volume=2&rft.issue=3&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Traffic&rft.issn=13989219&rft_id=info:doi/10.1034%2Fj.1600-0854.2001.020304.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-11-01 N1 - Document feature - figure 9 N1 - Last updated - 2014-11-26 N1 - SubjectsTermNotLitGenreText - Reservoir; Flagella; Endocytosis; endosomes; Macromolecules; Leishmanolysin; Protozoa; Green fluorescent protein; Exocytosis; Nuclease; Glycosylphosphatidylinositol; Transmembrane domains; Leishmania DO - http://dx.doi.org/10.1034/j.1600-0854.2001.020304.x ER - TY - JOUR T1 - Nitric oxide induces metallothionein (MT) gene expression apparently by displacing zinc bound to MT AN - 17848635; 4883680 AB - The metal binding protein metallothionein (MT) is involved in zinc homeostasis since it typically binds large amounts of zinc. Free zinc can control MT gene expression by interacting with metal-sensitive transcription factors. However, the precise factors governing intracellular release of metal ions from MT remain unknown. Aerobic nitric oxide (NO) can nitrosate thiol groups in proteins, and MT-bound cadmium is released by NO exposure. Thus, we hypothesized that NO may also be effective at displacing zinc from MT in cultured cells and that this could be an important physiological control mechanism in zinc homeostasis and utilization. In this study, DETA/NO, an agent that spontaneously generates NO with a 20-h half life in physiological media, was used to study the release of zinc from MT and the induction of MT in TRL1215 cells (a normal rat liver cell line). Zinc or cadmium was given at levels inducing MT production, followed by DETA/NO (20-200 mu M) to produce controlled NO exposure in both cell lines. Although both metals activated MT gene expression, MT-I mRNA and MT protein were further increased when DETA/NO was given after zinc or cadmium treatment. Additionally, NO from DETA/NO clearly displaced MT-bound zinc, as evidenced by G-75 gel-filtration chromatography. The released zinc or cadmium probably then stimulates further MT gene expression. These results suggest that NO may play an important role in regulation of cellular zinc homeostasis by providing a controlled release mechanism for metal ions stored in MT, and NO-mediated release of MT-bound zinc could in turn activate gene expression, such as with the MT gene. JF - Toxicology Letters AU - Katakai, Kenji AU - Liu, Jie AU - Nakajima, Katsuyuki AU - Keefer, L K AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, NCI at NIEHS, Research, Mail Drop F0-09, 111 Alexander Drive, Research Triangle Park, NC 27709, USA, waalkes@niehs.nih.gov Y1 - 2001/02/28/ PY - 2001 DA - 2001 Feb 28 SP - 103 EP - 108 VL - 119 IS - 2 SN - 0378-4274, 0378-4274 KW - TRL1215 cells KW - Toxicology Abstracts KW - Gene expression KW - Metals KW - Metallothionein KW - Gene regulation KW - Zinc KW - Nitric oxide KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17848635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Nitric+oxide+induces+metallothionein+%28MT%29+gene+expression+apparently+by+displacing+zinc+bound+to+MT&rft.au=Katakai%2C+Kenji%3BLiu%2C+Jie%3BNakajima%2C+Katsuyuki%3BKeefer%2C+L+K%3BWaalkes%2C+M+P&rft.aulast=Katakai&rft.aufirst=Kenji&rft.date=2001-02-28&rft.volume=119&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Metals; Nitric oxide; Metallothionein; Gene expression; Gene regulation; Zinc ER - TY - JOUR T1 - MRI identification of early white matter injury in anoxic-ischemic encephalopathy. AN - 70684629; 11222791 AB - Anoxic-ischemic encephalopathy (AIE) affects the gray matter more than the white matter. Recent animal experiments suggest that the white matter is more sensitive to ischemia than previously thought. The authors describe the MRI findings in seven patients with AIE who demonstrate early preferential involvement of the white matter. A retrospective case series study was performed, including seven patients with AIE who underwent MRI of the brain within 7 days of insult. Demographic information, type of insult, clinical examination findings, EEG findings, and clinical outcome were obtained. MRI studies were reviewed with specific attention to the cortex, deep gray matter, and the white matter structures. Mean apparent diffusion coefficient (ADC) was calculated in regions of interest placed in the cerebellar hemispheres, putamen, thalamus, splenium of corpus callosum, centrum semiovale, and medial frontal cortex. The causes of AIE were cardiac arrhythmias in two patients, myocardial infarction in one, drug overdose in two, carbon monoxide poisoning in one, and respiratory failure and sepsis in one. The median time to MRI was 2.5 days. Symmetric areas of restricted diffusion were found in the periventricular white matter tracts (7/7 patients), the corpus callosum (6/7 patients), internal capsule (5/7 patients), and the subcortical association fibers (3/7 patients). ADC maps confirmed the restricted diffusion. Gray matter involvement was seen in three patients, and was more prominent on conventional imaging sequences compared with diffusion-weighted imaging. A subtle decrease in mean ADC was seen in cortex. Prominent, symmetric restricted diffusion can occur early after AIE in white matter, whereas gray matter involvement may be less prominent. Further studies involving a larger sample and serial imaging are required to confirm these preliminary findings. JF - Neurology AU - Chalela, J A AU - Wolf, R L AU - Maldjian, J A AU - Kasner, S E AD - Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA. chalelaj@ninds.nih.gov Y1 - 2001/02/27/ PY - 2001 DA - 2001 Feb 27 SP - 481 EP - 485 VL - 56 IS - 4 SN - 0028-3878, 0028-3878 KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Humans KW - Electroencephalography KW - Adult KW - Middle Aged KW - Male KW - Female KW - Hypoxia-Ischemia, Brain -- physiopathology KW - Brain -- physiopathology KW - Hypoxia-Ischemia, Brain -- pathology KW - Brain -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70684629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=MRI+identification+of+early+white+matter+injury+in+anoxic-ischemic+encephalopathy.&rft.au=Chalela%2C+J+A%3BWolf%2C+R+L%3BMaldjian%2C+J+A%3BKasner%2C+S+E&rft.aulast=Chalela&rft.aufirst=J&rft.date=2001-02-27&rft.volume=56&rft.issue=4&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 2001 Aug 28;57(4):745 [11524504] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice. AN - 70632752; 11226298 AB - Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). This enzyme deficiency leads to impaired catabolism of alpha-galactosyl-terminal lipids such as globotriaosylceramide (Gb3). Patients develop painful neuropathy and vascular occlusions that progressively lead to cardiovascular, cerebrovascular, and renal dysfunction and early death. Although enzyme replacement therapy and bone marrow transplantation have shown promise in the murine analog of Fabry disease, gene therapy holds a strong potential for treating this disease in humans. Delivery of the normal alpha-gal A gene (cDNA) into a depot organ such as liver may be sufficient to elicit corrective circulating levels of the deficient enzyme. To investigate this possibility, a recombinant adeno-associated viral vector encoding human alpha-gal A (rAAV-AGA) was constructed and injected into the hepatic portal vein of Fabry mice. Two weeks postinjection, alpha-gal A activity in the livers of rAAV-AGA-injected Fabry mice was 20-35% of that of the normal mice. The transduced animals continued to show higher alpha-gal A levels in liver and other tissues compared with the untouched Fabry controls as long as 6 months after treatment. In parallel to the elevated enzyme levels, we see significant reductions in Gb3 levels to near normal at 2 and 5 weeks posttreatment. The lower Gb3 levels continued in liver, spleen, and heart, up to 25 weeks with no significant immune response to the virus or alpha-gal A. Also, no signs of liver toxicity occurred after the rAAV-AGA administration. These findings suggest that an AAV-mediated gene transfer may be useful for the treatment of Fabry disease and possibly other metabolic disorders. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jung, S C AU - Han, I P AU - Limaye, A AU - Xu, R AU - Gelderman, M P AU - Zerfas, P AU - Tirumalai, K AU - Murray, G J AU - During, M J AU - Brady, R O AU - Qasba, P AD - Developmental and Metabolic Neurology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2001/02/27/ PY - 2001 DA - 2001 Feb 27 SP - 2676 EP - 2681 VL - 98 IS - 5 SN - 0027-8424, 0027-8424 KW - alpha-Galactosidase KW - EC 3.2.1.22 KW - Index Medicus KW - Animals KW - Liver -- physiopathology KW - Liver -- enzymology KW - Humans KW - Mice, Inbred C57BL KW - Microscopy, Electron KW - Mice KW - Cell Line KW - Fabry Disease -- therapy KW - Gene Transfer Techniques KW - Fabry Disease -- immunology KW - Genetic Vectors KW - Dependovirus -- genetics KW - alpha-Galactosidase -- genetics KW - Fabry Disease -- enzymology KW - alpha-Galactosidase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Adeno-associated+viral+vector-mediated+gene+transfer+results+in+long-term+enzymatic+and+functional+correction+in+multiple+organs+of+Fabry+mice.&rft.au=Jung%2C+S+C%3BHan%2C+I+P%3BLimaye%2C+A%3BXu%2C+R%3BGelderman%2C+M+P%3BZerfas%2C+P%3BTirumalai%2C+K%3BMurray%2C+G+J%3BDuring%2C+M+J%3BBrady%2C+R+O%3BQasba%2C+P&rft.aulast=Jung&rft.aufirst=S&rft.date=2001-02-27&rft.volume=98&rft.issue=5&rft.spage=2676&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):365-70 [10618424] Science. 2000 Feb 25;287(5457):1453-60 [10688787] Res Exp Med (Berl). 2000 Apr;199(5):263-74 [10815755] Infect Immun. 2000 Jun;68(6):3564-8 [10816512] J Clin Invest. 2000 Jun;105(11):1563-71 [10841515] Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7515-20 [10840053] Mol Ther. 2000 Apr;1(4):323-9 [10933950] Mol Ther. 2000 Feb;1(2):154-8 [10933925] J Virol. 2000 Oct;74(20):9451-63 [11000214] Nature. 2000 Nov 23;408(6811):483-8 [11100731] Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9 [11095710] N Engl J Med. 1967 May 25;276(21):1163-7 [6023233] J Lipid Res. 1969 Mar;10(2):188-92 [5782355] N Engl J Med. 1973 Jul 5;289(1):9-14 [4196713] J Lipid Res. 1977 May;18(3):371-8 [405444] J Gen Virol. 1977 Jul;36(1):59-74 [886304] J Biol Chem. 1978 Jan 10;253(1):184-90 [201618] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Acta Histochem. 1985;77(1):33-6 [3933254] Proc Natl Acad Sci U S A. 1986 Jul;83(13):4859-63 [3014515] Annu Rev Biochem. 1986;55:167-93 [2943218] J Virol. 1989 Sep;63(9):3822-8 [2547998] J Lipid Res. 1990 Feb;31(2):335-40 [2157788] Annu Rev Biochem. 1991;60:257-80 [1883197] Nature. 1992 Dec 24-31;360(6406):749-53 [1465145] Clin Genet. 1993 Dec;44(6):302-6 [8131301] Hum Gene Ther. 1995 Jul;6(7):905-15 [7578409] Gene. 1995 Dec 12;166(2):277-80 [8543175] J Virol. 1996 Nov;70(11):8098-108 [8892935] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14082-7 [8943064] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1287-92 [9037045] Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2540-4 [9122231] Blood. 1998 Jun 15;91(12):4600-7 [9616156] Proc Natl Acad Sci U S A. 1999 May 25;96(11):6423-7 [10339603] Hum Gene Ther. 1999 Jul 1;10(10):1667-82 [10428212] Hum Gene Ther. 1999 Aug 10;10(12):1931-9 [10466627] J Lipid Res. 1965 Jul;6:428-31 [14336214] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3903-7 [2836863] J Biol Chem. 1989 Jul 25;264(21):12115-8 [2545698] N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Sex differences in mate size preference in the convict cichlid, Cichlasoma nigrofasciatum AN - 39363515; 3566195 AU - Beeching, S AU - Hopp, AB AU - Ruffner, G L Y1 - 2001/02/26/ PY - 2001 DA - 2001 Feb 26 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39363515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Sex+differences+in+mate+size+preference+in+the+convict+cichlid%2C+Cichlasoma+nigrofasciatum&rft.au=Beeching%2C+S%3BHopp%2C+AB%3BRuffner%2C+G+L&rft.aulast=Beeching&rft.aufirst=S&rft.date=2001-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Animal Behavior Society, Indiana University, 2611 East 10th Street #170, Bloomington IN 47408-2603, USA; phone: 812-856-5541; fax: 812-856-5542; URL: http://www.animalbehavior.org/ABS/. Paper No. 25 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Who does what to whom?: Affiliative behavior in common marmoset nuclear families AN - 39277644; 3566274 AU - Lawler, T AU - Jenkins, K T AU - Newman, J D AU - Roberts, R L Y1 - 2001/02/26/ PY - 2001 DA - 2001 Feb 26 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39277644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Who+does+what+to+whom%3F%3A+Affiliative+behavior+in+common+marmoset+nuclear+families&rft.au=Lawler%2C+T%3BJenkins%2C+K+T%3BNewman%2C+J+D%3BRoberts%2C+R+L&rft.aulast=Lawler&rft.aufirst=T&rft.date=2001-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Animal Behavior Society, Indiana University, 2611 East 10th Street #170, Bloomington IN 47408-2603, USA; phone: 812-856-5541; fax: 812-856-5542; URL: http://www.animalbehavior.org/ABS/. Paper No. 171 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Evolution of the two-step model for UV-mutagenesis. AN - 70818101; 11341996 AB - It is quite remarkable how our understanding of translesion DNA synthesis (TLS) has changed so dramatically in the past 2 years. Until very recently, little was known about the molecular mechanisms of TLS in higher eukaryotes and what we did know, was largely based upon Escherichia coli and Saccharomyces cerevisiae model systems. The paradigm, proposed by Bryn Bridges and I [Mutat. Res. 150 (1985) 133] in 1985, was that error-prone TLS occurred in two steps; namely a misinsertion event opposite a lesion, followed by extension of the mispair so as to facilitate complete bypass of the lesion. The initial concept was that at least for E. coli, the misinsertion event was performed by the cell's main replicase, DNA polymerase III holoenzyme, and that elongation was achieved through the actions of specialized polymerase accessory proteins, such as UmuD and UmuC. Some 15 years later, we now know that this view is likely to be incorrect in that both misinsertion and bypass are performed by the Umu proteins (now called pol V). As pol V is normally a distributive enzyme, pol III may only be required to "fix" the misincorporation as a mutation by completing chromosome duplication. However, while the role of the E. coli proteins involved in TLS have changed, the initial concept of misincorporation followed by extension/bypass remains valid. Indeed, recent evidence suggests that it can equally be applied to TLS in eukaryotic cells where there are many more DNA polymerases to choose from. The aim of this review is, therefore, to provide a historical perspective to the "two-step" model for UV-mutagenesis, how it has recently evolved, and in particular, to highlight the seminal contributions made to it by Bryn Bridges. JF - Mutation research AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, MD 20892-2725, USA. woodgate@helix.nih.gov Y1 - 2001/02/25/ PY - 2001 DA - 2001 Feb 25 SP - 83 EP - 92 VL - 485 IS - 1 SN - 0027-5107, 0027-5107 KW - Escherichia coli Proteins KW - 0 KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase V, E coli KW - EC 2.7.7.7 KW - DNA-Directed DNA Polymerase KW - Index Medicus KW - Bridges KW - Escherichia coli -- metabolism KW - Genes, Bacterial KW - History, 20th Century KW - Escherichia coli -- genetics KW - SOS Response (Genetics) -- physiology KW - SOS Response (Genetics) -- genetics KW - Ultraviolet Rays -- adverse effects KW - DNA Polymerase III -- genetics KW - Eukaryotic Cells KW - DNA Polymerase III -- metabolism KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism KW - Escherichia coli -- radiation effects KW - Models, Genetic KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70818101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Evolution+of+the+two-step+model+for+UV-mutagenesis.&rft.au=Woodgate%2C+R&rft.aulast=Woodgate&rft.aufirst=R&rft.date=2001-02-25&rft.volume=485&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - People - Bridges N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Bridges ER - TY - JOUR T1 - Signaling pathways underlying muscarinic receptor-induced [Ca2+]i oscillations in HEK293 cells. AN - 70612652; 11096083 AB - We have investigated the signaling pathways underlying muscarinic receptor-induced calcium oscillations in human embryonic kidney (HEK293) cells. Activation of muscarinic receptors with a maximal concentration of carbachol (100 microm) induced a biphasic rise in cytoplasmic calcium ([Ca2+]i) comprised of release of Ca2+ from intracellular stores and influx of Ca2+ from the extracellular space. A lower concentration of carbachol (5 microm) induced repetitive [Ca2+]i spikes or oscillations, the continuation of which was dependent on extracellular Ca2+. The entry of Ca2+ with 100 microm carbachol and with the sarcoplasmic-endoplasmic reticulum calcium ATPase inhibitor, thapsigargin, was completely blocked by 1 microm Gd3+, as well as 30-100 microm concentrations of the membrane-permeant inositol 1,4,5-trisphosphate receptor inhibitor, 2-aminoethyoxydiphenyl borane (2-APB). Sensitivity to these inhibitors is indicative of capacitative calcium entry. Arachidonic acid, a candidate signal for Ca2+ entry associated with [Ca2+]i oscillations in HEK293 cells, induced entry that was inhibited only by much higher concentrations of Gd3+ and was unaffected by 100 microm 2-APB. Like arachidonic acid-induced entry, the entry associated with [Ca2)]i oscillations was insensitive to inhibition by Gd3+ but was completely blocked by 100 microm 2-APB. These findings indicate that the signaling pathway responsible for the Ca2+) entry driving [Ca2+]i oscillations in HEK293 cells is more complex than originally thought, and may involve neither capacitative calcium entry nor a role for PLA2 and arachidonic acid. JF - The Journal of biological chemistry AU - Luo, D AU - Broad, L M AU - Bird, G S AU - Putney, J W AD - Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/02/23/ PY - 2001 DA - 2001 Feb 23 SP - 5613 EP - 5621 VL - 276 IS - 8 SN - 0021-9258, 0021-9258 KW - Boron Compounds KW - 0 KW - Receptors, Muscarinic KW - Arachidonic Acid KW - 27YG812J1I KW - Thapsigargin KW - 67526-95-8 KW - Carbachol KW - 8Y164V895Y KW - Gadolinium KW - AU0V1LM3JT KW - 2-aminoethoxydiphenyl borate KW - E4ES684O93 KW - Index Medicus KW - Thapsigargin -- pharmacology KW - Gadolinium -- pharmacology KW - Drug Interactions KW - Boron Compounds -- pharmacology KW - Humans KW - Arachidonic Acid -- pharmacology KW - Biological Transport KW - Carbachol -- pharmacology KW - Calcium Signaling KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70612652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Signaling+pathways+underlying+muscarinic+receptor-induced+%5BCa2%2B%5Di+oscillations+in+HEK293+cells.&rft.au=Luo%2C+D%3BBroad%2C+L+M%3BBird%2C+G+S%3BPutney%2C+J+W&rft.aulast=Luo&rft.aufirst=D&rft.date=2001-02-23&rft.volume=276&rft.issue=8&rft.spage=5613&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solvent-free synthesis of benzo[a]pyrene 7,8-diol 9,10-epoxide adducts at the N(2)-position of deoxyguanosine. AN - 70632144; 11178817 AB - [reaction: see text] The first solid-state (or solvent-free) synthesis of protected deoxyguanosine (dG) adducts of benzo[a]pyrene diol epoxides at room temperature is reported. Whereas dG adducts derived from cis- and trans-opening of (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-1 1) are formed as a 1:1 mixture, the direct opening of the diastereomeric (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-2, 2) produced a 15:85 ratio favoring the trans-opened dG adduct 7. JF - Organic letters AU - Ramesha, A R AU - Kroth, H AU - Jerina, D M AD - Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 SP - 531 EP - 533 VL - 3 IS - 4 SN - 1523-7060, 1523-7060 KW - DNA Adducts KW - 0 KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - 7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine KW - 62698-04-8 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Molecular Structure KW - Stereoisomerism KW - Molecular Conformation KW - Structure-Activity Relationship KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - DNA Adducts -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemical synthesis KW - Deoxyguanosine -- chemical synthesis KW - Deoxyguanosine -- chemistry KW - DNA Adducts -- chemical synthesis KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Organic+letters&rft.atitle=Solvent-free+synthesis+of+benzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide+adducts+at+the+N%282%29-position+of+deoxyguanosine.&rft.au=Ramesha%2C+A+R%3BKroth%2C+H%3BJerina%2C+D+M&rft.aulast=Ramesha&rft.aufirst=A&rft.date=2001-02-22&rft.volume=3&rft.issue=4&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=Organic+letters&rft.issn=15237060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - New insights into the role of formyl peptide receptors: Implications for AIDS and Alzheimer's disease AN - 39303261; 3558967 AU - Wang, J M AU - Le, Y AU - Oppenheim, J J Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39303261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=New+insights+into+the+role+of+formyl+peptide+receptors%3A+Implications+for+AIDS+and+Alzheimer%27s+disease&rft.au=Wang%2C+J+M%3BLe%2C+Y%3BOppenheim%2C+J+J&rft.aulast=Wang&rft.aufirst=J&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Hut 78 cell: DNA methyltransferase and HIV-1 infection AN - 39302370; 3559015 AU - Fang, J Y AU - Mikovits, JA AU - Bagui, R AU - Ruscetti, F W Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39302370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Hut+78+cell%3A+DNA+methyltransferase+and+HIV-1+infection&rft.au=Fang%2C+J+Y%3BMikovits%2C+JA%3BBagui%2C+R%3BRuscetti%2C+F+W&rft.aulast=Fang&rft.aufirst=J&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Induction of discoidin domain receptor 1 in human leukocytes AN - 39302060; 3558945 AU - Kamohara, H AU - Yamashiro, S AU - Yoshimura, T Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39302060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Induction+of+discoidin+domain+receptor+1+in+human+leukocytes&rft.au=Kamohara%2C+H%3BYamashiro%2C+S%3BYoshimura%2C+T&rft.aulast=Kamohara&rft.aufirst=H&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Enhanced toll-like receptor (TLR4) expression in TGF-b1 null mice AN - 39300650; 3558974 AU - McCartney-Francis, N AU - Mizel, D AU - Wahl, S M Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39300650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Enhanced+toll-like+receptor+%28TLR4%29+expression+in+TGF-b1+null+mice&rft.au=McCartney-Francis%2C+N%3BMizel%2C+D%3BWahl%2C+S+M&rft.aulast=McCartney-Francis&rft.aufirst=N&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Efficient transfer of human MDR1 cDNA or GFP into hematopoetic cells expressing MHC class I using an SV40 in-vitro packaging delivery system AN - 39280521; 3572518 AU - Kimchi-Sarfaty, C Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39280521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Efficient+transfer+of+human+MDR1+cDNA+or+GFP+into+hematopoetic+cells+expressing+MHC+class+I+using+an+SV40+in-vitro+packaging+delivery+system&rft.au=Kimchi-Sarfaty%2C+C&rft.aulast=Kimchi-Sarfaty&rft.aufirst=C&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Professional Conference Management Inc., 7916 Convoy Court, San Diego, California 92111-1212, USA; phone: 858-565-9921; fax: 858-565-9954; email: pcminc@pcmisandiego.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Structure-based mechanisms of nucleotide insertion fidelity AN - 39280416; 3560631 AU - Wilson, S Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39280416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Structure-based+mechanisms+of+nucleotide+insertion+fidelity&rft.au=Wilson%2C+S&rft.aulast=Wilson&rft.aufirst=S&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Gordon Research Conferences, University of Rhode Island, P.O. Box 984, West Kingston, RI 02892-0984, USA; phone: 401-783-4011; fax: 401-783-7644; URL: www.grc.uri.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Enhanced susceptibility of tonsil lymphoid cells to HIV infection in vivo and in vitro AN - 39275536; 3558892 AU - Moutsopoulos, N M AU - Wild, R AU - Horn, J AU - Orenstein, J M AU - Wahl, S M Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39275536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Enhanced+susceptibility+of+tonsil+lymphoid+cells+to+HIV+infection+in+vivo+and+in+vitro&rft.au=Moutsopoulos%2C+N+M%3BWild%2C+R%3BHorn%2C+J%3BOrenstein%2C+J+M%3BWahl%2C+S+M&rft.aulast=Moutsopoulos&rft.aufirst=N&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Pol-iota, a remarkably error-prone DNA polymerase AN - 39233593; 3560647 AU - Woodgate, R Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39233593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Pol-iota%2C+a+remarkably+error-prone+DNA+polymerase&rft.au=Woodgate%2C+R&rft.aulast=Woodgate&rft.aufirst=R&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Gordon Research Conferences, University of Rhode Island, P.O. Box 984, West Kingston, RI 02892-0984, USA; phone: 401-783-4011; fax: 401-783-7644; URL: www.grc.uri.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Human PMN can be driven by selected cytokines to acquire some of the phenotypic and functional features of dendritic cells AN - 39217890; 3558972 AU - Yoshimura, T AU - Yamashiro, S AU - Wang, J-M AU - Yang, D AU - Gong, W-H AU - Kamohara, H Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39217890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Human+PMN+can+be+driven+by+selected+cytokines+to+acquire+some+of+the+phenotypic+and+functional+features+of+dendritic+cells&rft.au=Yoshimura%2C+T%3BYamashiro%2C+S%3BWang%2C+J-M%3BYang%2C+D%3BGong%2C+W-H%3BKamohara%2C+H&rft.aulast=Yoshimura&rft.aufirst=T&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Mobilization of various types of leukocytes by human granulocyte-derived antimicrobial proteins: Identification of novel activities and/or receptors for defensins, cathelicidin, and eosinophil-derived neurotoxin AN - 39217836; 3558961 AU - Yang, D AU - Chertov, O AU - Rosenberg, H F AU - Chen, Q AU - Anderson, M AU - Schroeder, J M AU - Oppenheim, J J Y1 - 2001/02/22/ PY - 2001 DA - 2001 Feb 22 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39217836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Mobilization+of+various+types+of+leukocytes+by+human+granulocyte-derived+antimicrobial+proteins%3A+Identification+of+novel+activities+and%2For+receptors+for+defensins%2C+cathelicidin%2C+and+eosinophil-derived+neurotoxin&rft.au=Yang%2C+D%3BChertov%2C+O%3BRosenberg%2C+H+F%3BChen%2C+Q%3BAnderson%2C+M%3BSchroeder%2C+J+M%3BOppenheim%2C+J+J&rft.aulast=Yang&rft.aufirst=D&rft.date=2001-02-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Ohio State University, Engineering Experiment Station, 2070 Neil Ave., Room 025, Columbus, OH 43210, USA N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Recent trends in lung cancer mortality in the United States. AN - 70639156; 11181774 AB - Previous age-period-cohort analyses of lung cancer incidence and mortality rates in the United States have demonstrated a decrease in risk by birth cohort through 1950, consistent with declining trends in smoking prevalence. This study was conducted to examine recent lung cancer trends, including trends among the cohorts born after 1950. Lung cancer mortality rates from 1970 through 1997 for whites aged 24--83 years and for blacks aged 30--83 years were investigated. Using age--period--cohort analyses with 2-year age and 2-year calendar-period intervals, we examined changes in the slope of the trends in birth-cohort and calendar-period effects. All statistical tests are two-sided. There was an unexpected, statistically significant moderation in the rate of decrease of the birth-cohort trend in lung cancer mortality for whites born after 1950, with a corresponding smaller and statistically nonsignificant moderation for blacks. These data are consistent with smoking initiation rates: Rates of both cigarette and marijuana smoking initiation increased for children aged 12--17 years from 1965 through 1977. There was a statistically significant decrease in the slope of the calendar-period trend for lung cancer mortality in 1990 for both whites and blacks that was observed primarily in people 55 years of age and older. The birth-cohort pattern of lung cancer mortality after 1950 appears to reflect the early impact of teenage cigarette smoking on lung cancer risk in people under the age of 45 years, although a contribution from marijuana smoking cannot be ruled out. This result provides additional support for increasing smoking cessation and prevention programs for teenagers. The calendar-period decrease in lung cancer mortality after 1990 may reflect the long-term benefits of reductions in tobacco carcinogens in cigarettes and increases in smoking cessation beginning around 1960. JF - Journal of the National Cancer Institute AU - Jemal, A AU - Chu, K C AU - Tarone, R E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda 20982, MD, USA. Jemala@exchange.nih.gov Y1 - 2001/02/21/ PY - 2001 DA - 2001 Feb 21 SP - 277 EP - 283 VL - 93 IS - 4 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Humans KW - African Americans -- statistics & numerical data KW - Marijuana Smoking -- epidemiology KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - Mortality -- trends KW - Risk KW - Aged, 80 and over KW - Adult KW - Cohort Studies KW - Middle Aged KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Prevalence KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Smoking -- adverse effects KW - Lung Neoplasms -- mortality KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70639156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Recent+trends+in+lung+cancer+mortality+in+the+United+States.&rft.au=Jemal%2C+A%3BChu%2C+K+C%3BTarone%2C+R+E&rft.aulast=Jemal&rft.aufirst=A&rft.date=2001-02-21&rft.volume=93&rft.issue=4&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and Immunogenicity Trial in Adult Volunteers of a Human Papillomavirus 16 L1 Virus-Like Particle Vaccine AN - 17837497; 4868853 AB - Studies in animal models have shown that systemic immunization with a papillomavirus virus-like particle (VLP) vaccine composed of L1, a major structural viral protein, can confer protection against subsequent experimental challenge with the homologous virus. Here we report results of a double-blind, placebo-controlled, dose-escalation trial to evaluate the safety and immunogenicity of a human papillomavirus (HPV) type 16 (HPV16) L1 VLP vaccine in healthy adults. Volunteers were given intramuscular injections with placebo or with 10- or 50- mu g doses of HPV16 L1 VLP vaccine given without adjuvant or with alum or MF59 as adjuvants at 0, 1, and 4 months. All vaccine recipients were monitored for clinical signs and symptoms for 7 days after each inoculation. Immune responses were measured by an HPV16 L1 VLP-based enzyme-linked immunosorbent assay (ELISA) and by an HPVI6 pseudovirion neutralization assay. The antibody titers were given as the reciprocals of the highest dilution showing positive reactivity in each assay. All statistical tests were two-sided. The prevaccination geometric mean ELISA titer for six seropositive individuals was 202 (range, 40-640). All vaccine formulations were well tolerated, and all subjects receiving vaccine seroconverted. Serum antibody responses at 1 month after the third injection were dose dependent in recipients of vaccine without adjuvant or with MF59 but were similar at both doses when alum was the adjuvant. With the higher dose, the geometric means of serum ELISA antibody titers (95% confidence intervals) to purified VLP 1 month after the third injection were as follows: 10240 (1499 to 69938) without adjuvant, 10240 (1114 to 94145) with MF59, and 2190 (838 to 5723) with alum. Responses of subjects within each group were similar. Neutralizing and ELISA antibody titers were highly correlated (Spearman correlation = .85), confirming that ELISA titers are valid proxies for neutralizing antibodies. The HPV16 L1 VLP vaccine is well tolerated and is highly immunogenic even without adjuvant, with the majority of the recipients achieving serum antibody titers that were approximately 40-fold higher than what is observed in natural infection. JF - Journal of the National Cancer Institute AU - Harro, C D AU - Pang, Y-YS AU - Roden, RBS AU - Hildesheim, A AU - Wang, Zhaohui AU - Reynolds, MJ AU - Mast, T C AU - Robinson, R AU - Murphy, B R AU - Karron, R A AU - Dillner, J AU - Schiller, J T AU - Lowy AD - National Institutes of Health, Bldg. 36, Rm. ID-32, Bethesda, MD 20892, USA, drl@helix.nih.gov Y1 - 2001/02/21/ PY - 2001 DA - 2001 Feb 21 SP - 284 EP - 292 VL - 93 IS - 4 SN - 0027-8874, 0027-8874 KW - intramuscular injection KW - Human papillomavirus 16 KW - clinical trials KW - immune response KW - immunogenicity KW - vaccines KW - Biotechnology and Bioengineering Abstracts; Health & Safety Science Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Risk assessment KW - Virus-like particles KW - Safety KW - Adults KW - Adjuvants KW - Clinical trials KW - Immunogenicity KW - Vaccines KW - Immune response KW - W3 33365:Vaccines (other) KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17837497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Safety+and+Immunogenicity+Trial+in+Adult+Volunteers+of+a+Human+Papillomavirus+16+L1+Virus-Like+Particle+Vaccine&rft.au=Harro%2C+C+D%3BPang%2C+Y-YS%3BRoden%2C+RBS%3BHildesheim%2C+A%3BWang%2C+Zhaohui%3BReynolds%2C+MJ%3BMast%2C+T+C%3BRobinson%2C+R%3BMurphy%2C+B+R%3BKarron%2C+R+A%3BDillner%2C+J%3BSchiller%2C+J+T%3BLowy&rft.aulast=Harro&rft.aufirst=C&rft.date=2001-02-21&rft.volume=93&rft.issue=4&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human papillomavirus 16; Risk assessment; Immunogenicity; Clinical trials; Adjuvants; Immune response; Adults; Safety; Virus-like particles; Vaccines ER - TY - JOUR T1 - Mutations of an epitope hot-spot residue alter rate limiting steps of antigen-antibody protein-protein associations. AN - 70811817; 11329268 AB - The antibodies, HyHEL-10 and HyHEL-26 (H10 and H26, respectively), share over 90% sequence homology and recognize with high affinity the same epitope on hen egg white lysozyme (HEL) but differ in degree of cross-reactivity with mutant lysozymes. The binding kinetics, as measured by BIAcore surface plasmon resonance, of monovalent Fab from both Abs (Fab10 and Fab26) to HEL and mutant lysozymes are best described by a two-step association model consistent with an encounter followed by docking that may include conformational changes. In their complexes with HEL, both Abs make the transition to the docked phase rapidly. For H10, the encounter step is rate limiting, whereas docking is also partially rate limiting for H26. The forward rate constants of H10 are higher than those of H26. The docking equilibrium as well as the overall equilibrium constant are also higher for H10 than for H26. Most of the free energy change of association (Delta G degrees) occurs during the encounter phase (Delta G1) of both Abs. H10 derives a greater amount and proportion of free energy change from the docking phase (Delta G2) than does H26. In the H10--HEL(R21Q) complex, a significant slowing of docking results in lowered affinity, a loss of most of Delta G2, and apparently faster dissociation. Slower encounter and docking cause lowered affinity and a loss of free energy change primarily in the encounter step (Delta G1) of H26 with mutant HEL(R21Q). Overall, in the process of complex formation with lysozyme, the mutations HEL(R21X) affect primarily the docking phase of H10 association and both phases of H26. Our results are consistent with the interpretation that the free energy barriers to conformational rearrangement are highest in H26, especially with mutant antigen. JF - Biochemistry AU - Li, Y AU - Lipschultz, C A AU - Mohan, S AU - Smith-Gill, S J AD - Basic Research Laboratory, Program in Structural Biology, National Cancer Institute, Frederick Cancer Research and Development Center, P.O. Box B, Building 469, Room 206, Frederick, Maryland 21702-1201, USA. Y1 - 2001/02/20/ PY - 2001 DA - 2001 Feb 20 SP - 2011 EP - 2022 VL - 40 IS - 7 SN - 0006-2960, 0006-2960 KW - Antibodies, Monoclonal KW - 0 KW - Enzymes, Immobilized KW - Epitopes KW - Ligands KW - Muramidase KW - EC 3.2.1.17 KW - Index Medicus KW - Animals KW - Thermodynamics KW - Antibodies, Monoclonal -- metabolism KW - Enzymes, Immobilized -- metabolism KW - Enzymes, Immobilized -- genetics KW - Models, Statistical KW - Enzymes, Immobilized -- immunology KW - Ovum KW - Antibody Affinity -- genetics KW - Chickens KW - Models, Immunological KW - Amino Acid Substitution -- genetics KW - Binding Sites, Antibody -- genetics KW - Dose-Response Relationship, Immunologic KW - Kinetics KW - Models, Chemical KW - Time Factors KW - Mutagenesis, Site-Directed KW - Epitopes -- genetics KW - Muramidase -- genetics KW - Muramidase -- immunology KW - Epitopes -- immunology KW - Muramidase -- metabolism KW - Antigen-Antibody Reactions -- genetics KW - Epitopes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70811817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Mutations+of+an+epitope+hot-spot+residue+alter+rate+limiting+steps+of+antigen-antibody+protein-protein+associations.&rft.au=Li%2C+Y%3BLipschultz%2C+C+A%3BMohan%2C+S%3BSmith-Gill%2C+S+J&rft.aulast=Li&rft.aufirst=Y&rft.date=2001-02-20&rft.volume=40&rft.issue=7&rft.spage=2011&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of human CYP2C19 residues that confer S-mephenytoin 4'-hydroxylation activity to CYP2C9. AN - 70806551; 11329260 AB - CYP2C19 is selective for the 4'-hydroxylation of S-mephenytoin while the highly similar CYP2C9 has little activity toward this substrate. To identify critical amino acids determining the specificity of human CYP2C19 for S-mephenytoin 4'-hydroxylation, we constructed chimeras by replacing portions of CYP2C9 containing various proposed substrate recognition sites (SRSs) with those of CYP2C19 and mutating individual residues by site-directed mutagenesis. Only a chimera containing regions encompassing SRSs 1--4 was active (30% of wild-type CYP2C19), indicating that multiple regions are necessary to confer specificity for S-mephenytoin. Mutagenesis studies identified six residues in three topological components of the proteins required to convert CYP2C9 to an S-mephenytoin 4'-hydroxylase (6% of the activity of wild-type CYP2C19). Of these, only the I99H difference located in SRS 1 between helices B and C reflects a change in a side chain that is predicted to be in the substrate-binding cavity formed above the heme prosthetic group. Two additional substitutions, S220P and P221T residing between helices F and G but not in close proximity to the substrate binding site together with five differences in the N-terminal portion of helix I conferred S-mephenytoin 4'-hydroxylation activity with a K(M) similar to that of CYP2C19 but a 3-fold lower K(cat). Three residues in helix I, S286N, V292A, and F295L, were essential for S-mephenytoin 4'-hydroxylation activity. On the basis of the structure of the closely related enzyme CYP2C5, these residues are unlikely to directly contact the substrate during catalysis but are positioned to influence the packing of substrate binding site residues and likely substrate access channels in the enzyme. JF - Biochemistry AU - Tsao, C C AU - Wester, M R AU - Ghanayem, B AU - Coulter, S J AU - Chanas, B AU - Johnson, E F AU - Goldstein, J A AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/02/20/ PY - 2001 DA - 2001 Feb 20 SP - 1937 EP - 1944 VL - 40 IS - 7 SN - 0006-2960, 0006-2960 KW - Peptide Fragments KW - 0 KW - Recombinant Fusion Proteins KW - Isoleucine KW - 04Y7590D77 KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - Histidine KW - 4QD397987E KW - Asparagine KW - 7006-34-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Proline KW - 9DLQ4CIU6V KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Steroid 16-alpha-Hydroxylase KW - Mephenytoin KW - R420KW629U KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Threonine -- genetics KW - Peptide Fragments -- genetics KW - Humans KW - Substrate Specificity -- genetics KW - Serine -- genetics KW - Hydroxylation KW - Recombinant Fusion Proteins -- metabolism KW - Isoleucine -- genetics KW - Mutagenesis, Site-Directed KW - Proline -- genetics KW - Histidine -- genetics KW - Kinetics KW - Asparagine -- genetics KW - Recombinant Fusion Proteins -- chemical synthesis KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Amino Acid Substitution -- genetics KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid Hydroxylases -- genetics KW - Mixed Function Oxygenases -- genetics KW - Mephenytoin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70806551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Identification+of+human+CYP2C19+residues+that+confer+S-mephenytoin+4%27-hydroxylation+activity+to+CYP2C9.&rft.au=Tsao%2C+C+C%3BWester%2C+M+R%3BGhanayem%2C+B%3BCoulter%2C+S+J%3BChanas%2C+B%3BJohnson%2C+E+F%3BGoldstein%2C+J+A&rft.aulast=Tsao&rft.aufirst=C&rft.date=2001-02-20&rft.volume=40&rft.issue=7&rft.spage=1937&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the human motor cortex in rapid motor learning AN - 18147060; 4846762 AB - Recent studies suggest that the human primary motor cortex (M1) is involved in motor learning, but the nature of that involvement is not clear. Here, learning-related changes in M1 excitability were studied with transcranial magnetic stimulation (TMS) while naive subjects practiced either a ballistic or a ramp pinch task to the 0.5-Hz beat of a metronome. Subjects rapidly learned to optimize ballistic contractions as indicated by a significant increase in peak pinch acceleration and peak force after the 60-min practice epoch. The increase in force and acceleration was associated with an increase in motor evoked potential (MEP) amplitude in a muscle involved in the training (flexor policis brevis) but not in a muscle unrelated to the task (abductor digiti minimi). MEPs returned to their baseline amplitude after subjects had acquired the new skill, whereas no practice-induced changes in MEP amplitude were observed after subjects had overlearned the task, or after practicing slow ramp pinches. Since the changes in MEP amplitude were observed only after TMS of M1 but not after direct stimulation of the corticospinal tract, these findings indicate task- and effector-specific involvement of human M1 in rapid motor learning. JF - Experimental Brain Research AU - Muellbacher, W AU - Ziemann, U AU - Boroojerdi, B AU - Cohen, L AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5N226, 10 Center Drive MSC-1428, Bethesda, MD 20892-1428, USA, hallettm@ninds.nih.gov Y1 - 2001/02/19/ PY - 2001 DA - 2001 Feb 19 SP - 431 EP - 438 PB - Springer-Verlag VL - 136 IS - 4 SN - 0014-4819, 0014-4819 KW - man KW - CSA Neurosciences Abstracts; Physical Education Index KW - Cortex (motor) KW - Learning KW - Motor learning KW - Behavior KW - Motor task performance KW - Motor performance KW - Brain KW - Learning behavior KW - Muscles (contractions) KW - N3 11135:Physiological and biophysical correlates KW - PE 080:Motor Learning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18147060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+Brain+Research&rft.atitle=Role+of+the+human+motor+cortex+in+rapid+motor+learning&rft.au=Muellbacher%2C+W%3BZiemann%2C+U%3BBoroojerdi%2C+B%3BCohen%2C+L%3BHallett%2C+M&rft.aulast=Muellbacher&rft.aufirst=W&rft.date=2001-02-19&rft.volume=136&rft.issue=4&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Experimental+Brain+Research&rft.issn=00144819&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Brain; Motor learning; Motor performance; Muscles (contractions); Learning; Behavior; Cortex (motor); Motor task performance; Learning behavior ER - TY - JOUR T1 - Cellular sites of H2O2-induced damage and their protection by nitroxides. AN - 70819240; 11342255 AB - While the exact mechanism of H2O2-induced cytotoxicity is unknown, there is considerable evidence implicating DNA as a primary target. A recent study showed that a cell-impermeable nitroxide protected mammalian cells from H2O2-induced cell killing and suggested that the protection was mediated through cell membrane-bound or extracellular factors. To further define the protective properties of nitroxides, Chinese hamster V79 cells were exposed to H2O2 with or without cell-permeable and impermeable nitroxides and selected metal chelators. EPR spectroscopy and paramagnetic line broadening agents were used to distinguish between intra- and extracellular nitroxide distribution. To study the effectiveness of nitroxide protection, in the absence of a cell membrane, H2O2-mediated damage to supercoiled plasmid DNA was evaluated. Both deferrioxamine and Tempol cross the cell membrane, and inhibited H2O2-mediated cell killing, whereas the cell-impermeable DTPA and nitroxide, CAT-1, failed to protect. Similar protective effects of the chelators and nitroxides were observed when L-histidine, which enhances intracellular injury, was added to H2O2. In contrast, when damage to plasmid DNA was induced (in the absence of a cell membrane), both nitroxides were protective. Collectively, these results do not support a role for membrane-bound or extracellular factors in mediating H2O2 cytotoxicity in mammalian cells. JF - Biochimica et biophysica acta AU - Samuni, A M AU - DeGraff, W AU - Krishna, M C AU - Mitchell, J B AD - Radiation Biology Branch, Division of Clinical Sciences, Bldg. 10 Rm B3B69, National Cancer Institute, NIH, Bethesda, MD 20892-1002, USA. Y1 - 2001/02/16/ PY - 2001 DA - 2001 Feb 16 SP - 70 EP - 76 VL - 1525 IS - 1-2 SN - 0006-3002, 0006-3002 KW - Antioxidants KW - 0 KW - Chelating Agents KW - Cyclic N-Oxides KW - Nitrogen Oxides KW - Spin Labels KW - Histidine KW - 4QD397987E KW - Hydrogen Peroxide KW - BBX060AN9V KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Animals KW - DNA Damage KW - Chelating Agents -- pharmacology KW - Antioxidants -- pharmacology KW - Cell Survival -- drug effects KW - Cyclic N-Oxides -- pharmacology KW - Antioxidants -- pharmacokinetics KW - Cell Membrane Permeability KW - Cell Line KW - Cricetinae KW - Cyclic N-Oxides -- pharmacokinetics KW - Histidine -- pharmacology KW - Hydrogen Peroxide -- toxicity KW - Nitrogen Oxides -- pharmacokinetics KW - Nitrogen Oxides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70819240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Cellular+sites+of+H2O2-induced+damage+and+their+protection+by+nitroxides.&rft.au=Samuni%2C+A+M%3BDeGraff%2C+W%3BKrishna%2C+M+C%3BMitchell%2C+J+B&rft.aulast=Samuni&rft.aufirst=A&rft.date=2001-02-16&rft.volume=1525&rft.issue=1-2&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depletion of systemic macrophages by liposome-encapsulated clodronate attenuates striatal macrophage invasion and neurodegeneration following local endotoxin infusion in gerbils. AN - 70629733; 11172745 AB - CNS-localized inflammation with microglial activation and macrophage infiltration contributes to the pathogenesis of a broad spectrum of neurologic diseases. A direct injection of lipopolysaccharide (LPS) into the striatum of gerbils induced lectin-positive macrophage parenchymal invasion, minimal local microglial staining but extensive neurodegeneration (cresyl violet and silver staining) when evaluated 4 days later. In mice, LPS activated microglia (increased lectin staining of morphologically identified cells) with substantially less macrophage invasion but no neurodegeneration was seen at 4 days post LPS infusion. To evaluate the role of infiltrating macrophages in the neurodegenerative response in gerbils, peripheral macrophages were depleted by an intravenous injection of liposome-encapsulated clodronate. This preparation depleted spleen and liver macrophages (>95%), decreased blood monocytes by 55% and attenuated striatal macrophage infiltration (32 to 73% in five representative sections). Notably, the liposome-encapsulated clodronate reduced the severity of LPS-induced neurodegeneration, as visualized by cresyl violet staining and quantified in 20 serially stained silver sections (total volume, 1.32+/-0.41 mm(3) in liposome-encapsulated clodronate-treated versus 3.04+/-0.72 mm(3) in saline-treated controls). These results indicate that a local LPS infusion in gerbil brain may be a useful model in which to investigate the role of invading macrophages and other inflammatory responses in neurodegeneration in inflammatory neurological disease. JF - Brain research AU - Zito, M A AU - Koennecke, L A AU - McAuliffe, M J AU - McNally, B AU - van Rooijen, N AU - Heyes, M P AD - Laboratory of Neurotoxicology, Building 10, Room 3D42, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2001/02/16/ PY - 2001 DA - 2001 Feb 16 SP - 13 EP - 26 VL - 892 IS - 1 SN - 0006-8993, 0006-8993 KW - Drug Carriers KW - 0 KW - Endotoxins KW - Lipopolysaccharides KW - Liposomes KW - Clodronic Acid KW - 0813BZ6866 KW - Index Medicus KW - Animals KW - Gerbillinae KW - Analysis of Variance KW - Leukocytes -- physiology KW - Endotoxins -- administration & dosage KW - Mice KW - Infusions, Parenteral KW - Leukocytes -- drug effects KW - Mice, Inbred C57BL KW - Salmonella KW - Endotoxins -- toxicity KW - Clodronic Acid -- pharmacology KW - Lipopolysaccharides -- administration & dosage KW - Macrophages -- pathology KW - Nerve Degeneration -- chemically induced KW - Macrophages -- physiology KW - Lipopolysaccharides -- toxicity KW - Corpus Striatum -- drug effects KW - Nerve Degeneration -- prevention & control KW - Clodronic Acid -- administration & dosage KW - Corpus Striatum -- pathology KW - Macrophages -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70629733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Depletion+of+systemic+macrophages+by+liposome-encapsulated+clodronate+attenuates+striatal+macrophage+invasion+and+neurodegeneration+following+local+endotoxin+infusion+in+gerbils.&rft.au=Zito%2C+M+A%3BKoennecke%2C+L+A%3BMcAuliffe%2C+M+J%3BMcNally%2C+B%3Bvan+Rooijen%2C+N%3BHeyes%2C+M+P&rft.aulast=Zito&rft.aufirst=M&rft.date=2001-02-16&rft.volume=892&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel host cell reactivation assay to assess homologous recombination capacity in human cancer cell lines. AN - 70595918; 11178982 AB - Repair of DNA double-strand breaks (DSB) is essential for cell viability and genome stability. Homologous recombination repair plays an important role in DSB repair and impairment of this repair mechanism may lead to loss of genomic integrity, which is one of the hallmarks of cancer. Recent research has shown that the tumor suppressor genes p53 and BRCA1 and -2 are involved in the proper control of homologous recombination, suggesting a role of this type of repair in human cancer. We developed a novel assay based on recombination between two Green Fluorescent Protein (GFP) sequences in transiently transfected plasmid DNA. The plasmid construct contains an intact, emission-shifted, "blue" variant of GFP (BFP), with a 300 nucleotide stretch of homology to a nonfunctional copy of GFP. In the absence of homologous recombination only BFP is present, but homologous recombination can create a functional GFP. The homologous regions in the plasmid were constructed in both the direct and the inverted orientation of transcription to detect possible differences in the recombination mechanisms involved. A panel of human tumor cell lines was chosen on the basis of genetic background and chromosome integrity and tested for homologous recombination using this assay. The panel included cell lines with varying levels of karyotypic abnormalities, isogenic cell lines with normal and mutant p53, isogenic cell lines with or without DNA mismatch repair, BRCA1 and -2 mutant cell lines, and the lymphoma cell line DT40. With this assay, the observed differences between cell lines with the lowest and highest levels of recombination were about 100-fold. Increased levels of recombination were associated with mutant p53, whereas a low level of recombination was found in the BRCA1 mutant cell line. In the cell line HT1080TG, a mutagenized derivative of HT1080 with two mutant alleles of p53, high levels of recombination were found with the direct orientation but not with the inverted orientation plasmid. No difference in recombination was detected between two isogenic cell lines that only differed in DNA mismatch repair capability. We conclude that this assay can detect differences in homologous recombination capacity in cultured cell lines and that these differences follow the patterns that would be expected from the different genotypes of these cell lines. Future application in normal cells may be useful to identify genetic determinants controlling genomic integrity or to detect differences in DNA repair capacity in individuals. JF - Biochemical and biophysical research communications AU - Slebos, R J AU - Taylor, J A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. slebos@niehs.nih.gov Y1 - 2001/02/16/ PY - 2001 DA - 2001 Feb 16 SP - 212 EP - 219 VL - 281 IS - 1 SN - 0006-291X, 0006-291X KW - Luminescent Proteins KW - 0 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Karyotyping KW - Plasmids -- metabolism KW - DNA Repair KW - Humans KW - Tumor Cells, Cultured KW - Transfection KW - Genes, BRCA1 -- genetics KW - Base Pair Mismatch KW - Models, Genetic KW - Genes, p53 -- genetics KW - Flow Cytometry KW - Luminescent Proteins -- genetics KW - Mutation KW - Recombination, Genetic KW - Molecular Biology -- methods KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70595918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=A+novel+host+cell+reactivation+assay+to+assess+homologous+recombination+capacity+in+human+cancer+cell+lines.&rft.au=Slebos%2C+R+J%3BTaylor%2C+J+A&rft.aulast=Slebos&rft.aufirst=R&rft.date=2001-02-16&rft.volume=281&rft.issue=1&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Invited commentary: studies of workers exposed to low doses of radiation. AN - 77065101; 11207147 JF - American journal of epidemiology AU - Gilbert, E S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. gilberte@mail.nih.gov Y1 - 2001/02/15/ PY - 2001 DA - 2001 Feb 15 SP - 319 EP - 22; discussion 323-4 VL - 153 IS - 4 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Canada -- epidemiology KW - Radiometry KW - Risk Factors KW - Humans KW - Health Personnel KW - Male KW - Female KW - Risk Assessment KW - Neoplasms, Radiation-Induced -- epidemiology KW - Occupational Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77065101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Invited+commentary%3A+studies+of+workers+exposed+to+low+doses+of+radiation.&rft.au=Gilbert%2C+E+S&rft.aulast=Gilbert&rft.aufirst=E&rft.date=2001-02-15&rft.volume=153&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-19 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Am J Epidemiol. 2001 Feb 15;153(4):309-18 [11207146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A model for the abrogation of the SOS response by an SOS protein: a negatively charged helix in DinI mimics DNA in its interaction with RecA. AN - 76968728; 11230150 AB - DinI is a recently described negative regulator of the SOS response in Escherichia coli. Here we show that it physically interacts with RecA and prevents the binding of single-stranded DNA to RecA, which is required for the activation of the latter. DinI also displaces ssDNA from a stable RecA-DNA cofilament, thus eliminating the SOS signal. In addition, DinI inhibits RecA-mediated homologous DNA pairing, but has no effect on actively proceeding strand exchange. Biochemical data, together with the molecular structure, define the C-terminal alpha-helix in DinI as the active site of the protein. In an unusual example of molecular mimicry, a negatively charged surface on this alpha-helix, by imitating single-stranded DNA, interacts with the loop L2 homologous pairing region of RecA and interferes with the activation of RecA. JF - Genes & development AU - Voloshin, O N AU - Ramirez, B E AU - Bax, A AU - Camerini-Otero, R D AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/02/15/ PY - 2001 DA - 2001 Feb 15 SP - 415 EP - 427 VL - 15 IS - 4 SN - 0890-9369, 0890-9369 KW - Bacterial Proteins KW - 0 KW - DNA Primers KW - DNA, Bacterial KW - DinI protein, E coli KW - Escherichia coli Proteins KW - Rec A Recombinases KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Bacterial Proteins -- genetics KW - SOS Response (Genetics) KW - DNA, Bacterial -- chemistry KW - Bacterial Proteins -- metabolism KW - Molecular Mimicry KW - Rec A Recombinases -- metabolism KW - DNA, Bacterial -- physiology KW - DNA, Bacterial -- metabolism KW - Bacterial Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76968728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=A+model+for+the+abrogation+of+the+SOS+response+by+an+SOS+protein%3A+a+negatively+charged+helix+in+DinI+mimics+DNA+in+its+interaction+with+RecA.&rft.au=Voloshin%2C+O+N%3BRamirez%2C+B+E%3BBax%2C+A%3BCamerini-Otero%2C+R+D&rft.aulast=Voloshin&rft.aufirst=O&rft.date=2001-02-15&rft.volume=15&rft.issue=4&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Microbiol Mol Biol Rev. 1999 Dec;63(4):751-813, table of contents [10585965] Science. 1999 Dec 17;286(5448):2349-52 [10600747] Nature. 2000 Mar 2;404(6773):37-41 [10716434] Mol Microbiol. 2000 Mar;35(6):1560-72 [10760155] J Mol Biol. 2000 Nov 10;303(5):709-20 [11061970] Protein Sci. 2000 Nov;9(11):2161-9 [11152126] Proc Natl Acad Sci U S A. 1980 May;77(5):2819-23 [6771759] J Biol Chem. 1986 May 25;261(15):6954-60 [3700423] J Mol Biol. 1988 Dec 20;204(4):959-72 [3065521] Biochimie. 1991 Apr;73(4):411-21 [1911941] EMBO J. 1991 Dec;10(13):4391-6 [1836761] Anal Biochem. 1991 Nov 1;198(2):268-77 [1724720] Annu Rev Biochem. 1992;61:603-40 [1497320] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5428-32 [8516284] Mol Gen Genet. 1995 Jul 22;248(1):103-13 [7651321] Eur J Biochem. 1995 Oct 15;233(2):419-25 [7588783] J Biol Chem. 1995 Dec 15;270(50):30230-3 [8530434] Mol Gen Genet. 1996 Apr 10;250(6):674-80 [8628227] Science. 1996 May 10;272(5263):868-72 [8629021] J Bacteriol. 1996 Jul;178(13):3854-9 [8682790] Annu Rev Genet. 1995;29:509-52 [8825485] Prog Nucleic Acid Res Mol Biol. 1997;56:129-223 [9187054] Science. 1997 Nov 7;278(5340):1111-4 [9353189] J Biol Chem. 1998 Mar 6;273(10):5708-15 [9488703] J Mol Biol. 1998 Mar 20;277(1):1-11 [9514744] EMBO J. 1998 Jun 1;17(11):3207-16 [9606202] Front Biosci. 1998 Jun 17;3:D570-603 [9632377] Nat Struct Biol. 1998 Dec;5(12):1065-74 [9846877] Mutagenesis. 1999 May;14(3):295-300 [10374997] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling through direct interaction with Smad4: potential mechanism of hepatitis B virus-induced liver fibrosis. AN - 76966953; 11230153 AB - Hepatitis B, one of the most common infectious diseases in the world, is closely associated with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Many clinical investigations have revealed that hepatic fibrosis is an important component of these liver diseases caused by chronic hepatitis B. TGF-beta signaling plays an important role in the pathogenesis of fibrosis in chronic hepatitis and cirrhosis. As these diseases are associated with hepatitis B virus (HBV) infection, we examined the possibility that the HBV-encoded pX oncoprotein regulates TGF-beta signaling. We show that pX enhances transcriptional activity in response to TGF-beta, BMP-2, and activin by stabilizing the complex of Smad4 with components of the basic transcriptional machinery. Additionally, confocal microscopic studies suggest that pX facilitates and potentiates the nuclear translocation of Smads, further enhancing TGF-beta signaling. Our studies suggest a new paradigm for amplification of Smad-mediated signaling by an oncoprotein and suggest that enhanced Smad-mediated signaling may contribute to HBV-associated liver fibrosis. JF - Genes & development AU - Lee, D K AU - Park, S H AU - Yi, Y AU - Choi, S G AU - Lee, C AU - Parks, W T AU - Cho, H AU - de Caestecker, M P AU - Shaul, Y AU - Roberts, A B AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2001/02/15/ PY - 2001 DA - 2001 Feb 15 SP - 455 EP - 466 VL - 15 IS - 4 SN - 0890-9369, 0890-9369 KW - DNA-Binding Proteins KW - 0 KW - Oncogene Proteins, Viral KW - Smad4 Protein KW - Smad4 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Cell Nucleus -- metabolism KW - Mice KW - Protein Binding KW - Transcriptional Activation KW - Trans-Activators -- metabolism KW - Signal Transduction -- physiology KW - Liver Cirrhosis -- virology KW - Hepatitis B virus -- pathogenicity KW - Oncogene Proteins, Viral -- genetics KW - Oncogene Proteins, Viral -- physiology KW - Hepatitis B virus -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Oncogene Proteins, Viral -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76966953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=The+hepatitis+B+virus+encoded+oncoprotein+pX+amplifies+TGF-beta+family+signaling+through+direct+interaction+with+Smad4%3A+potential+mechanism+of+hepatitis+B+virus-induced+liver+fibrosis.&rft.au=Lee%2C+D+K%3BPark%2C+S+H%3BYi%2C+Y%3BChoi%2C+S+G%3BLee%2C+C%3BParks%2C+W+T%3BCho%2C+H%3Bde+Caestecker%2C+M+P%3BShaul%2C+Y%3BRoberts%2C+A+B%3BKim%2C+S+J&rft.aulast=Lee&rft.aufirst=D&rft.date=2001-02-15&rft.volume=15&rft.issue=4&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1999 Oct 22;286(5440):771-4 [10531062] Oncogene. 1999 Feb 18;18(7):1495-501 [10050886] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2345-9 [10051644] Genes Dev. 1999 Sep 1;13(17):2196-206 [10485843] J Biol Chem. 1999 Oct 1;274(40):28716-23 [10497242] J Biol Chem. 1999 Dec 3;274(49):35269-77 [10575014] J Biol Chem. 1999 Dec 24;274(52):37105-10 [10601270] J Biol Chem. 2000 Mar 24;275(12):8825-34 [10722728] Genes Dev. 2000 Mar 15;14(6):627-44 [10733523] J Biol Chem. 2000 Aug 18;275(33):25858-64 [10835427] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Cell. 1989 Dec 22;59(6):1145-56 [2598264] Nature. 1990 Mar 1;344(6261):72-4 [2154703] Cell. 1990 Nov 16;63(4):687-95 [2225072] N Engl J Med. 1991 Apr 4;324(14):933-40 [1900574] Science. 1991 May 10;252(5007):842-4 [1827531] Nature. 1991 May 23;351(6324):317-20 [2034275] Hepatology. 1991 Aug;14(2):269-73 [1713566] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11332-6 [1454816] Cell. 1992 Dec 11;71(6):1003-14 [1333888] Nature. 1993 Feb 25;361(6414):742-5 [8441471] Lancet. 1993 Nov 27;342(8883):1335-40 [7901639] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2230-4 [8134379] J Virol. 1995 Mar;69(3):1851-9 [7853526] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1003-7 [7862623] Hepatology. 1995 Mar;21(3):760-6 [7875675] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2572-6 [7708687] J Clin Invest. 1996 Jan 15;97(2):388-95 [8567959] Cancer Res. 1996 Jun 1;56(11):2527-30 [8653691] EMBO J. 1996 Jul 1;15(13):3413-20 [8670843] Nature. 1996 Sep 12;383(6596):168-72 [8774881] Science. 1997 Jan 24;275(5299):523-7 [8999795] J Biol Chem. 1997 Mar 14;272(11):7132-9 [9054408] J Hepatol. 1997 Apr;26(4):886-93 [9126804] Cancer Res. 1997 Jul 15;57(14):2856-9 [9230189] Nature. 1997 Sep 4;389(6646):85-9 [9288972] Nature. 1997 Dec 4;390(6659):465-71 [9393997] Mol Cell Biol. 1998 Mar;18(3):1562-9 [9488473] Gastroenterology. 1998 Mar;114(3):550-8 [9496947] Hepatology. 1998 Apr;27(4):1109-20 [9537452] EMBO J. 1998 Jun 1;17(11):3091-100 [9606191] Mol Cell. 1998 Mar;1(4):611-7 [9660945] Nature. 1998 Jul 2;394(6688):92-6 [9665135] Genes Dev. 1998 Jul 15;12(14):2114-9 [9679056] Genes Dev. 1998 Jul 15;12(14):2153-63 [9679060] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9506-11 [9689110] J Biol Chem. 1998 Aug 14;273(33):21145-52 [9694870] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9785-90 [9707553] J Biol Chem. 1998 Sep 4;273(36):22865-8 [9722503] Cell. 1998 Dec 11;95(6):737-40 [9865691] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12442-7 [10535941] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leptin attenuates acute food deprivation-induced relapse to heroin seeking. AN - 70637554; 11160414 AB - Studies in rats have shown that intermittent footshock stress reinstates drug seeking after prolonged drug-free periods. Recently, we found that another environmental stressor, acute 1 d food deprivation, potently reinstates heroin seeking in rats. Here we report that this effect of food deprivation can be blocked by leptin, a hormone involved in the regulation of energy balance and food intake. Rats were trained to self-administer heroin (0.05-0.1 mg/kg, i.v., per infusion, three 3 hr sessions per day) for 8-10 d. The heroin-reinforced behavior was then extinguished for 10-13 d, during which lever presses had no reinforced consequences. Subsequently, rats were tested for reinstatement after 1 d of food deprivation (experiment 1) or exposure to intermittent footshock (15 min, 0.6 mA) and heroin priming injections (0.25 mg/kg, s.c.) (experiment 2). Acute food deprivation reinstated heroin seeking, an effect that was attenuated by leptin (2 or 4 microgram/rat, i.c.v.; two infusions, given 21 hr and 20-30 min before the start of the test sessions). In contrast, leptin had no effect on reinstatement of heroin seeking induced by intermittent footshock or priming injections of heroin. These data indicate that food deprivation can provoke relapse to heroin seeking via a leptin-dependent mechanism, which is not involved in relapse induced by footshock stress or reexposure to heroin. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Shalev, U AU - Yap, J AU - Shaham, Y AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse/Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2001/02/15/ PY - 2001 DA - 2001 Feb 15 SP - 1 VL - 21 IS - 4 KW - Leptin KW - 0 KW - Heroin KW - 70D95007SX KW - Index Medicus KW - Rats KW - Animals KW - Self Administration KW - Rats, Long-Evans KW - Treatment Outcome KW - Injections, Subcutaneous KW - Disease Models, Animal KW - Electroshock KW - Male KW - Heroin -- administration & dosage KW - Stress, Physiological -- physiopathology KW - Injections, Intraventricular KW - Behavior, Animal -- drug effects KW - Leptin -- administration & dosage KW - Heroin Dependence -- physiopathology KW - Heroin Dependence -- drug therapy KW - Food Deprivation KW - Secondary Prevention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70637554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Leptin+attenuates+acute+food+deprivation-induced+relapse+to+heroin+seeking.&rft.au=Shalev%2C+U%3BYap%2C+J%3BShaham%2C+Y&rft.aulast=Shalev&rft.aufirst=U&rft.date=2001-02-15&rft.volume=21&rft.issue=4&rft.spage=RC129&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel secondary Ig VH gene rearrangement and in-frame Ig heavy chain complementarity-determining region III insertion/deletion variants in de novo follicular lymphoma. AN - 70611956; 11160277 AB - Human germinal center B cell tumors retain the ability of their nontransformed counterparts to somatically hypermutate Ig V genes by nucleotide substitution. Among a survey of 60 primary previously untreated, clonal, follicular lymphomas we have identified a rare V(H) rearrangement variant and two other in-frame nucleotide insertion/deletion variants within complementarity-determining region III of the Ig heavy chain. The neoplastic origin of the V(H) rearrangement variant was directly demonstrated in cells isolated by microdissection from malignant follicles. In all three cases a common clonal origin for the variants was demonstrated by complementarity-determining region III nucleotide sequence homology and shared somatic mutations in germline encoded positions in framework region IV. The monoclonal nature of the tumors was independently confirmed by demonstrating a single t(14;18) translocation breakpoint in the two cases with a detectable translocation. All the variants occurred in functional V(H) rearrangements, which in two cases were directly shown to encode functional Ab molecules. Both recombination-activating genes 1 and 2 were expressed in lymph node tumor cells containing the V(H) rearrangement variant, although recombination-activating gene expression among a panel of lymphomas was not limited to this variant. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kobrin, C AU - Bendandi, M AU - Kwak, L AD - Intramural Research Support Program, Science Applications International Corp.-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 2001/02/15/ PY - 2001 DA - 2001 Feb 15 SP - 2235 EP - 2243 VL - 166 IS - 4 SN - 0022-1767, 0022-1767 KW - Complementarity Determining Regions KW - 0 KW - DNA-Binding Proteins KW - Homeodomain Proteins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin J-Chains KW - Immunoglobulin Variable Region KW - Nuclear Proteins KW - RAG2 protein, human KW - RNA, Messenger KW - V(D)J recombination activating protein 2 KW - RAG-1 protein KW - 128559-51-3 KW - Transposases KW - EC 2.7.7.- KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - B-Lymphocytes -- pathology KW - Homeodomain Proteins -- biosynthesis KW - Humans KW - DNA-Binding Proteins -- biosynthesis KW - DNA-Binding Proteins -- genetics KW - Genes, Immunoglobulin KW - Cell Separation KW - B-Lymphocytes -- metabolism KW - RNA, Messenger -- biosynthesis KW - Gene Amplification KW - Genetic Variation -- immunology KW - Homeodomain Proteins -- genetics KW - Molecular Sequence Data KW - Chromosomes, Human, Pair 18 -- immunology KW - Chromosomes, Human, Pair 14 -- genetics KW - Immunoglobulin Variable Region -- genetics KW - DNA Fingerprinting KW - Chromosomes, Human, Pair 18 -- genetics KW - B-Lymphocytes -- immunology KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Translocation, Genetic KW - Base Sequence KW - Chromosomes, Human, Pair 14 -- immunology KW - Transposases -- genetics KW - Immunoglobulin J-Chains -- genetics KW - Sequence Deletion -- immunology KW - Lymphoma, Follicular -- genetics KW - Lymphoma, Follicular -- pathology KW - Mutagenesis, Insertional -- immunology KW - Complementarity Determining Regions -- genetics KW - Gene Rearrangement, B-Lymphocyte, Heavy Chain KW - Reading Frames -- immunology KW - Reading Frames -- genetics KW - Immunoglobulin Heavy Chains -- genetics KW - Complementarity Determining Regions -- biosynthesis KW - Lymphoma, Follicular -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70611956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Novel+secondary+Ig+VH+gene+rearrangement+and+in-frame+Ig+heavy+chain+complementarity-determining+region+III+insertion%2Fdeletion+variants+in+de+novo+follicular+lymphoma.&rft.au=Kobrin%2C+C%3BBendandi%2C+M%3BKwak%2C+L&rft.aulast=Kobrin&rft.aufirst=C&rft.date=2001-02-15&rft.volume=166&rft.issue=4&rft.spage=2235&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distribution of Streptococcal Inhibitor of Complement Variants in Pharyngitis and Invasive Isolates in an Epidemic of Serotype M1 Group A Streptococcus Infection AN - 18075342; 5149700 AB - Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made predominantly by serotype M1 group A Streptococcus (GAS). New variants of the Sic protein frequently appear in M1 epidemics as a result of positive natural selection. To gain further understanding of the molecular basis of M1 epidemics, the sic gene was sequenced from 471 pharyngitis and 127 pyogenic and blood isolates recovered from 598 patients living in metropolitan Helsinki, Finland, during a 37-month population-based surveillance study. Most M1 GAS subclones recovered from pyogenic infections and blood were abundantly represented in the pool of subclones causing pharyngitis. Alleles shared among the pharyngitis, pyogenic, and blood samples were identified in throat isolates a mean of 9.8 months before their recovery from pyogenic infections and blood, which indicates that selection of most sic variants occurs on mucosal surfaces. In contrast, no variation was identified in the emm and covR/covS genes. JF - Journal of Infectious Diseases AU - Hoe, N P AU - Vuopio-Varkila, J AU - Vaara, M AU - Grigsby, D AU - De Lorenzo, D AU - Fu, Y-X AU - Dou, S-J AU - Pan, X AU - Nakashima, K AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2001/02/15/ PY - 2001 DA - 2001 Feb 15 SP - 633 EP - 639 VL - 183 IS - 4 SN - 0022-1899, 0022-1899 KW - Sic protein KW - Microbiology Abstracts B: Bacteriology KW - Complement KW - Inhibitors KW - Pharyngitis KW - Streptococcus pyogenes KW - J 02845:Ear, nose and respiratory tract KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18075342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Distribution+of+Streptococcal+Inhibitor+of+Complement+Variants+in+Pharyngitis+and+Invasive+Isolates+in+an+Epidemic+of+Serotype+M1+Group+A+Streptococcus+Infection&rft.au=Hoe%2C+N+P%3BVuopio-Varkila%2C+J%3BVaara%2C+M%3BGrigsby%2C+D%3BDe+Lorenzo%2C+D%3BFu%2C+Y-X%3BDou%2C+S-J%3BPan%2C+X%3BNakashima%2C+K%3BMusser%2C+J+M&rft.aulast=Hoe&rft.aufirst=N&rft.date=2001-02-15&rft.volume=183&rft.issue=4&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Pharyngitis; Complement; Inhibitors ER - TY - JOUR T1 - Mutagenesis of the regulatory domain of phenylalanine hydroxylase. AN - 70636472; 11171986 AB - The regulatory domain of phenylalanine hydroxylase (PAH, EC ) consists of more than 100 amino acids at the N terminus, the removal of which significantly activates the enzyme. To study the regulatory properties controlled by the N terminus, a series of truncations and site-specific mutations were made in this region of rat PAH. These enzymes were expressed highly in Escherichia coli and purified through a pterin-conjugated Sepharose affinity column. The removal of the first 26 amino acids of the N terminus increased the activity by about 20-fold, but removal of the first 15 amino acids increased the activity by only 2-fold. Replacing serine-29 of rat PAH with cysteine from the same site of human PAH increased the activity by more than 4-fold. Mutation of serine to other amino acids with varying side chains: alanine, methionine, leucine, aspartic acid, asparagine, and arginine also resulted in significant activation, indicating a serine-specific inhibitory effect. But these site-specific mutants showed 30--40% lower activity when assayed with 6-methyl-5,6,7,8-tetrahydropterin. Stimulation of hydroxylase activity by preincubation of the enzyme with phenylalanine was inversely proportional to the activation state of all these mutants. Combined with recent crystal structures of PAH [Kobe, B. et al. (1999) Nat. Struct. Biol. 6, 442-448; and Erlandsen, H., Bjorgo, E., Flatmark, T. & Stevens, R. C. (2000) Biochemistry 39, 2208-2217], these data suggest that residues 16-26 have a controlling regulatory effect on the activity by interaction with the dihydroxypropyl side chain of (6R)-5,6,7,8-tetrahydrobiopterin. The serine/cysteine switch explains the difference in regulatory properties between human and rat PAH. The N terminus as a whole is important for maintaining rat PAH in an optimum catalytic conformation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wang, G A AU - Gu, P AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, Building 36, Room 3D30, Bethesda, MD 20892, USA. gawang@mit.edu Y1 - 2001/02/13/ PY - 2001 DA - 2001 Feb 13 SP - 1537 EP - 1542 VL - 98 IS - 4 SN - 0027-8424, 0027-8424 KW - Serine KW - 452VLY9402 KW - Phenylalanine KW - 47E5O17Y3R KW - Phenylalanine Hydroxylase KW - EC 1.14.16.1 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Cysteine -- metabolism KW - Phenylalanine -- metabolism KW - Cysteine -- genetics KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - Serine -- metabolism KW - Cysteine -- physiology KW - Serine -- genetics KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Kinetics KW - Serine -- physiology KW - Molecular Sequence Data KW - Amino Acid Substitution KW - Phenylalanine Hydroxylase -- isolation & purification KW - Phenylalanine Hydroxylase -- physiology KW - Phenylalanine Hydroxylase -- genetics KW - Phenylalanine Hydroxylase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70636472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Mutagenesis+of+the+regulatory+domain+of+phenylalanine+hydroxylase.&rft.au=Wang%2C+G+A%3BGu%2C+P%3BKaufman%2C+S&rft.aulast=Wang&rft.aufirst=G&rft.date=2001-02-13&rft.volume=98&rft.issue=4&rft.spage=1537&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1984 Feb 25;259(4):2474-9 [6698976] J Biol Chem. 1957 May;226(1):511-24 [13428782] J Biol Chem. 1984 Dec 10;259(23):14560-6 [6501308] J Biol Chem. 1986 Feb 15;261(5):2051-6 [3944127] Adv Enzyme Regul. 1986;25:37-64 [3028051] Methods Enzymol. 1987;142:3-17 [3600372] Methods Enzymol. 1987;142:83-7 [3600387] Biochemistry. 1991 Jul 9;30(27):6795-802 [2065060] Protein Expr Purif. 1992 Apr;3(2):93-100 [1422220] Hum Mutat. 1992;1(2):147-53 [1301201] J Biol Chem. 1994 Aug 12;269(32):20369-75 [7914195] Biochem J. 1995 Mar 1;306 ( Pt 2):589-97 [7887915] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4743-7 [7761394] Biochem J. 1995 Oct 15;311 ( Pt 2):353-66 [7487868] Arch Biochem Biophys. 1996 Sep 1;333(1):85-95 [8806757] Eur J Biochem. 1996 Dec 15;242(3):813-21 [9022714] Nat Struct Biol. 1997 Dec;4(12):995-1000 [9406548] Nat Struct Biol. 1999 May;6(5):442-8 [10331871] Biochemistry. 2000 Mar 7;39(9):2208-17 [10694386] J Biol Chem. 1972 Apr 10;247(7):2250-2 [5062822] J Biol Chem. 1973 Jun 25;248(12):4345-53 [4145799] FEBS Lett. 1974 Aug 30;44(3):290-2 [4212894] Eur J Biochem. 1978 Apr 17;85(2):357-63 [648526] J Biochem. 1981 Aug;90(2):567-9 [7298604] J Biol Chem. 1982 Mar 25;257(6):3084-9 [7061466] Mol Genet Metab. 1999 Oct;68(2):103-25 [10527663] Biochemistry. 1984 Aug 14;23(17):3836-42 [6487579] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma membrane depolarization without repolarization is an early molecular event in anti-Fas-induced apoptosis. AN - 70864333; 11050080 AB - The movement of intracellular monovalent cations has previously been shown to play a critical role in events leading to the characteristics associated with apoptosis. A loss of intracellular potassium and sodium occurs during apoptotic cell shrinkage establishing an intracellular environment favorable for nuclease activity and caspase activation. We have now investigated the potential movement of monovalent ions in Jurkat cells that occur prior to cell shrinkage following the induction of apoptosis. A rapid increase in intracellular sodium occurs early after apoptotic stimuli suggesting that the normal negative plasma membrane potential may change during cell death. We report here that diverse apoptotic stimuli caused a rapid cellular depolarization of Jurkat T-cells that occurs prior to and after cell shrinkage. In addition to the early increase in intracellular Na(+), (86)Rb(+) studies reveal a rapid inhibition of K(+) uptake in response to anti-Fas. These effects on Na(+) and K(+) ions were accounted for by the inactivation of the Na(+)/K(+)-ATPase protein and its activity. Furthermore, ouabain, a cardiac glycoside inhibitor of the Na(+)/K(+)-ATPase, potentiated anti-Fas-induced apoptosis. Finally, activation of an anti-apoptotic signal, i.e. protein kinase C, prevented both cellular depolarization in response to anti-Fas and all downstream characteristics associated with apoptosis. Thus cellular depolarization is an important early event in anti-Fas-induced apoptosis, and the inability of cells to repolarize via inhibition of the Na(+)/K(+)-ATPase is a likely regulatory component of the death process. JF - The Journal of biological chemistry AU - Bortner, C D AU - Gomez-Angelats, M AU - Cidlowski, J A AD - Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/02/09/ PY - 2001 DA - 2001 Feb 09 SP - 4304 EP - 4314 VL - 276 IS - 6 SN - 0021-9258, 0021-9258 KW - Antibodies KW - 0 KW - Antigens, CD95 KW - Sodium KW - 9NEZ333N27 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Sodium-Potassium-Exchanging ATPase -- antagonists & inhibitors KW - Cell Membrane -- drug effects KW - Humans KW - Jurkat Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- physiology KW - Cell Membrane -- metabolism KW - Sodium -- metabolism KW - Antibodies -- immunology KW - Apoptosis -- immunology KW - Membrane Potentials KW - Antigens, CD95 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70864333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Plasma+membrane+depolarization+without+repolarization+is+an+early+molecular+event+in+anti-Fas-induced+apoptosis.&rft.au=Bortner%2C+C+D%3BGomez-Angelats%2C+M%3BCidlowski%2C+J+A&rft.aulast=Bortner&rft.aufirst=C&rft.date=2001-02-09&rft.volume=276&rft.issue=6&rft.spage=4304&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The dimerization motif of cytosolic sulfotransferases. AN - 70622513; 11172807 AB - Cytosolic sulfotransferases sulfate steroids such as estrogens and hydroxysteroids. The enzymes, including human estrogen sulfotransferase (hEST) and hydroxysteroid sulfotransferase (hHST), are generally homodimers in solution with mouse estrogen sulfotransferase (mEST) being one of few exceptions. To identify the amino acid residues responsible for the dimerization, eight residues on the surface of hEST were mutated to their counterparts in mEST and mutated hESTs were then analyzed by gel filtration chromatography. A single mutation of Val(269) to Glu was sufficient to convert hEST to a monomer and the corresponding mutation of Val(260) also altered hHST to a monomer. The hHST crystal structure revealed a short stretch of peptide with the side-chains from two hHST monomers forming a hydrophobic zipper-like structure enforced by ion pairs at both ends. This peptide consisted of 10 residues near the C-terminus that, including the critical Val residue, is conserved as KXXXTVXXXE in nearly all cytosolic sulfotransferases. When mEST underwent the double mutations Pro269Thr/Glu270Val dimerization resulted. Thus, the KXXXTVXXXE sequence appears to be the common protein-protein interaction motif that mediates the homo- as well as heterodimerization of cytosolic sulfotransferases. JF - FEBS letters AU - Petrotchenko, E V AU - Pedersen, L C AU - Borchers, C H AU - Tomer, K B AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS/NIH, Research Triangle Park, NC 27709, USA. Y1 - 2001/02/09/ PY - 2001 DA - 2001 Feb 09 SP - 39 EP - 43 VL - 490 IS - 1-2 SN - 0014-5793, 0014-5793 KW - Cross-Linking Reagents KW - 0 KW - Glutamine KW - 0RH81L854J KW - Sepharose KW - 9012-36-6 KW - Sulfotransferases KW - EC 2.8.2.- KW - Glutathione KW - GAN16C9B8O KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Animals KW - Mass Spectrometry KW - Plasmids -- metabolism KW - Models, Molecular KW - Electrophoresis, Polyacrylamide Gel KW - DNA Mutational Analysis KW - Glutathione -- metabolism KW - Humans KW - Cross-Linking Reagents -- metabolism KW - Mice KW - Amino Acid Sequence KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Sepharose -- metabolism KW - Amino Acid Motifs KW - Chromatography, Gel KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Molecular Sequence Data KW - Glutamine -- chemistry KW - Crystallography, X-Ray KW - Mutation KW - Valine -- chemistry KW - Sulfotransferases -- metabolism KW - Sulfotransferases -- chemistry KW - Dimerization KW - Cytosol -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70622513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=The+dimerization+motif+of+cytosolic+sulfotransferases.&rft.au=Petrotchenko%2C+E+V%3BPedersen%2C+L+C%3BBorchers%2C+C+H%3BTomer%2C+K+B%3BNegishi%2C+M&rft.aulast=Petrotchenko&rft.aufirst=E&rft.date=2001-02-09&rft.volume=490&rft.issue=1-2&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation. AN - 77072125; 11314000 AB - Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression of Pdcd4 protein is sufficient to suppress neoplastic transformation. To determine whether Pdcd4 suppresses neoplastic transformation through inhibiting known transformation required events, we examined the possibility that pdcd4 inhibited the activation of AP-1 or NF-kappaB dependent transcription or of ornithine decarboxylase (ODC) activity. Activation of AP-1-dependent transcriptional activity was inhibited by pdcd4 expression in a concentration dependent manner. In contrast, Pdcd4 slightly increased NF-kappaB-dependent transcription and did not alter ODC enzymatic activity. Previous studies suggested that activation of AP-1 was required for P+ cell transformation as well as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a transformation suppressor, possibly through inhibiting AP-1 activation in combination with other factors such as enhancing NF-kappaB activation. Pdcd4 may thus constitute a useful molecular target for cancer prevention. JF - Oncogene AU - Yang, H S AU - Jansen, A P AU - Nair, R AU - Shibahara, K AU - Verma, A K AU - Cmarik, J L AU - Colburn, N H AD - Gene Regulation Section, Basic Research Laboratory, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/02/08/ PY - 2001 DA - 2001 Feb 08 SP - 669 EP - 676 VL - 20 IS - 6 SN - 0950-9232, 0950-9232 KW - Apoptosis Regulatory Proteins KW - 0 KW - NF-kappa B KW - Pdcd4 protein, mouse KW - Proteins KW - RNA-Binding Proteins KW - Transcription Factor AP-1 KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Mice KW - Transcriptional Activation KW - Ornithine Decarboxylase -- genetics KW - Transcription Factor AP-1 -- metabolism KW - Genes, Tumor Suppressor KW - Proteins -- metabolism KW - Cell Transformation, Neoplastic -- genetics KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77072125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=A+novel+transformation+suppressor%2C+Pdcd4%2C+inhibits+AP-1+transactivation+but+not+NF-kappaB+or+ODC+transactivation.&rft.au=Yang%2C+H+S%3BJansen%2C+A+P%3BNair%2C+R%3BShibahara%2C+K%3BVerma%2C+A+K%3BCmarik%2C+J+L%3BColburn%2C+N+H&rft.aulast=Yang&rft.aufirst=H&rft.date=2001-02-08&rft.volume=20&rft.issue=6&rft.spage=669&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathiolation of proteins by glutathione disulfide S-oxide derived from S-nitrosoglutathione. Modifications of rat brain neurogranin/RC3 and neuromodulin/GAP-43. AN - 70886638; 11060308 AB - S-Nitrosoglutathione (GSNO) undergoes spontaneous degradation that generates several nitrogen-containing compounds and oxidized glutathione derivatives. We identified glutathione sulfonic acid, glutathione disulfide S-oxide (GS(O)SG), glutathione disulfide S-dioxide, and GSSG as the major decomposition products of GSNO. Each of these compounds and GSNO were tested for their efficacies to modify rat brain neurogranin/RC3 (Ng) and neuromodulin/GAP-43 (Nm). Among them, GS(O)SG was found to be the most potent in causing glutathiolation of both proteins; four glutathiones were incorporated into the four Cys residues of Ng, and two were incorporated into the two Cys residues of Nm. Ng and Nm are two in vivo substrates of protein kinase C; their phosphorylations by protein kinase C attenuate the binding affinities of both proteins for calmodulin. When compared with their respective unmodified forms, the glutathiolated Ng was a poorer substrate and glutathiolated Nm a better substrate for protein kinase C. Glutathiolation of these two proteins caused no change in their binding affinities for calmodulin. Treatment of [(35)S]cysteine-labeled rat brain slices with xanthine/xanthine oxidase or a combination of xanthine/xanthine oxidase with sodium nitroprusside resulted in an increase in cellular level of GS(O)SG. These treatments, as well as those by other oxidants, all resulted in an increase in thiolation of proteins; among them, thiolation of Ng was positively identified by immunoprecipitation. These results show that GS(O)SG is one of the most potent glutathiolating agents generated upon oxidative stress. JF - The Journal of biological chemistry AU - Li, J AU - Huang, F L AU - Huang, K P AD - Section on Metabolic Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 2001/02/02/ PY - 2001 DA - 2001 Feb 02 SP - 3098 EP - 3105 VL - 276 IS - 5 SN - 0021-9258, 0021-9258 KW - Calmodulin KW - 0 KW - Calmodulin-Binding Proteins KW - GAP-43 Protein KW - Nerve Tissue Proteins KW - Nitroso Compounds KW - Nrgn protein, rat KW - Oxidants KW - Proteins KW - Neurogranin KW - 132654-77-4 KW - S-Nitrosoglutathione KW - 57564-91-7 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Glutathione KW - GAN16C9B8O KW - Glutathione Disulfide KW - ULW86O013H KW - Index Medicus KW - Calmodulin -- metabolism KW - Animals KW - Oxidants -- pharmacology KW - Glutathione Disulfide -- metabolism KW - Brain -- metabolism KW - Precipitin Tests KW - Rats KW - Protein Kinase C -- metabolism KW - Oxidation-Reduction KW - GAP-43 Protein -- metabolism KW - Rats, Sprague-Dawley KW - Phosphorylation KW - In Vitro Techniques KW - Male KW - Nitroso Compounds -- metabolism KW - Glutathione -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - Calmodulin-Binding Proteins -- metabolism KW - Proteins -- metabolism KW - Glutathione -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70886638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Glutathiolation+of+proteins+by+glutathione+disulfide+S-oxide+derived+from+S-nitrosoglutathione.+Modifications+of+rat+brain+neurogranin%2FRC3+and+neuromodulin%2FGAP-43.&rft.au=Li%2C+J%3BHuang%2C+F+L%3BHuang%2C+K+P&rft.aulast=Li&rft.aufirst=J&rft.date=2001-02-02&rft.volume=276&rft.issue=5&rft.spage=3098&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular phylogenetics and the origins of placental mammals AN - 856754111; 13742976 AB - The precise hierarchy of ancient divergence events that led to the present assemblage of modern placental mammals has been an area of controversy among morphologists, palaeontologists and molecular evolutionists. Here we address the potential weaknesses of limited character and taxon sampling in a comprehensive molecular phylogenetic analysis of 64 species sampled across all extant orders of placental mammals. We examined sequence variation in 18 homologous gene segments (including nearly 10,000 base pairs) that were selected for maximal phylogenetic informativeness in resolving the hierarchy of early mammalian divergence. Phylogenetic analyses identify four primary superordinal clades: (I) Afrotheria (elephants, manatees, hyraxes, tenrecs, aardvark and elephant shrews); (II) Xenarthra (sloths, anteaters and armadillos); (III) Glires (rodents and lagomorphs), as a sister taxon to primates, flying lemurs and tree shrews; and (IV) the remaining orders of placental mammals (cetaceans, artiodactyls, perissodactyls, carnivores, pangolins, bats and core insectivores). Our results provide new insight into the pattern of the early placental mammal radiation. JF - Nature AU - Murphy, William J AU - Eizirik, Eduardo AU - Johnson, Warren E AU - Zhang, Ya Ping AU - Ryder, Oliver A AU - O'Brien, Stephen J AD - [1] Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, USA [2] These authors contributed equally to this work Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 614 EP - 618 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 409 IS - 6820 SN - 0028-0836, 0028-0836 KW - Genetics Abstracts; Oceanic Abstracts; ASFA 1: Biological Sciences & Living Resources; Sustainability Science Abstracts; Aqualine Abstracts; Water Resources Abstracts KW - Lemur KW - Mammals KW - Trees KW - Nucleotide sequence KW - Radiation KW - Cores KW - Tupaia KW - Placenta KW - Sampling KW - Armadillo KW - Rodents KW - Phylogenetics KW - Afrotheria KW - mammals KW - Phylogeny KW - Marine KW - carnivores KW - Flying KW - Carnivores KW - Bases KW - Primates KW - Xenarthra KW - Marine mammals KW - Insectivores KW - Taxonomy KW - Cetacea KW - insectivores KW - Aquatic mammals KW - rodents KW - Evolution KW - AQ 00001:Water Resources and Supplies KW - G 07810:Insects KW - M3 1010:Issues in Sustainable Development KW - O 1050:Vertebrates, Urochordates and Cephalochordates KW - SW 0540:Properties of water KW - Q1 08187:Palaeontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856754111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Molecular+phylogenetics+and+the+origins+of+placental+mammals&rft.au=Murphy%2C+William+J%3BEizirik%2C+Eduardo%3BJohnson%2C+Warren+E%3BZhang%2C+Ya+Ping%3BRyder%2C+Oliver+A%3BO%27Brien%2C+Stephen+J&rft.aulast=Murphy&rft.aufirst=William&rft.date=2001-02-01&rft.volume=409&rft.issue=6820&rft.spage=614&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35054550 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2016-02-18 N1 - SubjectsTermNotLitGenreText - Nucleotide sequence; Flying; Marine mammals; Carnivores; Taxonomy; Aquatic mammals; Evolution; Phylogenetics; Phylogeny; Cores; Radiation; Placenta; Insectivores; Sampling; mammals; Trees; carnivores; Primates; insectivores; rodents; Mammals; Bases; Rodents; Lemur; Xenarthra; Tupaia; Cetacea; Armadillo; Afrotheria; Marine DO - http://dx.doi.org/10.1038/35054550 ER - TY - JOUR T1 - Interaction of Semantic and Perceptual Processes in Repetition Blindness AN - 85524937; 200110589 AB - Two experiments examined the effect of activation of higher-level semantic representations on lower-level perceptual representations. A forced-choice discrimination paradigm was used, a method known to produce repetition blindness (RB) for words unconfounded by memory demands or response bias. In Experiment 1, equivalent reductions in RB occurred when successive word pairs were identical in: (1) form, pronunciation, & meaning (both uppercase versions of the same word); (2) pronunciation & meaning but not form (lowercase versus uppercase; lexical identity); & (3) pronunciation, but not form or meaning (homonyms; phonological identity), relative to when the words were unrelated on all dimensions. The RB effect was markedly attenuated, but not eliminated, when the words were semantically related. Similar results were obtained in Experiment 2 using a larger group of subjects. These findings show that higher-order semantic representations can have a top-down influence on judgments based on lower-order perceptual representations. The results are discussed within the framework of a cascade model of object processing in the human brain. 3 Tables, 2 Figures, 44 References. Adapted from the source document JF - Visual Cognition AU - Parasuraman, Raja AU - Martin, Alex AD - c/o Martin-National Instit Mental Health, Bethesda, MD alex@codon.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 103 EP - 118 VL - 8 IS - 1 SN - 1350-6285, 1350-6285 KW - Judgment (39900) KW - Brain (09350) KW - Perception (63450) KW - Semantic Processing (76760) KW - article KW - 4014: psycholinguistics; semantic processing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85524937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Visual+Cognition&rft.atitle=Interaction+of+Semantic+and+Perceptual+Processes+in+Repetition+Blindness&rft.au=Parasuraman%2C+Raja%3BMartin%2C+Alex&rft.aulast=Parasuraman&rft.aufirst=Raja&rft.date=2001-02-01&rft.volume=8&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Visual+Cognition&rft.issn=13506285&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - VICOF6 N1 - SubjectsTermNotLitGenreText - Semantic Processing (76760); Perception (63450); Judgment (39900); Brain (09350) ER - TY - JOUR T1 - Immortalization of rat middle ear epithelial cells by adeno 12-SV40 hybrid virus. AN - 85350638; pmid-11219520 AB - Rat middle ear epithelial cells were infected with the adeno 12-SV40 hybrid virus. The cell line thus obtained displays features of primary cultured epithelial cells in both light microscopic and ultrastructural examinations. The immortalized cells have been in continuous proliferation for 40 passages and more than 17 months. Immunohistochemical analysis of the immortalized cells was positive for the SV40 T antigen and the tumor suppressor protein p53. The cells also stained positive for cytokeratin, an epithelial cell marker, and negative for vimentin, a fibroblast marker. These results, together with karyotype analysis, indicate that this cell line originated from rat middle ear epithelial cells and retains the characteristics of epithelial cells. This cell line will be useful for studying the normal cellular biology of middle ear epithelial cells, as well as the cellular and molecular mechanisms involved in the bacteria-middle ear epithelial cell interaction. JF - The Annals of otology, rhinology, and laryngology AU - Ueyama, S AU - Jin, S AU - Rhim, J S AU - Ueyama, T AU - Lim, D J AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA. Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 132 EP - 141 VL - 110 IS - 2 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Animals KW - Antigens, Polyomavirus Transforming: analysis KW - Blotting, Western KW - *Cell Culture Techniques: methods KW - *Cell Line: physiology KW - *Cell Line: virology KW - *Disease Models, Animal KW - *Ear, Middle: cytology KW - *Epithelium: physiology KW - *Epithelium: ultrastructure KW - Immunohistochemistry KW - Karyotyping KW - Keratins: analysis KW - Male KW - Microscopy, Electron, Scanning KW - Otitis Media: etiology KW - Rats KW - Rats, Wistar KW - *Simian virus 40: physiology KW - Tumor Suppressor Protein p53: analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85350638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Immortalization+of+rat+middle+ear+epithelial+cells+by+adeno+12-SV40+hybrid+virus.&rft.au=Ueyama%2C+S%3BJin%2C+S%3BRhim%2C+J+S%3BUeyama%2C+T%3BLim%2C+D+J&rft.aulast=Ueyama&rft.aufirst=S&rft.date=2001-02-01&rft.volume=110&rft.issue=2&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Concurrent paclitaxel and radiation in the treatment of locally advanced head and neck cancer. AN - 85270634; pmid-11157034 AB - PURPOSE: To determine the feasibility of an organ preservation regimen consisting of infusional paclitaxel administered concurrently with radiotherapy to patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Thirty-three previously untreated patients with stage III or IV tumors were enrolled onto the study. Paclitaxel was administered as a 120-hour continuous infusion every 3 weeks during the course of radiation therapy. Sixteen patients received a paclitaxel dose of 105 mg/m(2), and 17 patients received 120 mg/m(2). Radiation was delivered in a standard format at 1.8 Gy/d to a total dose of 70.2 to 72 Gy. RESULTS: Three months after therapy, a 76% complete response (CR) at the primary site and a 70% overall CR was achieved. At 36 months, locoregional control was 55.7%, overall survival was 57.8%, and disease-free survival was 51.1%. The median survival duration for all 33 patients was greater than 50 months at the time of this report. Local toxicities including mucositis, dysphagia, and skin reactions were severe but tolerable. All patients retained functional speech, and all but four patients were swallowing food 3 months after treatment. Steady-state plasma concentrations for paclitaxel were not achieved during a 120-hour infusion, suggesting a nonlinear process. Tumor volume quantified by pretreatment computerized tomography imaging was associated with likelihood of response and survival. CONCLUSION: Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC. JF - Journal of Clinical Oncology AU - Sunwoo, J B AU - Herscher L L AU - Kroog, G S AU - Thomas, G R AU - Ondrey, F G AU - Duffey, D C AU - Solomon, B I AU - Boss, C AU - Albert, P S AU - McCullugh, L AU - Rudy, S AU - Muir, C AU - Zhai, S AU - Figg, W D AU - Cook, J A AU - Mitchell, J B AU - Van Waes C AD - Head and Neck Surgery Branch, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2001 SP - 800 EP - 811 VL - 19 IS - 3 SN - 0732-183X, 0732-183X KW - Disease-Free Survival KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Combined Modality Therapy KW - Human KW - Aged KW - Pilot Projects KW - Deglutition KW - Prospective Studies KW - Survival Rate KW - Radiation-Sensitizing Agents KW - Paclitaxel KW - Head and Neck Neoplasms KW - Adult KW - Middle Age KW - Carcinoma, Squamous Cell KW - Cell Cycle KW - Antineoplastic Agents, Phytogenic KW - Speech KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85270634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Oncology&rft.atitle=Concurrent+paclitaxel+and+radiation+in+the+treatment+of+locally+advanced+head+and+neck+cancer.&rft.au=Sunwoo%2C+J+B%3BHerscher+L+L%3BKroog%2C+G+S%3BThomas%2C+G+R%3BOndrey%2C+F+G%3BDuffey%2C+D+C%3BSolomon%2C+B+I%3BBoss%2C+C%3BAlbert%2C+P+S%3BMcCullugh%2C+L%3BRudy%2C+S%3BMuir%2C+C%3BZhai%2C+S%3BFigg%2C+W+D%3BCook%2C+J+A%3BMitchell%2C+J+B%3BVan+Waes+C&rft.aulast=Sunwoo&rft.aufirst=J&rft.date=2001-02-01&rft.volume=19&rft.issue=3&rft.spage=800&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of iodine on inducible nitric oxide synthase and cyclooxygenase-2 expression in sulfur mustard-induced skin. AN - 77059211; 11305779 AB - In a previous study we demonstrated the protective effect of topical iodine as postexposure treatment for sulfur mustard (SM) application. The iodine treatment results in significantly reduced inflammation and necrosis and increased epidermal hyperplasia. The expression and localization of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in paraffin-embedded skin samples from that study were evaluated in the present investigation. We compared the immunoreactivity of iNOS and COX-2 using five samples from each of the following four test sites: untreated control sites, SM-exposed sites, sites treated with iodine mixture 15 min after SM exposure, and sites treated with iodine 30 min after SM exposure. All animals were killed 2 days after irritant exposure. iNOS immunoreactivity was present only in skin sites exposed to SM without iodine treatment. The ulcerated skin was covered with a relatively thick band of exudate composed of iNOS-immunostained polymorphonuclear cells and macrophages. In untreated skin, COX-2 immunostaining was limited to the thin suprabasal epidermal layer. In SM-exposed skin, induction of COX-2 was noted in inflammatory cells located close to the site of epidermal injury. In skin sites treated with iodine 15 or 30 min after SM exposure, the regenerating hyperplastic epithelium showed moderate cytoplasmic staining localized to the epithelium overlying the basal layer. This pattern of staining was also present in the nearby dermal fibroblasts. Thus, in contrast to the skin samples exposed to SM without iodine treatment, the epidermal layer expressing immunohistochemical positivity for COX-2 was thicker and corresponded to the epidermal hyperplasia noted in samples treated with iodine. It is well documented that prostaglandins (PGs) promote epidermal proliferation, thereby contributing to the repair of injured skin. That the induction of the COX-2 shown in our study may also play a role in the healing process is indicated by the present evidence. The results suggest that nitric oxide radicals (NO*) are involved in mediating the damage induced by the SM and that iodine-related reduction in acute epidermal inflammation is associated with reduced iNOS expression. JF - Archives of toxicology AU - Nyska, A AU - Lomnitski, L AU - Maronpot, R AU - Moomaw, C AU - Brodsky, B AU - Sintov, A AU - Wormser, U AD - Laboratory of Experimental Pathology, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. nyska@niehs.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 768 EP - 774 VL - 74 IS - 12 SN - 0340-5761, 0340-5761 KW - Anti-Infective Agents, Local KW - 0 KW - Chemical Warfare Agents KW - Isoenzymes KW - Povidone-Iodine KW - 25655-41-8 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Mustard Gas KW - T8KEC9FH9P KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Enzyme Induction KW - Male KW - Immunoenzyme Techniques KW - Administration, Topical KW - Skin Diseases -- enzymology KW - Skin Diseases -- pathology KW - Skin Diseases -- prevention & control KW - Skin Diseases -- chemically induced KW - Chemical Warfare Agents -- toxicity KW - Povidone-Iodine -- pharmacology KW - Nitric Oxide Synthase -- biosynthesis KW - Povidone-Iodine -- administration & dosage KW - Anti-Infective Agents, Local -- pharmacology KW - Isoenzymes -- biosynthesis KW - Mustard Gas -- toxicity KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Anti-Infective Agents, Local -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77059211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=Effects+of+iodine+on+inducible+nitric+oxide+synthase+and+cyclooxygenase-2+expression+in+sulfur+mustard-induced+skin.&rft.au=Nyska%2C+A%3BLomnitski%2C+L%3BMaronpot%2C+R%3BMoomaw%2C+C%3BBrodsky%2C+B%3BSintov%2C+A%3BWormser%2C+U&rft.aulast=Nyska&rft.aufirst=A&rft.date=2001-02-01&rft.volume=74&rft.issue=12&rft.spage=768&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=03405761&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ewing sarcoma and sinonasal neuroectodermal tumors as second malignant tumors after retinoblastoma and other neoplasms. AN - 71016215; 11452937 AB - Excesses of various childhood cancers have been reported after retinoblastoma, including a trickle of Ewing sarcoma (ES) and perhaps histologically similar olfactory neuroblastoma, both of which are neural tumors. To update and advance this information, case reports were sought by an extensive review of the literature. The search was made through the use of PubMed, and the Web of Science (Citation Index Expanded), keying on primary references. Three sinonasal cancers diagnosed as ES were immunohistochemically stained for MIC-2 protein (positive in ES). Retinoblastoma occurred before ES in ten cases (seven bilateral). In four others, retinoblastoma (three bilateral) developed before sinonasal neural tumors (poorly differentiated). ES also occurred after 14 cancers other than retinoblastoma (five lymphomas, four leukemias, and one each of five miscellaneous cancers). The predominance of retinoblastoma prior to ES differs markedly from the low-frequency of retinoblastoma among childhood cancers in the general population. On the contrary, cancers other than retinoblastoma were proportionate to those in the general population. Previously, retinoblastoma followed by excesses of osteosarcoma and soft tissue sarcomas has been attributed to the action of the inherited RB-1 gene. The sinonasal tumors stained negative for MIC-2 protein. Heritable retinoblastoma may predispose to ES and perhaps to a subset of poorly differentiated neuroectodermal tumors in the sinonasal region that may be related to olfactory neuroblastoma. JF - Medical and pediatric oncology AU - Cope, J U AU - Tsokos, M AU - Miller, R W AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7362, USA. judy_cope@nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 290 EP - 294 VL - 36 IS - 2 SN - 0098-1532, 0098-1532 KW - Index Medicus KW - Age Factors KW - Genes, Retinoblastoma KW - Humans KW - Child KW - Adolescent KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Child, Preschool KW - Sarcoma, Ewing -- etiology KW - Retinoblastoma -- complications KW - Retinal Neoplasms -- complications KW - Neuroectodermal Tumors -- etiology KW - Neoplasms, Second Primary -- etiology KW - Nose Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71016215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology&rft.atitle=Ewing+sarcoma+and+sinonasal+neuroectodermal+tumors+as+second+malignant+tumors+after+retinoblastoma+and+other+neoplasms.&rft.au=Cope%2C+J+U%3BTsokos%2C+M%3BMiller%2C+R+W&rft.aulast=Cope&rft.aufirst=J&rft.date=2001-02-01&rft.volume=36&rft.issue=2&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology&rft.issn=00981532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. AN - 70821030; 11345515 AB - Dietary restriction (DR) increases the lifespan of rodents and increases their resistance to several different age-related diseases including cancer and diabetes. Beneficial effects of DR on brain plasticity and neuronal vulnerability to injury have recently been reported, but the underlying mechanisms are unknown. We report that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex, and striatum of rats maintained on a DR regimen compared to animals fed ad libitum (AL). Seizure-induced damage to hippocampal neurons was significantly reduced in rats maintained on DR, and this beneficial effect was attenuated by intraventricular administration of a BDNF-blocking antibody. These findings provide the first evidence that diet can effect expression of a neurotrophic factor, demonstrate that BDNF signaling plays a central role in the neuroprotective effect of DR, and proffer DR as an approach for reducing neuronal damage in neurodegenerative disorders. JF - Journal of molecular neuroscience : MN AU - Duan, W AU - Lee, J AU - Guo, Z AU - Mattson, M P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 1 EP - 12 VL - 16 IS - 1 SN - 0895-8696, 0895-8696 KW - Actins KW - 0 KW - Antibodies KW - Brain-Derived Neurotrophic Factor KW - Neuroprotective Agents KW - Neurotoxins KW - RNA, Messenger KW - Glutamic Acid KW - 3KX376GY7L KW - Nerve Growth Factor KW - 9061-61-4 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Kainic Acid -- pharmacology KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- metabolism KW - Hippocampus -- metabolism KW - Epilepsy -- metabolism KW - Epilepsy -- drug therapy KW - Glutamic Acid -- pharmacology KW - Hippocampus -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Neostriatum -- metabolism KW - Actins -- antagonists & inhibitors KW - Epilepsy -- chemically induced KW - RNA, Messenger -- metabolism KW - Antibodies -- pharmacology KW - Neostriatum -- drug effects KW - Hippocampus -- physiopathology KW - Nerve Growth Factor -- biosynthesis KW - Nerve Growth Factor -- genetics KW - Immunohistochemistry KW - Male KW - Neurotoxins -- metabolism KW - Neurons -- metabolism KW - Brain-Derived Neurotrophic Factor -- biosynthesis KW - Brain-Derived Neurotrophic Factor -- antagonists & inhibitors KW - Neurons -- drug effects KW - Food Deprivation -- physiology KW - Brain -- drug effects KW - Neuroprotective Agents -- metabolism KW - Brain -- metabolism KW - Cell Survival -- physiology KW - Brain-Derived Neurotrophic Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70821030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+neuroscience+%3A+MN&rft.atitle=Dietary+restriction+stimulates+BDNF+production+in+the+brain+and+thereby+protects+neurons+against+excitotoxic+injury.&rft.au=Duan%2C+W%3BLee%2C+J%3BGuo%2C+Z%3BMattson%2C+M+P&rft.aulast=Duan&rft.aufirst=W&rft.date=2001-02-01&rft.volume=16&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=08958696&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacotherapy of ascariasis. AN - 70818196; 11336582 AB - Ascaris lumbricoides, the most frequent human intestinal nematode, is the causative agent of ascariasis, with an estimated worldwide prevalence of over one billion people, especially in moist tropical and subtropical regions, but also in cooler climates. Although characterised with low morbidity and mortality rates, the global prevalence of ascariasis still results in approximately 20,000 deaths annually, primarily as a consequence of intestinal obstruction. In humans, transmission usually occurs by hand-to-mouth route by way of contaminated agricultural products and food, or from dirty hands. Three phases of ascariasis may be present, namely, the pulmonary, intestinal and the complications stage. Although generally asymptomatic, heavy infestation may cause serious pulmonary disease, or partial or complete obstruction of biliary or intestinal tracts. Anthelminthic chemotherapy is required to eradicate the parasites and prevent potentially serious complications. Mebendazole, albendazole and pyrantel pamoate are the most widely used agents to treat ascariasis. Preventive chemotherapy delivered to communities in endemic regions may serve as an affordable and cost-effective strategy to reduce the prevalence and morbidity in endemic regions. Under unusual circumstances, Ascaris suum, the cause of helminthic infection in pigs, may also cause disease in humans. JF - Expert opinion on pharmacotherapy AU - St Georgiev, V AD - National Institute of Allergy and Infectious Diseases, NIH 6700-B Rockledge Drive, Room 2102, Bethesda, MD 20892, USA. vg8q@nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 223 EP - 239 VL - 2 IS - 2 SN - 1465-6566, 1465-6566 KW - Antiparasitic Agents KW - 0 KW - Drugs, Chinese Herbal KW - Index Medicus KW - Swine KW - Drug Therapy, Combination KW - Animals KW - Randomized Controlled Trials as Topic KW - Drugs, Chinese Herbal -- therapeutic use KW - Humans KW - Swine Diseases -- parasitology KW - Treatment Outcome KW - Swine Diseases -- drug therapy KW - Child KW - Ascaris suum -- drug effects KW - Male KW - Female KW - Pregnancy KW - Infectious Disease Transmission, Vertical KW - Ascariasis -- drug therapy KW - Antiparasitic Agents -- therapeutic use KW - Pregnancy Complications, Parasitic -- drug therapy KW - Antiparasitic Agents -- adverse effects KW - Ascariasis -- transmission KW - Ascariasis -- veterinary KW - Ascaris lumbricoides -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70818196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+pharmacotherapy&rft.atitle=Pharmacotherapy+of+ascariasis.&rft.au=St+Georgiev%2C+V&rft.aulast=St+Georgiev&rft.aufirst=V&rft.date=2001-02-01&rft.volume=2&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+pharmacotherapy&rft.issn=14656566&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-07 N1 - Date created - 2001-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targets for molecular intervention in multistep pulmonary carcinogenesis. AN - 70792148; 11338019 AB - Lung cancers are a leading cause of mortality worldwide, and most of these neoplasms are directly attributable to tobacco abuse. Recent studies have begun to elucidate molecular mechanisms of multistep aero-digestive tract carcinogenesis, revealing novel targets for intervention in lung cancers and their precursor lesions. This review summarizes the molecular biology of lung cancers in relation to the prognosis and treatment of patients with these neoplasms. JF - World journal of surgery AU - Schrump, D S AU - Nguyen, D M AD - Thoracic Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B-07, 10 Center Drive, Bethesda, Maryland 20892-1502, USA. david_schrump@nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 174 EP - 183 VL - 25 IS - 2 SN - 0364-2313, 0364-2313 KW - Platelet-Derived Growth Factor KW - 0 KW - Retinoblastoma Protein KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Platelet-Derived Growth Factor -- metabolism KW - Proto-Oncogenes -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Humans KW - DNA Repair -- physiology KW - Phosphorylation KW - Genes, p53 -- genetics KW - Genes, Tumor Suppressor -- physiology KW - Retinoblastoma Protein -- genetics KW - Cell Transformation, Neoplastic KW - Cell Division KW - G1 Phase -- physiology KW - Lung Neoplasms -- therapy KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70792148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=World+journal+of+surgery&rft.atitle=Targets+for+molecular+intervention+in+multistep+pulmonary+carcinogenesis.&rft.au=Schrump%2C+D+S%3BNguyen%2C+D+M&rft.aulast=Schrump&rft.aufirst=D&rft.date=2001-02-01&rft.volume=25&rft.issue=2&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=World+journal+of+surgery&rft.issn=03642313&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fetal alcohol syndrome. AN - 70649850; 11157101 JF - Pediatrics in review AU - Thackray, H AU - Tifft, C AD - Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 47 EP - 55 VL - 22 IS - 2 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Lactation -- drug effects KW - Ethanol -- adverse effects KW - Breast Feeding -- adverse effects KW - Diagnosis, Differential KW - Humans KW - Infant, Newborn KW - Abnormalities, Multiple -- psychology KW - Abnormalities, Multiple -- diagnosis KW - Alcoholism -- complications KW - Female KW - Abnormalities, Multiple -- etiology KW - Pregnancy KW - Fetal Alcohol Spectrum Disorders -- psychology KW - Fetal Alcohol Spectrum Disorders -- etiology KW - Fetal Alcohol Spectrum Disorders -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70649850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics+in+review&rft.atitle=Fetal+alcohol+syndrome.&rft.au=Thackray%2C+H%3BTifft%2C+C&rft.aulast=Thackray&rft.aufirst=H&rft.date=2001-02-01&rft.volume=22&rft.issue=2&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Pediatrics+in+review&rft.issn=1526-3347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-18 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network. AN - 70649440; 11228500 AB - The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised. JF - American journal of obstetrics and gynecology AU - Newman, R B AU - Goldenberg, R L AU - Moawad, A H AU - Iams, J D AU - Meis, P J AU - Das, A AU - Miodovnik, M AU - Caritis, S N AU - Thurnau, G R AU - Dombrowski, M P AU - Roberts, J AU - National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network AD - National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, USA. ; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 438 EP - 446 VL - 184 IS - 3 SN - 0002-9378, 0002-9378 KW - Abridged Index Medicus KW - Index Medicus KW - Parity KW - Regression Analysis KW - Obstetric Labor, Premature -- etiology KW - Educational Status KW - Humans KW - Alcohol Drinking KW - Pregnancy KW - Smoking KW - Prospective Studies KW - Logistic Models KW - Adult KW - Cohort Studies KW - Surveys and Questionnaires KW - Substance-Related Disorders KW - Adolescent KW - Female KW - Fetal Membranes, Premature Rupture -- etiology KW - Fatigue -- complications KW - Work UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70649440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+obstetrics+and+gynecology&rft.atitle=Occupational+fatigue+and+preterm+premature+rupture+of+membranes.+National+Institute+of+Child+Health+and+Human+Development+Maternal-Fetal+Medicine%2C+Units+Network.&rft.au=Newman%2C+R+B%3BGoldenberg%2C+R+L%3BMoawad%2C+A+H%3BIams%2C+J+D%3BMeis%2C+P+J%3BDas%2C+A%3BMiodovnik%2C+M%3BCaritis%2C+S+N%3BThurnau%2C+G+R%3BDombrowski%2C+M+P%3BRoberts%2C+J%3BNational+Institute+of+Child+Health+and+Human+Development+Maternal-Fetal+Medicine+Units+Network&rft.aulast=Newman&rft.aufirst=R&rft.date=2001-02-01&rft.volume=184&rft.issue=3&rft.spage=438&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of mutation spectra analysis software. AN - 70648527; 11180592 AB - The study and comparison of mutation(al) spectra is an important problem in molecular biology, because these spectra often reflect on important features of mutations and their fixation. Such features include the interaction of DNA with various mutagens, the function of repair/replication enzymes, and properties of target proteins. It is known that mutability varies significantly along nucleotide sequences, such that mutations often concentrate at certain positions, called "hotspots," in a sequence. In this paper, we discuss in detail two approaches for mutation spectra analysis: the comparison of mutation spectra with a HG-PUBL program, (FTP: sunsite.unc.edu/pub/academic/biology/dna-mutations/hyperg) and hotspot prediction with the CLUSTERM program (www.itba.mi.cnr.it/webmutation; ftp.bionet.nsc.ru/pub/biology/dbms/clusterm.zip). Several other approaches for mutational spectra analysis, such as the analysis of a target protein structure, hotspot context revealing, multiple spectra comparisons, as well as a number of mutation databases are briefly described. Mutation spectra in the lacI gene of E. coli and the human p53 gene are used for illustration of various difficulties of such analysis. Copyright 2001 Wiley-Liss, Inc. JF - Human mutation AU - Rogozin, I AU - Kondrashov, F AU - Glazko, G AD - Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia. rogozin@ncbi.nlm.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 83 EP - 102 VL - 17 IS - 2 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Tumor Suppressor Protein p53 -- genetics KW - Sequence Homology, Amino Acid KW - Software KW - DNA Mutational Analysis -- methods KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70648527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+mutation&rft.atitle=Use+of+mutation+spectra+analysis+software.&rft.au=Rogozin%2C+I%3BKondrashov%2C+F%3BGlazko%2C+G&rft.aulast=Rogozin&rft.aufirst=I&rft.date=2001-02-01&rft.volume=17&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-02 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Wild-type p53 marginally induces endogenous MDR-1 mRNA without causing a measurable drug resistance in human cancer cells. AN - 70647770; 11172607 AB - The notion that wt p53 downregulates MDR-1 links p53 mutations to multidrug resistant phenotype. Alternatively, it has been envisioned that wt p53 protects cells against DNA damaging drugs by inducing MDR-1. Opposing conclusions on the relationship between MDR-1 and p53 have been predominantly based on the effects of p53 on MDR-1 promoter-constructs. We found that introduction of wt p53 slightly induced MDR-1 mRNA in three cell lines having endogenous mt p53. Wt p53-mediated induction of endogenous MDR-1 may represent a rudiment of cellular protection against toxic compounds earlier in evolution. Marked induction of p21WAF1/CIP1 (p21) mRNA was observed in all cell lines; and lower levels of wt p53 were required to induce p21 than MDR-1. Pgp was undetectable and wt p53 did not increase resistance to an MDR-1 substrate, suggesting the changes in MDR-1 mRNA may be functionally insignificant. Unlike endogenous MDR-1, the expression of an MDR-1 promoter (-434/+147 fragment) - luciferase construct was unchanged or even inhibited by wt p53 that may be secondary to wt p53-mediated cytotoxicity. Thus, partial promoter constructs may not accurately represent endogenous MDR-1. JF - International journal of oncology AU - Nicoletti, M I AU - Myers, T G AU - Fojo, T AU - Blagosklonny, M V AD - Medicine Branch and Developmental Therapeutics Program, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 375 EP - 381 VL - 18 IS - 2 SN - 1019-6439, 1019-6439 KW - Antibiotics, Antineoplastic KW - 0 KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Dactinomycin KW - 1CC1JFE158 KW - rho GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Promoter Regions, Genetic -- physiology KW - Dactinomycin -- pharmacology KW - Adenoviridae KW - Tumor Cells, Cultured -- metabolism KW - RNA, Messenger -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Antibiotics, Antineoplastic -- pharmacology KW - Humans KW - RNA, Messenger -- drug effects KW - Drug Resistance, Neoplasm KW - Lac Operon KW - rho GTP-Binding Proteins -- drug effects KW - rho GTP-Binding Proteins -- metabolism KW - Kidney Neoplasms -- drug therapy KW - Genes, MDR -- physiology KW - Kidney Neoplasms -- metabolism KW - Genes, MDR -- drug effects KW - Tumor Suppressor Protein p53 -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70647770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Wild-type+p53+marginally+induces+endogenous+MDR-1+mRNA+without+causing+a+measurable+drug+resistance+in+human+cancer+cells.&rft.au=Nicoletti%2C+M+I%3BMyers%2C+T+G%3BFojo%2C+T%3BBlagosklonny%2C+M+V&rft.aulast=Nicoletti&rft.aufirst=M&rft.date=2001-02-01&rft.volume=18&rft.issue=2&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol esters modulate the Ras exchange factor RasGRP3. AN - 70646978; 11221888 AB - RasGRP represents the prototype of a new class of guanine nucleotide exchange factors that activate small GTPases. The guanyl nucleotide-releasing protein (GRP) family members contain catalytic domains related to CDC25, the Ras exchange factor of Saccharomyces cerevisiae. They also contain a motif resembling a pair of calcium-binding EF-hands and a C1 domain similar to the diacylglycerol interaction domain of protein kinase C. The sequence of KIAA0846, identified in a human brain cDNA library, encodes a member of the GRP family that we refer to as RasGRP3. We show here that RasGRP3 bound phorbol esters with high affinity. This binding depended on anionic phospholipids, which is characteristic of phorbol ester binding to C1 domain proteins. In addition, phorbol esters also caused activation of the RasGRP3 exchange activity in intact cells, as determined by an increase in RasGTP and phosphorylation of the extracellular-regulated kinases. Finally, both phorbol 12-myristate 13-acetate and the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol induced redistribution of RasGRP3 to the plasma membrane and/or perinuclear area in HEK-293 cells, as demonstrated using a green fluorescent fusion protein. We conclude that RasGRP3 serves as a PKC-independent pathway to link the tumor-promoting phorbol esters with activation of Ras GTPases. JF - Cancer research AU - Lorenzo, P S AU - Kung, J W AU - Bottorff, D A AU - Garfield, S H AU - Stone, J C AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 943 EP - 949 VL - 61 IS - 3 SN - 0008-5472, 0008-5472 KW - Caenorhabditis elegans Proteins KW - 0 KW - Carcinogens KW - Carrier Proteins KW - Guanine Nucleotide Exchange Factors KW - Phorbol Esters KW - RASGRP3 protein, human KW - Receptors, Drug KW - phorbol ester binding protein KW - phorbol ester receptor KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Monomeric GTP-Binding Proteins -- metabolism KW - Amino Acid Sequence KW - Chromosome Mapping KW - Rats KW - Protein Kinase C -- metabolism KW - Tetradecanoylphorbol Acetate -- metabolism KW - Receptors, Drug -- metabolism KW - Kinetics KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Subcellular Fractions -- metabolism KW - Cell Membrane -- metabolism KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Cell Line KW - Phorbol Esters -- pharmacology KW - Carcinogens -- pharmacology KW - Phorbol Esters -- metabolism KW - Carcinogens -- metabolism KW - Guanine Nucleotide Exchange Factors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70646978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Phorbol+esters+modulate+the+Ras+exchange+factor+RasGRP3.&rft.au=Lorenzo%2C+P+S%3BKung%2C+J+W%3BBottorff%2C+D+A%3BGarfield%2C+S+H%3BStone%2C+J+C%3BBlumberg%2C+P+M&rft.aulast=Lorenzo&rft.aufirst=P&rft.date=2001-02-01&rft.volume=61&rft.issue=3&rft.spage=943&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833. AN - 70646247; 11157037 AB - PSC 833 (valspodar) is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance. We conducted a phase I study of a 7-day oral administration of PSC 833 in combination with paclitaxel, administered as a 96-hour continuous infusion. Fifty patients with advanced cancer were enrolled onto the trial. PSC 833 was administered orally for 7 days, beginning 72 hours before the start of the paclitaxel infusion. Paclitaxel dose reductions were planned because of the pharmacokinetic interactions known to occur with PSC 833. In combination with PSC 833, maximum-tolerated doses were defined as paclitaxel 13.1 mg/m(2)/d continuous intravenous infusion (CIVI) for 4 days without filgrastim, and paclitaxel 17.5 mg/m(2)/d CIVI for 4 days with filgrastim support. Dose-limiting toxicity for the combination was neutropenia. Statistical analysis of cohorts revealed similar mean steady-state concentrations (C(pss)) and areas under the concentration-versus-time curve (AUCs) when patients received paclitaxel doses of 13.1 or 17.5 mg/m(2)/d for 4 days with PSC 833, as when they received a paclitaxel dose of 35 mg/m(2)/d for 4 days without PSC 833. However, the effect of PSC 833 on paclitaxel pharmacokinetics varied greatly among individual patients, although a surrogate assay using CD56+ cells suggested inhibition of Pgp was complete or nearly complete at low concentrations of PSC 833. Responses occurred in three of four patients with non-small-cell lung cancer, and clinical benefit occurred in five of 10 patients with ovarian carcinoma. PSC 833 in combination with paclitaxel can be administered safely to patients provided the paclitaxel dose is reduced to compensate for the pharmacokinetic interaction. Surrogate studies with CD56+ cells indicate that the maximum-tolerated dose for PSC 833 gives serum levels much higher than those required to block Pgp. The variability in paclitaxel pharmacokinetics, despite complete inhibition of Pgp in the surrogate assay, suggests that other mechanisms, most likely related to P450, contribute to the pharmacokinetic interaction. Future development of combinations such as this should include strategies to predict pharmacokinetics of the chemotherapeutic agent. This in turn will facilitate dosing to achieve comparable CPss and AUCs. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Chico, I AU - Kang, M H AU - Bergan, R AU - Abraham, J AU - Bakke, S AU - Meadows, B AU - Rutt, A AU - Robey, R AU - Choyke, P AU - Merino, M AU - Goldspiel, B AU - Smith, T AU - Steinberg, S AU - Figg, W D AU - Fojo, T AU - Bates, S AD - Medicine Branch and Department of Pathology, Division of Clinical Sciences, National Cancer Institute, National Institutesof Health, Bethesda, MD 20892, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 832 EP - 842 VL - 19 IS - 3 SN - 0732-183X, 0732-183X KW - Antigens, CD56 KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Cyclosporins KW - Fluorescent Dyes KW - P-Glycoprotein KW - Rhodamines KW - Paclitaxel KW - P88XT4IS4D KW - valspodar KW - Q7ZP55KF3X KW - Index Medicus KW - Cyclosporins -- adverse effects KW - Paclitaxel -- administration & dosage KW - Antigens, CD56 -- biosynthesis KW - Humans KW - Paclitaxel -- pharmacokinetics KW - Aged KW - P-Glycoprotein -- antagonists & inhibitors KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Aged, 80 and over KW - Adult KW - Fluorescent Dyes -- pharmacokinetics KW - T-Lymphocytes -- drug effects KW - Adolescent KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - T-Lymphocytes -- immunology KW - Male KW - Rhodamines -- pharmacokinetics KW - Administration, Oral KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Cyclosporins -- administration & dosage KW - T-Lymphocytes -- metabolism KW - Paclitaxel -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Middle Aged KW - Female KW - Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70646247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+study+of+infusional+paclitaxel+in+combination+with+the+P-glycoprotein+antagonist+PSC+833.&rft.au=Chico%2C+I%3BKang%2C+M+H%3BBergan%2C+R%3BAbraham%2C+J%3BBakke%2C+S%3BMeadows%2C+B%3BRutt%2C+A%3BRobey%2C+R%3BChoyke%2C+P%3BMerino%2C+M%3BGoldspiel%2C+B%3BSmith%2C+T%3BSteinberg%2C+S%3BFigg%2C+W+D%3BFojo%2C+T%3BBates%2C+S&rft.aulast=Chico&rft.aufirst=I&rft.date=2001-02-01&rft.volume=19&rft.issue=3&rft.spage=832&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL. AN - 70645021; 11160212 AB - Previously, we observed that high-avidity CTL are much more effective in vivo than low-avidity CTL in elimination of infected cells, but the mechanisms behind their superior activity remained unclear. In this study, we identify two complementary mechanisms: 1) high-avidity CTL lyse infected cells earlier in the course of a viral infection by recognizing lower Ag densities than those distinguished by low-avidity CTL and 2) they initiate lysis of target cells more rapidly at any given Ag density. Alternative mechanisms were excluded, including: 1) the possibility that low-avidity CTL might control virus given more time (virus levels remained as high at 6 days following transfer as at 3 days) and 2) that differences in efficacy might be correlated with homing ability. Furthermore, adoptive transfer of high- and low-avidity CTL into SCID mice demonstrated that transfer of a 10-fold greater amount of low-avidity CTL could only partially compensate for their decreased ability to eliminate infected cells. Thus, we conclude that high-avidity CTL exploit two complementary mechanisms that combine to prevent the spread of virus within the animal: earlier recognition of infected cells when little viral protein has been made and more rapid lysis of infected cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Derby, M AU - Alexander-Miller, M AU - Tse, R AU - Berzofsky, J AD - Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 1690 EP - 1697 VL - 166 IS - 3 SN - 0022-1767, 0022-1767 KW - HIV Antigens KW - 0 KW - HIV Envelope Protein gp160 KW - HIV-1 gp160 (315-329) KW - Peptide Fragments KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Animals KW - Vaccinia virus -- immunology KW - Ovarian Diseases -- virology KW - Cell Movement -- immunology KW - Vaccinia -- virology KW - Mice, Inbred BALB C KW - Tumor Cells, Cultured KW - HIV Envelope Protein gp160 -- genetics KW - HIV Antigens -- metabolism KW - Peptide Fragments -- metabolism KW - Vaccinia virus -- genetics KW - HIV Envelope Protein gp160 -- immunology KW - Antigen Presentation KW - Vaccinia -- immunology KW - Peptide Fragments -- genetics KW - HIV Envelope Protein gp160 -- metabolism KW - Ovarian Diseases -- immunology KW - Mice KW - HIV Antigens -- immunology KW - Peptide Fragments -- immunology KW - Mice, Inbred DBA KW - Viral Load KW - Adoptive Transfer KW - Kinetics KW - Mice, SCID KW - HIV Antigens -- genetics KW - Female KW - Cell Line KW - T-Lymphocyte Subsets -- metabolism KW - Cytotoxicity, Immunologic KW - Cytotoxicity Tests, Immunologic -- methods KW - T-Lymphocytes, Cytotoxic -- transplantation KW - T-Lymphocyte Subsets -- transplantation KW - T-Lymphocyte Subsets -- immunology KW - T-Lymphocyte Subsets -- virology KW - T-Lymphocytes, Cytotoxic -- immunology KW - T-Lymphocytes, Cytotoxic -- virology KW - T-Lymphocytes, Cytotoxic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70645021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=High-avidity+CTL+exploit+two+complementary+mechanisms+to+provide+better+protection+against+viral+infection+than+low-avidity+CTL.&rft.au=Derby%2C+M%3BAlexander-Miller%2C+M%3BTse%2C+R%3BBerzofsky%2C+J&rft.aulast=Derby&rft.aufirst=M&rft.date=2001-02-01&rft.volume=166&rft.issue=3&rft.spage=1690&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amino-terminal modification and tyrosine phosphorylation of [corrected] carboxy-terminal fragments of the amyloid precursor protein in Alzheimer's disease and Down's syndrome brain. AN - 70644159; 11162251 AB - The carboxy-terminal fragments (CTFs) of the amyloid precursor protein (APP) are considered beta-amyloid (Abeta) precursors as well as molecular species possibly amyloidogenic and neurotoxic by [corrected] in vitro or in animal models. The CTF's role in the pathogenesis of Alzheimer's disease (AD) is however relatively unexplored in human brain. In this study, we analyzed brain extracted CTFs in subjects with AD, non-AD control, and Down's syndrome (DS) cases. Our data indicate that: (i) In fetal DS subjects CTFs levels are increased in comparison to age-matched control, suggesting that the enhanced CTFs formation is important for the early occurrence of plaques deposition in DS. No significant difference in CTFs level [corrected] between AD and age-matched control cases. (ii) CTFs modified at their N-terminus are the direct precursors of similarly N-terminally modified Abeta peptides, which constitute the most abundant species in AD and DS plaques. This observation suggests that N-truncated Abeta peptides are formed directly at beta-secretase level and not through a progressive proteolysis of full-length Abeta1-40/42. (iii) Among the differently cleaved CTFs, only the 22- and 12.5-kDa CTF polypeptides are tyrosine phosphorylated in both AD and control brain while the full-length APP and the CTFs migrating below the 12.5-kDa marker are not phosphorylated, suggesting that APP and CTFs may be involved in different pathways depending on their length and sequences. This study provides evidence that CTFs constitute in human brain a molecular species directly involved in AD pathogenesis and in the development of the AD-like pathology in DS subjects. Copyright 2001 Academic Press. JF - Neurobiology of disease AU - Russo, C AU - Salis, S AU - Dolcini, V AU - Venezia, V AU - Song, X H AU - Teller, J K AU - Schettini, G AD - Section of Pharmacology and Neuroscience, National Cancer Institute, Genova, Italy. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 173 EP - 180 VL - 8 IS - 1 SN - 0969-9961, 0969-9961 KW - Amyloid beta-Protein Precursor KW - 0 KW - Antibodies KW - Peptide Fragments KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Pyrrolidonecarboxylic Acid KW - SZB83O1W42 KW - Index Medicus KW - Antibodies -- immunology KW - Blotting, Western KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Tyrosine -- metabolism KW - Adolescent KW - Pyrrolidonecarboxylic Acid -- metabolism KW - Male KW - Female KW - Densitometry KW - Peptide Fragments -- metabolism KW - Phosphotyrosine -- chemistry KW - Amyloid beta-Protein Precursor -- immunology KW - Down Syndrome -- metabolism KW - Amyloid beta-Protein Precursor -- metabolism KW - Alzheimer Disease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70644159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=Amino-terminal+modification+and+tyrosine+phosphorylation+of+%5Bcorrected%5D+carboxy-terminal+fragments+of+the+amyloid+precursor+protein+in+Alzheimer%27s+disease+and+Down%27s+syndrome+brain.&rft.au=Russo%2C+C%3BSalis%2C+S%3BDolcini%2C+V%3BVenezia%2C+V%3BSong%2C+X+H%3BTeller%2C+J+K%3BSchettini%2C+G&rft.aulast=Russo&rft.aufirst=C&rft.date=2001-02-01&rft.volume=8&rft.issue=1&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=09699961&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Neurobiol Dis 2001 Jun;8(3):540 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mercury vapor and female reproductive toxicity. AN - 70644076; 11158722 AB - Epidemiological studies finding menstrual cycle abnormalities among women occupationally exposed to Hg degrees prompted us to investigate the mechanisms of reproductive toxicity of Hg degrees in the female rat. Nose-only Hg degrees vapor inhalation exposures were conducted on regularly cycling rats 80-90 days of age in dose-response and acute time-course studies, which have previously proven useful as a model to identify ovarian toxicants. Vaginal smears were evaluated daily and serum hormone levels were correlated with cycle and with ovarian morphology at necropsy. Exposure concentration-related effects of Hg degrees were evaluated by exposing rats to 0, 1, 2, or 4 mg/m3 Hg degrees vapor 2 h/day for 11 consecutive days. Tissue Hg levels correlated with exposure concentration and duration. Exposure of rats to 4 mg/m3 (but not 1 or 2 mg/m3) Hg vapor for 11 days resulted in significant decreases in body weights relative to controls. Estrous cycles were slightly prolonged in the 2 and 4 mg/m3 dose groups, and serum estradiol and progesterone levels were significantly different in the 4 mg/m3 group compared to controls. The alterations in cycle and hormones at the 4 mg/m3 exposure concentration were attributed to body weight loss and generalized toxicity. In the time-course study, rats were exposed to 2 mg/m3 Hg degrees or air beginning in metestrus and evaluated daily for 8 days. A lengthening of the cycle was detected and morphological changes were observed in the corpora lutea (CL) after exposure for 6 days. To determine if changes in the CL and cyclicity correlated with a functional defect, rats were exposed to Hg degrees vapor and evaluated for pregnancy outcome. There were no significant effects on pregnancy rate or numbers of implantation sites when rats were exposed to 1 or 2 mg/m3 Hg degrees for 8 days prior to breeding, or when exposed for 8 days after breeding. These studies indicate that exposure to Hg degrees vapor altered estrous cyclicity, but had no significant effect on ovulation, implantation, or maintenance of first pregnancy during exposure of short duration in female rats. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Davis, B J AU - Price, H C AU - O'Connor, R W AU - Fernando, R AU - Rowland, A S AU - Morgan, D L AD - National Institute of Environmental Sciences, MD A2-01, Research Triangle Park, North Carolina 27709, USA. davis1@niehs.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 291 EP - 296 VL - 59 IS - 2 SN - 1096-6080, 1096-6080 KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Ovary -- drug effects KW - Longevity -- drug effects KW - Kidney -- drug effects KW - Volatilization KW - Brain -- metabolism KW - Pregnancy KW - Rats KW - Ovary -- metabolism KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Estradiol -- blood KW - Body Weight -- drug effects KW - Administration, Inhalation KW - Time Factors KW - Progesterone -- blood KW - Male KW - Female KW - Organ Size -- drug effects KW - Fertility -- drug effects KW - Reproduction -- drug effects KW - Mercury -- administration & dosage KW - Mercury -- pharmacokinetics KW - Mercury -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70644076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Mercury+vapor+and+female+reproductive+toxicity.&rft.au=Davis%2C+B+J%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BFernando%2C+R%3BRowland%2C+A+S%3BMorgan%2C+D+L&rft.aulast=Davis&rft.aufirst=B&rft.date=2001-02-01&rft.volume=59&rft.issue=2&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells. AN - 70641429; 11221885 AB - Transcriptional repression of the transforming growth factor (TGF)-1P type II receptor (TPRII) gene appears to be a major mechanism to inactivate TGF-beta responsiveness in many human cancers. Because histone acetylation/deacetylation plays a role in transcriptional regulation, we have examined the effect of MS-275, a synthetic inhibitor of histone deacetylase, in human breast cancer cell lines. MS-275 showed antiproliferative activity against all human breast cancer cell lines examined and induced TbetaRII mRNA, but not TGF-beta type I receptor mRNA. MS-275 caused an accumulation of acetylated histones H3 and H4 in total cellular chromatin. An increase in the accumulation of acetylated histones H3 and H4 was detected in the TbetaRII promoter after treatment with MS-275. However, the level of histone acetylation did not change in chromatin associated with the TGF-beta type I receptor gene. MS-275 treatment enhanced TGF-beta1-induced plasminogen activator inhibitor 1 expression. Thus, antitumor activity of MS-275 may be mediated in part through the induction of TbetaRII expression and consequent potentiation of TGF-beta signaling. JF - Cancer research AU - Lee, B I AU - Park, S H AU - Kim, J W AU - Sausville, E A AU - Kim, H T AU - Nakanishi, O AU - Trepel, J B AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 931 EP - 934 VL - 61 IS - 3 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Benzamides KW - Chromatin KW - Enzyme Inhibitors KW - Growth Inhibitors KW - Histone Deacetylase Inhibitors KW - Histones KW - Plasminogen Activator Inhibitor 1 KW - Pyridines KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - entinostat KW - 1ZNY4FKK9H KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Gene Expression -- drug effects KW - Acetylation -- drug effects KW - Chromatin -- metabolism KW - Plasminogen Activator Inhibitor 1 -- biosynthesis KW - Humans KW - Cell Division -- drug effects KW - Histones -- drug effects KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Transforming Growth Factor beta -- physiology KW - Tumor Cells, Cultured KW - Histones -- metabolism KW - Signal Transduction -- drug effects KW - Growth Inhibitors -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Breast Neoplasms -- genetics KW - Receptors, Transforming Growth Factor beta -- genetics KW - Breast Neoplasms -- pathology KW - Benzamides -- pharmacology KW - Breast Neoplasms -- metabolism KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Pyridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70641429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=MS-275%2C+a+histone+deacetylase+inhibitor%2C+selectively+induces+transforming+growth+factor+beta+type+II+receptor+expression+in+human+breast+cancer+cells.&rft.au=Lee%2C+B+I%3BPark%2C+S+H%3BKim%2C+J+W%3BSausville%2C+E+A%3BKim%2C+H+T%3BNakanishi%2C+O%3BTrepel%2C+J+B%3BKim%2C+S+J&rft.aulast=Lee&rft.aufirst=B&rft.date=2001-02-01&rft.volume=61&rft.issue=3&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Closeout of four phase II Vanguard trials and patient rollover into a large international phase III HIV clinical endpoint trial. AN - 70640745; 11165422 AB - Large phase III clinical trials typically require many years of planning and preparation. During this time, proposed study methods and overall trial feasibility can be assessed in smaller pilot studies. However, the patients enrolled in these pilot studies are not routinely included in the larger study. In preparation for a multinational randomized clinical end point trial of interleukin-2 in HIV-infected patients, four phase II "Vanguard" studies were initiated. These Vanguard trials served to increase safety and surrogate marker data in diverse patient cohorts, increase clinical experience with the study medication, and identify the optimal dose of medication for the phase III trial. These trials also served to assess patient recruitment potential and to develop international clinical trial coordination experience. The Vanguard trials were designed to allow continued follow-up of their patients as participants of the phase III trial once the feasibility of the phase III trial was confirmed. The purpose of this paper is to describe the steps taken in the closeout of these four phase II trials while reconsenting these patients to the phase III trial. Specifically, the reconsent process, the data collection transition plan, and the steps taken to minimize bias due to differential reconsent according to the assigned treatment arm in the phase II trial are described. The procedures employed are relevant to the reconsent of patients for long-term follow-up at the completion of clinical trials. Control Clin Trials 2001;22:42-48 JF - Controlled clinical trials AU - Tavel, J A AU - Fosdick, L AU - ESPRIT Vanguard Group. ESPRIT Executive Committee AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1880, USA. jtavel@nih.gov ; ESPRIT Vanguard Group. ESPRIT Executive Committee Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 42 EP - 48 VL - 22 IS - 1 SN - 0197-2456, 0197-2456 KW - Anti-HIV Agents KW - 0 KW - Interleukin-2 KW - Index Medicus KW - Drug Therapy, Combination KW - Data Collection -- statistics & numerical data KW - Drug Administration Schedule KW - Survival Rate KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Pilot Projects KW - Follow-Up Studies KW - Patient Selection KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - HIV Infections -- immunology KW - Clinical Trials, Phase II as Topic -- statistics & numerical data KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects KW - Anti-HIV Agents -- administration & dosage KW - HIV Infections -- mortality KW - Outcome and Process Assessment (Health Care) -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70640745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Controlled+clinical+trials&rft.atitle=Closeout+of+four+phase+II+Vanguard+trials+and+patient+rollover+into+a+large+international+phase+III+HIV+clinical+endpoint+trial.&rft.au=Tavel%2C+J+A%3BFosdick%2C+L%3BESPRIT+Vanguard+Group.+ESPRIT+Executive+Committee&rft.aulast=Tavel&rft.aufirst=J&rft.date=2001-02-01&rft.volume=22&rft.issue=1&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Controlled+clinical+trials&rft.issn=01972456&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repaglinide-induced factitious hypoglycemia. AN - 70640616; 11157993 AB - We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution. JF - The Journal of clinical endocrinology and metabolism AU - Hirshberg, B AU - Skarulis, M C AU - Pucino, F AU - Csako, G AU - Brennan, R AU - Gorden, P AD - Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Diseases, W. G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 475 EP - 477 VL - 86 IS - 2 SN - 0021-972X, 0021-972X KW - Blood Glucose KW - 0 KW - Carbamates KW - Hypoglycemic Agents KW - Insulin KW - Piperidines KW - repaglinide KW - 668Z8C33LU KW - Abridged Index Medicus KW - Index Medicus KW - Diagnosis, Differential KW - Blood Glucose -- metabolism KW - Mental Disorders KW - Insulin -- blood KW - Humans KW - Insulin -- secretion KW - Fasting KW - Adolescent KW - Male KW - Piperidines -- poisoning KW - Carbamates -- poisoning KW - Poisoning -- diagnosis KW - Hypoglycemic Agents -- poisoning KW - Hypoglycemia -- chemically induced KW - Poisoning -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70640616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Repaglinide-induced+factitious+hypoglycemia.&rft.au=Hirshberg%2C+B%3BSkarulis%2C+M+C%3BPucino%2C+F%3BCsako%2C+G%3BBrennan%2C+R%3BGorden%2C+P&rft.aulast=Hirshberg&rft.aufirst=B&rft.date=2001-02-01&rft.volume=86&rft.issue=2&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: J Clin Endocrinol Metab. 2000 Dec;85(12):4592-5 [11134113] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of control of Listeria by nitric oxide redox chemistry from murine macrophages and NO donors: insights into listeriocidal activity of oxidative and nitrosative stress. AN - 70637859; 11165873 AB - The physiological function of nitric oxide (NO) in the defense against pathogens is multifaceted. The exact chemistry by which NO combats intracellular pathogens such as Listeria monocytogenes is yet unresolved. We examined the effects of NO exposure, either delivered by NO donors or generated in situ within ANA-1 murine macrophages, on L. monocytogenes growth. Production of NO by the two NONOate compounds PAPA/NO (NH2(C3H6)(N[N(O)NO]C3H7) and DEA/NO (Na(C2H5)2N[N(O)NO]) resulted in L. monocytogenes cytostasis with minimal cytotoxicity. Reactive oxygen species generated from xanthine oxidase/hypoxanthine were neither bactericidal nor cytostatic and did not alter the action of NO. L. monocytogenes growth was also suppressed upon internalization into ANA-1 murine macrophages primed with interferon-gamma (INF-gamma) + tumor necrosis factor-alpha (TNF-alpha or INF-gamma + lipid polysaccharide (LPS). Growth suppression correlated with nitrite formation and nitrosation of 2,3-diaminonaphthalene elicited by stimulated murine macrophages. This nitrosative chemistry was not dependent upon nor mediated by interaction with reactive oxygen species (ROS), but resulted solely from NO and intermediates related to nitrosative stress. The role of nitrosation in controlling L. monocytogenes was further examined by monitoring the effects of exposure to NO on an important virulence factor, Listeriolysin O, which was inhibited under nitrosative conditions. These results suggest that nitrosative stress mediated by macrophages is an important component of the immunological arsenal in controlling L. monocytogenes infections. JF - Free radical biology & medicine AU - Ogawa, R AU - Pacelli, R AU - Espey, M G AU - Miranda, K M AU - Friedman, N AU - Kim, S M AU - Cox, G AU - Mitchell, J B AU - Wink, D A AU - Russo, A AD - Radiation Biology Branch, NIH/National Cancer Institute, Building 10, Room B3-B69, Bethesda, MD 20892, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 268 EP - 276 VL - 30 IS - 3 SN - 0891-5849, 0891-5849 KW - Hydrazines KW - 0 KW - Lipopolysaccharides KW - Nitric Oxide Donors KW - Nitrites KW - PAPA NONOate KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Xanthine KW - 1AVZ07U9S7 KW - 2,3-diaminonaphthalene KW - 2BNZ6BRS87 KW - Nitric Oxide KW - 31C4KY9ESH KW - Interferon-gamma KW - 82115-62-6 KW - 2-Naphthylamine KW - CKR7XL41N4 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Index Medicus KW - Xanthine Oxidase -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Nitric Oxide Synthase -- deficiency KW - Nitrites -- metabolism KW - Xanthine -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Interferon-gamma -- pharmacology KW - Mice KW - Mice, Knockout KW - Oxidation-Reduction KW - Hydrazines -- pharmacology KW - Nitric Oxide Synthase -- physiology KW - Cell Line KW - Nitric Oxide Donors -- pharmacology KW - 2-Naphthylamine -- metabolism KW - Listeria monocytogenes -- drug effects KW - Macrophages -- microbiology KW - Listeria monocytogenes -- growth & development KW - Oxidative Stress KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- metabolism KW - 2-Naphthylamine -- analogs & derivatives KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70637859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Comparison+of+control+of+Listeria+by+nitric+oxide+redox+chemistry+from+murine+macrophages+and+NO+donors%3A+insights+into+listeriocidal+activity+of+oxidative+and+nitrosative+stress.&rft.au=Ogawa%2C+R%3BPacelli%2C+R%3BEspey%2C+M+G%3BMiranda%2C+K+M%3BFriedman%2C+N%3BKim%2C+S+M%3BCox%2C+G%3BMitchell%2C+J+B%3BWink%2C+D+A%3BRusso%2C+A&rft.aulast=Ogawa&rft.aufirst=R&rft.date=2001-02-01&rft.volume=30&rft.issue=3&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: signaling by BMPs and TGF-betas. AN - 70634568; 11169847 AB - The eight mammalian Smad proteins mediate cellular signaling from members of the transforming growth factor-beta (TGF-beta), bone morphogenetic protein (BMP), and activin families. Smads 1, 5, and 8 transmit signals from BMPs, while Smads 2 and 3 transmit signals from TGF-betas and activin. Smad 4 is a common mediator of both pathways, while Smads 6 and 7 inhibit signaling. Signal transduction involves translocation of Smad complexes to the nucleus and subsequent gene activation. Little is known about the expression of endogenous Smad proteins during development. We identified commercially available Smad antibodies that specifically recognize a unique Smad protein and are suitable for immunohistochemistry. Here we compare the localization of Smads 1, 2, 3, 4, 5, and 6 in tissues of the 15-day gestation mouse embryo. Immunoreactive Smad proteins are seen in many tissues with differences in the localization being dependent upon the cell type. All tissues express Smad 4 and at least one each of the BMP-specific and TGF-beta-specific Smads, while expression of Smad 6 is more restricted. Differences are observed in the nuclear versus cytoplasmic localization among the Smads in different cell types or tissues, suggesting selective activation of Smads during this stage of development. Copyright 2001 Wiley-Liss, Inc. JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Flanders, K C AU - Kim, E S AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. flanderk@dce41.nci.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 141 EP - 154 VL - 220 IS - 2 SN - 1058-8388, 1058-8388 KW - Bone Morphogenetic Proteins KW - 0 KW - DNA-Binding Proteins KW - Recombinant Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - COS Cells KW - Transfection KW - Humans KW - Gestational Age KW - Cercopithecus aethiops KW - Organ Specificity KW - Mice KW - Immunohistochemistry KW - Growth Plate -- embryology KW - Cell Line KW - Trans-Activators -- metabolism KW - Signal Transduction -- physiology KW - Embryo, Mammalian -- physiology KW - DNA-Binding Proteins -- analysis KW - Transforming Growth Factor beta -- physiology KW - Trans-Activators -- genetics KW - Embryo, Mammalian -- cytology KW - Bone Morphogenetic Proteins -- physiology KW - DNA-Binding Proteins -- genetics KW - Trans-Activators -- analysis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70634568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.atitle=Immunohistochemical+expression+of+Smads+1-6+in+the+15-day+gestation+mouse+embryo%3A+signaling+by+BMPs+and+TGF-betas.&rft.au=Flanders%2C+K+C%3BKim%2C+E+S%3BRoberts%2C+A+B&rft.aulast=Flanders&rft.aufirst=K&rft.date=2001-02-01&rft.volume=220&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.issn=10588388&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacology and effects of cannabis: a brief review. AN - 70632419; 11157422 AB - Increasing prevalence of recreational cannabis use among the young population has stimulated debate on the possible effects of acute and longterm use. To highlight recent knowledge of mechanisms of action, effects on psychomotor and cognitive performance, and health risks associated with cannabis consumption. A brief review of recent literature on the prevalence of recreational cannabis use, the potency of modern cannabis preparations and the pharmacological actions of cannabis. Cannabinoids derived from herbal cannabis interact with endogenous cannabinoid systems in the body. Actions on specific brain receptors cause dose-related impairments of psychomotor performance with implications for car and train driving, aeroplane piloting and academic performance. Other constituents of cannabis smoke carry respiratory and cardiovascular health risks similar to those of tobacco smoke. Cannabis is not, as widely perceived, a harmless drug but poses risks to the individual and to society. JF - The British journal of psychiatry : the journal of mental science AU - Ashton, C H AD - University of Newcastle upon Tyne, Department of Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP, UK. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 101 EP - 106 VL - 178 SN - 0007-1250, 0007-1250 KW - Cannabinoids KW - 0 KW - Psychotropic Drugs KW - Index Medicus KW - Humans KW - Respiratory Tract Diseases -- chemically induced KW - Marijuana Abuse -- epidemiology KW - Cognition Disorders -- chemically induced KW - Male KW - Female KW - Prevalence KW - Psychotropic Drugs -- pharmacology KW - Cannabinoids -- pharmacokinetics KW - Cannabinoids -- adverse effects KW - Psychotropic Drugs -- pharmacokinetics KW - Psychotropic Drugs -- adverse effects KW - Cannabis -- adverse effects KW - Cannabinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.atitle=Pharmacology+and+effects+of+cannabis%3A+a+brief+review.&rft.au=Ashton%2C+C+H&rft.aulast=Ashton&rft.aufirst=C&rft.date=2001-02-01&rft.volume=178&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.issn=00071250&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Br J Psychiatry. 2001 Sep;179:270-1 [11532812] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The neurotoxic prion peptide fragment PrP(106-126) is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1. AN - 70632277; 11160182 AB - Prion diseases are transmissible and fatal neurodegenerative disorders which involve infiltration and activation of mononuclear phagocytes at the brain lesions. A 20-aa acid fragment of the human cellular prion protein, PrP(106-126), was reported to mimic the biological activity of the pathologic isoform of prion and activates mononuclear phagocytes. The cell surface receptor(s) mediating the activity of PrP(106-126) is unknown. In this study, we show that PrP(106-126) is chemotactic for human monocytes through the use of a G protein-coupled receptor formyl peptide receptor-like 1 (FPRL1), which has been reported to interact with a diverse array of exogenous or endogenous ligands. Upon stimulation by PrP(106-126), FPRL1 underwent a rapid internalization and, furthermore, PrP(106-126) enhanced monocyte production of proinflammatory cytokines, which was inhibited by pertussis toxin. Thus, FPRL1 may act as a "pattern recognition" receptor that interacts with multiple pathologic agents and may be involved in the proinflammatory process of prion diseases. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Le, Y AU - Yazawa, H AU - Gong, W AU - Yu, Z AU - Ferrans, V J AU - Murphy, P M AU - Wang, J M AD - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick, Science Applications International Corporation-Frederick, Frederick, MD 21702, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 1448 EP - 1451 VL - 166 IS - 3 SN - 0022-1767, 0022-1767 KW - Chemotactic Factors KW - 0 KW - Cytokines KW - FPR2 protein, human KW - Ligands KW - Peptide Fragments KW - Prions KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Lipoxin KW - Receptors, Peptide KW - prion protein (106-126) KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cytokines -- biosynthesis KW - Humans KW - Rats KW - Tumor Cells, Cultured KW - Monocytes -- immunology KW - Microglia -- immunology KW - Monocytes -- metabolism KW - Inflammation -- immunology KW - Inflammation -- metabolism KW - Calcium Signaling -- immunology KW - Cell Line KW - Microglia -- metabolism KW - Prions -- toxicity KW - Chemotactic Factors -- toxicity KW - Peptide Fragments -- toxicity KW - Receptors, Peptide -- metabolism KW - Receptors, Immunologic -- physiology KW - Chemotactic Factors -- physiology KW - Receptors, Peptide -- physiology KW - Peptide Fragments -- agonists KW - Peptide Fragments -- physiology KW - Prions -- physiology KW - GTP-Binding Proteins -- metabolism KW - Receptors, Immunologic -- metabolism KW - Chemotaxis, Leukocyte -- immunology KW - Prions -- agonists KW - N-Formylmethionine Leucyl-Phenylalanine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=The+neurotoxic+prion+peptide+fragment+PrP%28106-126%29+is+a+chemotactic+agonist+for+the+G+protein-coupled+receptor+formyl+peptide+receptor-like+1.&rft.au=Le%2C+Y%3BYazawa%2C+H%3BGong%2C+W%3BYu%2C+Z%3BFerrans%2C+V+J%3BMurphy%2C+P+M%3BWang%2C+J+M&rft.aulast=Le&rft.aufirst=Y&rft.date=2001-02-01&rft.volume=166&rft.issue=3&rft.spage=1448&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated hepatic perfusion for unresectable hepatic metastases from colorectal cancer. AN - 70632081; 11174711 AB - Unresectable colorectal liver metastases are a significant clinical problem. Isolated hepatic perfusion (IHP) is a regional treatment technique that delivers high dose chemotherapy, biologic agents, and hyperthermia via a completely isolated vascular recirculating perfusion circuit as a means of regionally treating liver tumors. This study presents our results of IHP with tumor necrosis factor (TNF) plus melphalan or IHP with melphalan alone followed by infusional floxuridine (FUDR) and leucovorin in patients with advanced or refractory unresectable hepatic colorectal metastases. Fifty-one patients with unresectable colorectal hepatic metastases underwent a 60-minute IHP with 1.5 mg/kg melphalan and hyperthermia (39 degrees C to 40 degrees C). Thirty-two patients received IHP with 1 mg TNF with melphalan and 19 patients had IHP with melphalan alone followed by monthly hepatic intra-arterial infusional (HAI) FUDR (0.2 mg/kg/day) and leucovorin (15 mg/M(2)/day) for 14 days monthly for up to 12 months. Twenty-six patients failed 1 or more previous treatment regimens for established hepatic metastases and 27 had greater than 25% hepatic replacement (PHR) by tumor. Patients were monitored for response, toxicity, and survival. There was 1 perioperative death (2%), and only 2 patients (4%) had measurable perfusate leak during IHP (both less than 4%). In the 32 patients treated with IHP alone there were no detectable systemic TNF or melphalan levels during perfusion. The overall objective radiographic response rate (all partial [PR]) was 76% (38 of 50 assessable patients) with a median duration of 10.5 months (range, 2 to 21 months). Twenty-four of 31 patients (77%) had a PR after IHP alone and 14 of 19 (74%) after IHP with postperfusion HAI. Median duration of response was 8.5 months after IHP alone and 14.5 months after IHP and HAI; median survival was 16 and 27 months, respectively. There were 18 PRs in 26 patients (69%) whose prior therapy had failed and 18 PRs in 27 patients (67%) with PHR of 25 or greater. IHP can be performed with acceptably low morbidity and has significant antitumor activity in patients with unresectable hepatic metastases from colorectal cancer including those with refractory disease or PHR of 25 or greater. HAI appears to prolong the duration of response after IHP, and this combined treatment strategy deserves additional clinical evaluation as a therapeutic modality in this setting. JF - Surgery AU - Bartlett, D L AU - Libutti, S K AU - Figg, W D AU - Fraker, D L AU - Alexander, H R AD - Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 176 EP - 187 VL - 129 IS - 2 SN - 0039-6060, 0039-6060 KW - Tumor Necrosis Factor-alpha KW - 0 KW - Floxuridine KW - 039LU44I5M KW - Melphalan KW - Q41OR9510P KW - Leucovorin KW - Q573I9DVLP KW - Abridged Index Medicus KW - Index Medicus KW - Infusions, Intra-Arterial KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Leucovorin -- administration & dosage KW - Aged KW - Floxuridine -- administration & dosage KW - Melphalan -- administration & dosage KW - Adult KW - Hyperthermia, Induced KW - Tumor Necrosis Factor-alpha -- analysis KW - Neoplasm Metastasis KW - Middle Aged KW - Radiography KW - Melphalan -- blood KW - Female KW - Male KW - Survival Analysis KW - Liver Neoplasms -- therapy KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- therapy KW - Liver Neoplasms -- diagnostic imaging KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Liver Neoplasms -- secondary KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgery&rft.atitle=Isolated+hepatic+perfusion+for+unresectable+hepatic+metastases+from+colorectal+cancer.&rft.au=Bartlett%2C+D+L%3BLibutti%2C+S+K%3BFigg%2C+W+D%3BFraker%2C+D+L%3BAlexander%2C+H+R&rft.aulast=Bartlett&rft.aufirst=D&rft.date=2001-02-01&rft.volume=129&rft.issue=2&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Surgery&rft.issn=00396060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Choose and prepare foods with less salt: dietary advice for all Americans. AN - 70630623; 11160584 AB - The Nutrition and Your Health: Dietary Guidelines for Americans have included dietary guidance on salt and sodium since they were first released in 1980. This paper briefly reviews the impetus for including sodium guidelines, changes in them over time and factors influencing these changes. Although guidance appears to have changed little over the five editions, differences in wording reflect changes in knowledge of the link between sodium and blood pressure, a shift in public health policy toward prevention and increased consumption of processed and prepared foods. We examine methods to monitor sodium intake and assess whether Americans are following these guidelines. Available data indicate that American adolescents and adults are consuming more sodium than recommended and are unable to judge whether the amount of sodium in their diet is appropriate. Although Americans avoid adding salt to food at the table, their efforts may have little effect given that the majority of salt consumed is added during commercial processing and preparation. Thus, changes to the Dietary Guidelines that emphasize the major sources of sodium in U.S. diets and advice to "choose and prepare foods with less salt" may help all Americans meet recommended sodium intake levels in the future. JF - The Journal of nutrition AU - Loria, C M AU - Obarzanek, E AU - Ernst, N D AD - National Heart, Lung and Blood Institute, Bethesda, MD 20892-7934, USA. loriac@nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 536S EP - 551S VL - 131 IS - 2S-1 SN - 0022-3166, 0022-3166 KW - Sodium, Dietary KW - 0 KW - Index Medicus KW - United States KW - Hypertension -- chemically induced KW - Age Factors KW - Sex Factors KW - Food Preferences KW - Humans KW - Drug Monitoring KW - Mental Recall KW - Language KW - Blood Pressure -- drug effects KW - Food Handling -- standards KW - Sodium, Dietary -- adverse effects KW - Nutrition Policy KW - Food Handling -- methods KW - Sodium, Dietary -- administration & dosage KW - Nutrition Surveys KW - Sodium, Dietary -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70630623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Choose+and+prepare+foods+with+less+salt%3A+dietary+advice+for+all+Americans.&rft.au=Loria%2C+C+M%3BObarzanek%2C+E%3BErnst%2C+N+D&rft.aulast=Loria&rft.aufirst=C&rft.date=2001-02-01&rft.volume=131&rft.issue=2S-1&rft.spage=536S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased proliferative activity and programmed cellular death in the turkey hen pituitary gland following interruption of incubation behavior. AN - 70630588; 11159364 AB - Incubation behavior or broodiness in turkey hens is characterized by ovarian regression, hyperprolactinemia, and persistent nesting. Nest-deprivation of incubating turkey hens results in disruption of broodiness accompanied by a precipitous decline in plasma prolactin (PRL) concentrations. The objective of the present study is to examine cellular changes in the pituitary gland associated with nest-deprivation for 0, 1, 2, 3, 4, or 7 days. Bromodeoxyuridine (BrdU) was administered prior to kill to study proliferative activity. Pituitary tissue sections were immunostained using turkey growth hormone (GH) antibody, and/or chicken PRL peptide antibody, and BrdU antibody. Plasma PRL concentrations declined significantly following nest-deprivation for 1 or more days. The midsagittal pituitary area immunoreactive (ir) to GH was significantly increased while that of PRL was significantly decreased following nest-deprivation for 2 or more days. Terminal deoxy-UTP nick end labeling and PRL-immunostaining revealed an abundance of apoptotic nuclei in both cephalic and caudal lobes of the anterior pituitary gland, suggestive of programmed cellular death of lactotrophs in the pituitary gland of hens nest-deprived for 2 or more days. Mammosomatotrophs were abundant in hens nest-deprived on Day 0 but were absent in hens nest-deprived for 1 or more days. Proliferating (BrdU-ir) cells were significantly abundant in the pituitary cephalic and caudal lobes following nest-deprivation for 1 or more days but were absent on Day 0 or in laying hens. Dual-labeling studies indicated that most of the BrdU-ir nuclei in the caudal lobe were not colocalized in somatotrophs in hens nest-deprived for 1-4 days but did colocalize with GH following 7 days of nest-deprivation. In conclusion, nest-deprivation of incubating turkey hens results in 1) a precipitous decline in plasma PRL concentration, 2) programmed cell death of lactotrophs, 3) disappearance of mammosomatotrophs, 4) increased proliferative activity of pituitary cells, and 5) recruitment of somatotrophs arising primarily from mitosis of nonsomatotrophic cells. JF - Biology of reproduction AU - Ramesh, R AU - Kuenzel, W J AU - Proudman, J A AD - Germplasm and Gamete Physiology Laboratory, Agricultural Research Service, US Department of Agriculture, Beltsville, MD 20705, USA. rameshr@codon.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 611 EP - 618 VL - 64 IS - 2 SN - 0006-3363, 0006-3363 KW - Antimetabolites KW - 0 KW - Prolactin KW - 9002-62-4 KW - Growth Hormone KW - 9002-72-6 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Antimetabolites -- pharmacology KW - In Situ Nick-End Labeling KW - Animals KW - Bromodeoxyuridine -- pharmacology KW - Cell Differentiation -- physiology KW - Cell Division -- physiology KW - Immunohistochemistry KW - Growth Hormone -- metabolism KW - Female KW - Prolactin -- metabolism KW - Maternal Behavior -- physiology KW - Pituitary Gland -- anatomy & histology KW - Pituitary Gland -- physiology KW - Apoptosis -- physiology KW - Turkeys -- physiology KW - Pituitary Gland -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70630588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=Increased+proliferative+activity+and+programmed+cellular+death+in+the+turkey+hen+pituitary+gland+following+interruption+of+incubation+behavior.&rft.au=Ramesh%2C+R%3BKuenzel%2C+W+J%3BProudman%2C+J+A&rft.aulast=Ramesh&rft.aufirst=R&rft.date=2001-02-01&rft.volume=64&rft.issue=2&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. AN - 70630522; 11158311 AB - gadd153, also known as chop, is a highly stress-inducible gene that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER) (so-called ER stress). Although all reported types of ER stress induce expression of Gadd153, its role in the stress response has remained largely undefined. Several studies have correlated Gadd153 expression with cell death, but a mechanistic link between Gadd153 and apoptosis has never been demonstrated. To address this issue we employed a cell model system in which Gadd153 is constitutively overexpressed, as well as two cell lines in which Gadd153 expression is conditional. In all cell lines, overexpression of Gadd153 sensitized cells to ER stress. Investigation of the mechanisms contributing to this effect revealed that elevated Gadd153 expression results in the down-regulation of Bcl2 expression, depletion of cellular glutathione, and exaggerated production of reactive oxygen species. Restoration of Bcl2 expression in Gadd153-overexpressing cells led to replenishment of glutathione and a reduction in levels of reactive oxygen species, and it protected cells from ER stress-induced cell death. We conclude that Gadd153 sensitizes cells to ER stress through mechanisms that involve down-regulation of Bcl2 and enhanced oxidant injury. JF - Molecular and cellular biology AU - McCullough, K D AU - Martindale, J L AU - Klotz, L O AU - Aw, T Y AU - Holbrook, N J AD - Cell Stress and Aging Section, Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224-6825, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 1249 EP - 1259 VL - 21 IS - 4 SN - 0270-7306, 0270-7306 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DDIT3 protein, human KW - DNA Primers KW - Ddit3 protein, mouse KW - Proto-Oncogene Proteins c-bcl-2 KW - Transcription Factors KW - Transcription Factor CHOP KW - 147336-12-7 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - DNA Primers -- genetics KW - HeLa Cells KW - Glutathione -- metabolism KW - Humans KW - Gene Expression KW - Mice KW - Oxidation-Reduction KW - Mutagenesis, Site-Directed KW - Genes, bcl-2 KW - Base Sequence KW - Down-Regulation KW - Oxidative Stress KW - Cell Line KW - Endoplasmic Reticulum -- metabolism KW - Transcription Factors -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - CCAAT-Enhancer-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - CCAAT-Enhancer-Binding Proteins -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70630522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Gadd153+sensitizes+cells+to+endoplasmic+reticulum+stress+by+down-regulating+Bcl2+and+perturbing+the+cellular+redox+state.&rft.au=McCullough%2C+K+D%3BMartindale%2C+J+L%3BKlotz%2C+L+O%3BAw%2C+T+Y%3BHolbrook%2C+N+J&rft.aulast=McCullough&rft.aufirst=K&rft.date=2001-02-01&rft.volume=21&rft.issue=4&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1980 Jul 15;106(1):55-62 [7416469] Oncogene. 2000 Feb 10;19(6):745-53 [10698492] Mol Cell Biol. 1987 Jul;7(7):2610-3 [3475568] Am J Physiol. 1988 Dec;255(6 Pt 1):E801-5 [3202158] Mol Cell Biol. 1989 Oct;9(10):4196-203 [2573827] J Clin Invest. 1991 Jul;88(1):260-9 [1647417] Cancer Res. 1992 Jan 1;52(1):5-10 [1727386] Genes Dev. 1992 Mar;6(3):439-53 [1547942] Cell. 1992 Apr 3;69(1):119-28 [1555236] Mol Cell Biol. 1993 Aug;13(8):4736-44 [8336711] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6875-9 [8041712] J Biol Chem. 1994 Aug 5;269(31):20119-25 [8051100] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12967-71 [7809156] J Immunol. 1995 Apr 1;154(7):3194-203 [7897207] J Biol Chem. 1995 Apr 21;270(16):9526-34 [7721881] Biochem Biophys Res Commun. 1995 Nov 2;216(1):313-20 [7488106] Blood. 1995 Nov 15;86(10):3823-34 [7579350] Eur J Immunol. 1996 May;26(5):1164-9 [8647182] Biochem J. 1996 Mar 1;314 ( Pt 2):547-54 [8670069] Mol Cell Biol. 1996 Apr;16(4):1479-89 [8657121] J Biol Chem. 1996 Jun 14;271(24):14285-9 [8662954] J Biol Chem. 1996 Jun 28;271(26):15420-7 [8662848] Mol Cell Biol. 1996 Aug;16(8):4273-80 [8754828] Cancer Res. 1996 Jul 15;56(14):3250-6 [8764117] Surgery. 1996 Aug;120(2):150-7; discussion 157-8 [8751577] Cancer Res. 1996 Oct 1;56(19):4315-9 [8813114] Oncogene. 1996 Oct 17;13(8):1659-65 [8895511] FEBS Lett. 1996 Oct 21;395(2-3):143-7 [8898082] Cancer Res. 1997 Feb 15;57(4):686-95 [9044846] Cell. 1997 Feb 21;88(4):427-30 [9038332] J Biol Chem. 1997 Mar 14;272(11):7445-54 [9054446] J Biol Chem. 1997 Aug 29;272(35):21751-9 [9268304] Mol Cell Biol. 1997 Nov;17(11):6700-7 [9343434] Biochem Biophys Res Commun. 1998 Jan 6;242(1):1-9 [9439600] FASEB J. 1998 Apr;12(6):479-86 [9535220] Genes Dev. 1998 Apr 1;12(7):982-95 [9531536] Am J Physiol. 1998 Nov;275(5 Pt 1):L861-9 [9815102] Semin Liver Dis. 1998;18(4):415-24 [9875558] Genes Dev. 1999 May 15;13(10):1211-33 [10346810] FASEB J. 1999 Jul;13(10):1169-83 [10385608] Nat Med. 1999 Jul;5(7):745-51 [10395318] Physiol Rev. 1999 Jul;79(3):683-701 [10390516] J Biol Chem. 1999 Nov 19;274(47):33627-36 [10559251] Free Radic Biol Med. 1999 Nov;27(9-10):945-50 [10569627] Methods Enzymol. 1985;113:548-55 [4088074] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of beta1 integrins induces cell-cell adhesion. AN - 70630475; 11161706 AB - Integrins are highly regulated receptors that can function in both cell-substrate and cell-cell adhesion. We have found that the activating anti-beta1 mAb, 12G10, can specifically and rapidly induce both cell-substrate and cell-cell adhesion of HT-1080 human fibrosarcoma and other cell types. Binding of mAb 12G10 induced clustering of cell-surface integrins, and the preferential localization of beta1 integrins expressing the 12G10 epitope at cell-cell adhesion sites. Fab fragments of mAb 12G10 induced HT-1080 cell-cell adhesion as effectively as did intact antibodies, suggesting that integrin clustering was not due to direct antibody crosslinking. Latrunculin B, an inhibitor of F-actin polymerization, inhibited cell-cell adhesion but not the clustering of integrins. Results from a novel, two-color cell-cell adhesion assay suggested that nonactivated cells can bind to activated cells and that integrin activation-induced HT-1080 cell-cell adhesion minimally requires the interaction of activated alpha2beta1 with nonactivated alpha3beta1. These findings suggest that HT-1080 cell-cell adhesion induced by integrin activation require a signaling process involving integrin clustering and the subsequent organization of the cytoskeleton. Integrin activation could therefore play a key role in cell-cell adhesion. JF - Experimental cell research AU - Whittard, J D AU - Akiyama, S K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 65 EP - 76 VL - 263 IS - 1 SN - 0014-4827, 0014-4827 KW - Actins KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD29 KW - Bridged Bicyclo Compounds, Heterocyclic KW - Cadherins KW - Cations, Divalent KW - Epitopes KW - Fibronectins KW - Laminin KW - Thiazoles KW - Thiazolidines KW - Collagen KW - 9007-34-5 KW - latrunculin B KW - LW7U308U7U KW - Index Medicus KW - Microscopy, Confocal KW - Fibrosarcoma KW - Laminin -- metabolism KW - Cations, Divalent -- metabolism KW - Hybridomas KW - Cadherins -- metabolism KW - Antibodies, Monoclonal -- metabolism KW - Collagen -- metabolism KW - Humans KW - Actins -- metabolism KW - Fibronectins -- metabolism KW - Models, Biological KW - Antibodies, Monoclonal -- immunology KW - Thiazoles -- pharmacology KW - Bridged Bicyclo Compounds, Heterocyclic -- pharmacology KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Immunologic KW - Immunohistochemistry KW - Signal Transduction KW - Antigens, CD29 -- immunology KW - Cell Adhesion -- physiology KW - Antigens, CD29 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70630475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Activation+of+beta1+integrins+induces+cell-cell+adhesion.&rft.au=Whittard%2C+J+D%3BAkiyama%2C+S+K&rft.aulast=Whittard&rft.aufirst=J&rft.date=2001-02-01&rft.volume=263&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel-induced immune suppression is associated with NF-kappaB activation via conventional PKC isotypes in lipopolysaccharide-stimulated 70Z/3 pre-B lymphocyte tumor cells. AN - 70628515; 11160860 AB - Paclitaxel, a potent antitumor agent, has been shown to be lipopolysaccharide (LPS) mimetic in mice, stimulating signaling pathways and gene expression indistinguishably from LPS. In the present study, we showed the intracellular signaling pathway of paclitaxel-induced nuclear factor-kappaB (NF-kappaB) activation and its suppressive effect on LPS-induced signaling in murine 70Z/3 pre-B cells. Stimulation of 70Z/3 cells with LPS for 30 min caused activation of NF-kappaB in the nuclei by detection of DNA-protein binding specific to NF-kappaB. Similarly, paclitaxel also produced a marked and dose-related NF-kappaB activation. However, pretreatment of cells with 10 microM paclitaxel for 18 h resulted in complete inhibition of LPS-mediated NF-kappaB activation. Interestingly, the activity of IkappaB kinase (IKK-beta), which plays an essential role in NF-kappaB activation through IkappaB phosphorylation, was largely enhanced in paclitaxel-treated cells, detected as IkappaBalpha phosphorylation. Because protein kinase C (PKC) is implicated in the activation of NF-kappaB via IKK-beta, the effect of paclitaxel on PKC activation was also measured. It was shown that NF-kappaB nuclear translocation and DNA binding in response to paclitaxel was completely blocked by the conventional PKC inhibitor, Gö 6976. Moreover, immunoblotting analysis with paclitaxel-treated cell extract demonstrated that the conventional PKC isotype PKC-alpha was found to be involved in the regulation of paclitaxel-induced NF-kappaB activation, as determined by electrophoretic mobility shift of PKC. Therefore, these data suggest that paclitaxel may activate IKK-beta via conventional PKC isotypes, resulting in NF-kappaB activation and, finally, desensitization of LPS-inducible signaling pathway in 70Z/3 pre-B cells. JF - Molecular pharmacology AU - Lee, M AU - Jeon, Y J AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA. leemi@mail.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 248 EP - 253 VL - 59 IS - 2 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - I-kappa B Proteins KW - Isoenzymes KW - Lipopolysaccharides KW - NF-kappa B KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Chuk protein, mouse KW - EC 2.7.11.10 KW - I-kappa B Kinase KW - Ikbkb protein, mouse KW - Ikbke protein, mouse KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C beta KW - Protein Kinase C-alpha KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Drug Interactions KW - Protein-Serine-Threonine Kinases -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Enzyme Activation KW - I-kappa B Proteins -- metabolism KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Mice KW - Protein Kinase C -- metabolism KW - B-Lymphocytes -- drug effects KW - Lipopolysaccharides -- pharmacology KW - Paclitaxel -- pharmacology KW - B-Lymphocytes -- immunology KW - B-Lymphocytes -- enzymology KW - Isoenzymes -- metabolism KW - NF-kappa B -- metabolism KW - Immunosuppression UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70628515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Paclitaxel-induced+immune+suppression+is+associated+with+NF-kappaB+activation+via+conventional+PKC+isotypes+in+lipopolysaccharide-stimulated+70Z%2F3+pre-B+lymphocyte+tumor+cells.&rft.au=Lee%2C+M%3BJeon%2C+Y+J&rft.aulast=Lee&rft.aufirst=M&rft.date=2001-02-01&rft.volume=59&rft.issue=2&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in Apc(Min)/+ mice. AN - 70628211; 11181458 AB - The proteins encoded by BRCA1 and ATM may be important in DNA repair and maintenance of genomic integrity. Women heterozygous for a mutation in BRCA1 have an increased incidence of breast cancer. Some evidence also suggests that female carriers of ATM mutations may be susceptible to breast cancer. However, mice carrying one mutant allele of Brca1 or ATM are not highly susceptible to breast cancer. We proposed that heterozygosity for a mutant allele of Brca1 or ATM may confer a decreased ability to repair DNA damage. Such a defect might lead to a heightened sensitivity to tumor development in susceptible animal models. Therefore, mice predispose to mammary tumor development might show an increased susceptibility if they also carry an ATM or Brca1 mutation. C57BL/6J (B6) MIN/+ mice are predisposed to mammary and intestinal tumors and exposure to the point mutagen ethylnitrosourea (ENU) markedly increases mammary tumor multiplicity and incidence. To test our hypothesis, B6.MIN/+ male mice were crossed with 129S6/SvEvTac females heterozygous for a mutant allele of either Brca1 or ATM. Female progeny from each cross were treated with ENU and followed for tumor development. Only MIN/+ F1 females developed mammary tumors and heterozygosity for a mutant Brca1 or ATM allele had no effect on mammary or intestinal tumor incidence and multiplicity. These results suggest that heterozygosity for a mutation in Brca1 or ATM: does not affect MIN-induced tumorigenesis in mice under these conditions. Additionally, exposure to a somatic point mutagen does not increase tumor development in mice carrying Brca1 or ATM mutations. JF - Carcinogenesis AU - Karabinis, M E AU - Larson, D AU - Barlow, C AU - Wynshaw-Boris, A AU - Moser, A R AD - Laboratory of Genetics and Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53792, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD , USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 343 EP - 346 VL - 22 IS - 2 SN - 0143-3334, 0143-3334 KW - Cell Cycle Proteins KW - 0 KW - DNA Primers KW - DNA-Binding Proteins KW - Tumor Suppressor Proteins KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - Atm protein, mouse KW - Protein-Serine-Threonine Kinases KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Phenotype KW - Polymerase Chain Reaction KW - Animals KW - Incidence KW - Mice KW - Female KW - Mice, Knockout KW - DNA Primers -- chemistry KW - Mammary Neoplasms, Experimental -- chemically induced KW - Ethylnitrosourea -- toxicity KW - Genes, BRCA1 -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Protein-Serine-Threonine Kinases -- genetics KW - Loss of Heterozygosity -- genetics KW - Genetic Predisposition to Disease KW - Mutation KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70628211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Heterozygosity+for+a+mutation+in+Brca1+or+Atm+does+not+increase+susceptibility+to+ENU-induced+mammary+tumors+in+Apc%28Min%29%2F%2B+mice.&rft.au=Karabinis%2C+M+E%3BLarson%2C+D%3BBarlow%2C+C%3BWynshaw-Boris%2C+A%3BMoser%2C+A+R&rft.aulast=Karabinis&rft.aufirst=M&rft.date=2001-02-01&rft.volume=22&rft.issue=2&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells. AN - 70626491; 11158054 AB - Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. Although effective therapies exist for well differentiated tumors, the treatment options for poorly differentiated and anaplastic tumors are much less effective. In the present study we demonstrate that the thyroglobulin (Tg) promoter can be used to direct specific expression of either luciferase or thymidine kinase in thyroid cancer cells. Furthermore, using a putative enhancer element for the Tg gene, the activity of the Tg promoter in and its specificity for thyroid cells were enhanced. In transient transfectants or in stably transfected thyroid carcinoma cells, treatment with the histone deacetylase inhibitors, depsipeptide (FR9012228) and sodium butyrate, alone or in combination with 8-bromo-cAMP, resulted in further enhancement. In experiments in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the Tg promoter and the putative enhancer, HSV-TK expression and ganciclovir sensitivity were augmented. Similar results were obtained in two cell lines derived from a follicular thyroid carcinoma and in two anaplastic thyroid carcinoma cell lines. In summary, we report the construction of a suicide HSV-TK vector with preferential toxicity for thyroid cells. The results in anaplastic thyroid carcinoma cells suggest that it may be of use in the full spectrum of thyroid malignancies. JF - The Journal of clinical endocrinology and metabolism AU - Kitazono, M AU - Chuman, Y AU - Aikou, T AU - Fojo, T AD - Medicine Branch, DCS, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. kita@box-k.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 834 EP - 840 VL - 86 IS - 2 SN - 0021-972X, 0021-972X KW - Anti-Bacterial Agents KW - 0 KW - Antibiotics, Antineoplastic KW - Butyrates KW - Depsipeptides KW - Histone Deacetylase Inhibitors KW - Peptides, Cyclic KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Thyroglobulin KW - 9010-34-8 KW - romidepsin KW - CX3T89XQBK KW - Cyclic AMP KW - E0399OZS9N KW - Luciferases KW - EC 1.13.12.- KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Abridged Index Medicus KW - Index Medicus KW - Butyrates -- pharmacology KW - Humans KW - Adenocarcinoma, Follicular -- drug therapy KW - Reverse Transcriptase Polymerase Chain Reaction KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Transfection -- methods KW - Tumor Cells, Cultured KW - Carcinoma -- pathology KW - Carcinoma -- drug therapy KW - Enhancer Elements, Genetic KW - Simplexvirus -- genetics KW - Adenocarcinoma, Follicular -- pathology KW - Genes, Reporter KW - Luciferases -- genetics KW - Thymidine Kinase -- genetics KW - Promoter Regions, Genetic KW - Genetic Vectors KW - Thyroid Neoplasms -- drug therapy KW - Genetic Therapy -- methods KW - Thyroid Neoplasms -- pathology KW - Cyclic AMP -- physiology KW - Anti-Bacterial Agents -- toxicity KW - Antibiotics, Antineoplastic -- toxicity KW - Thyroglobulin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70626491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Construction+of+gene+therapy+vectors+targeting+thyroid+cells%3A+enhancement+of+activity+and+specificity+with+histone+deacetylase+inhibitors+and+agents+modulating+the+cyclic+adenosine+3%27%2C5%27-monophosphate+pathway+and+demonstration+of+activity+in+follicular+and+anaplastic+thyroid+carcinoma+cells.&rft.au=Kitazono%2C+M%3BChuman%2C+Y%3BAikou%2C+T%3BFojo%2C+T&rft.aulast=Kitazono&rft.aufirst=M&rft.date=2001-02-01&rft.volume=86&rft.issue=2&rft.spage=834&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Family history influence on drug abuse severity and treatment outcome. AN - 70622888; 11164690 AB - Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment. JF - Drug and alcohol dependence AU - Pickens, R W AU - Preston, K L AU - Miles, D R AU - Gupman, A E AU - Johnson, E O AU - Newlin, D B AU - Soriano, J AU - van den Bree, M B AU - Umbricht, A AD - Clinical Neurogenetics Section and Treatment Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. rpickens@hsc.vcu.edu Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 261 EP - 270 VL - 61 IS - 3 SN - 0376-8716, 0376-8716 KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Logistic Models KW - Humans KW - Chi-Square Distribution KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Substance-Related Disorders -- genetics KW - Male KW - Female KW - Methadone -- therapeutic use KW - Cocaine-Related Disorders -- genetics KW - Heroin Dependence -- urine KW - Narcotics -- therapeutic use KW - Heroin Dependence -- rehabilitation KW - Parents KW - Heroin Dependence -- genetics KW - Cocaine-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70622888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Family+history+influence+on+drug+abuse+severity+and+treatment+outcome.&rft.au=Pickens%2C+R+W%3BPreston%2C+K+L%3BMiles%2C+D+R%3BGupman%2C+A+E%3BJohnson%2C+E+O%3BNewlin%2C+D+B%3BSoriano%2C+J%3Bvan+den+Bree%2C+M+B%3BUmbricht%2C+A&rft.aulast=Pickens&rft.aufirst=R&rft.date=2001-02-01&rft.volume=61&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic requirement of p47phox for superoxide production by murine microglia. AN - 70616397; 11156938 AB - An NADPH oxidase is thought to function in microglial cells of the central nervous system. These conclusions are based on pharmacological and immunochemical evidence, although these approaches are indirect and raise issues of specificity. For example, diphenyleneiodonium inhibits a variety of flavoenzymes, including xanthine oxidase, NADH dehydrogenase, and NADPH oxidase. Here, we provide genetic evidence that p47phox, an essential component of the phagocyte NADPH oxidase, is required for superoxide anion release from microglia. Microglia derived from newborn wild-type mice, but not from newborn p47phox-deficient (knockout; -/-) mice, produced superoxide after stimulation by opsonized zymosan or phorbol myristate acetate. Endogenous p47phox was detected only in wild-type microglia, consistent with selective superoxide production in these cells. Superoxide release was restored in p47phox-deficient microglia that were retrovirally transduced with human p47phox cDNA. Similar kinetics of superoxide generation were observed, consistent with the same enzyme functioning in wild-type and restored microglia. Immuno-detection of p47phox in transduced cells confirmed that restoration of superoxide release correlated with production of recombinant protein. These data provide genetic proof that p47phox is necessary for superoxide release by microglial cells and indicate that a system related to the phagocyte oxidase is active in these cells. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Lavigne, M C AU - Malech, H L AU - Holland, S M AU - Leto, T L AD - Laboratory of Host Defenses, NIAID, NIH, Bethesda, MD 20892, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 285 EP - 287 VL - 15 IS - 2 SN - 0892-6638, 0892-6638 KW - Phosphoproteins KW - 0 KW - Recombinant Proteins KW - Superoxides KW - 11062-77-4 KW - Zymosan KW - 9010-72-4 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - NADPH Dehydrogenase KW - EC 1.6.99.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Zymosan -- pharmacology KW - Mice KW - Mice, Knockout KW - Animals, Newborn KW - NADPH Dehydrogenase -- metabolism KW - Nerve Degeneration KW - Cells, Cultured KW - Luminescent Measurements KW - Recombinant Proteins -- metabolism KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Phosphoproteins -- deficiency KW - Superoxides -- metabolism KW - Microglia -- physiology KW - Phosphoproteins -- genetics KW - Microglia -- cytology KW - Microglia -- drug effects KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70616397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Genetic+requirement+of+p47phox+for+superoxide+production+by+murine+microglia.&rft.au=Lavigne%2C+M+C%3BMalech%2C+H+L%3BHolland%2C+S+M%3BLeto%2C+T+L&rft.aulast=Lavigne&rft.aufirst=M&rft.date=2001-02-01&rft.volume=15&rft.issue=2&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Danger signals: SOS to the immune system. AN - 70591080; 11154927 AB - The activation of dendritic cells, necessary for the initiation of primary and secondary immune responses, can be induced by endogenous danger signals - released by tissues undergoing stress, damage or abnormal death - and also by exogenous danger signals elaborated by pathogens. Some endogenous danger signals that recently have been discovered are heat-shock proteins, nucleotides, reactive oxygen intermediates, extracellular-matrix breakdown products, neuromediators and cytokines like the IFNs. We propose that allergy may be initiated by the direct damage of dendritic or other cells by toxic chemicals and allergenic proteases, and suggest that the triggering of danger signal receptors by exogenous pathogen-derived molecules may be more to the advantage of the pathogen than to the host. JF - Current opinion in immunology AU - Gallucci, S AU - Matzinger, P AD - Ghost Laboratory, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 111, Bethesda, MD 20892, USA. sgallucci@niaid.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 114 EP - 119 VL - 13 IS - 1 SN - 0952-7915, 0952-7915 KW - Index Medicus KW - Animals KW - Models, Immunological KW - Antigen-Presenting Cells -- microbiology KW - Humans KW - Antigen-Presenting Cells -- immunology KW - Immune System -- pathology KW - Immune System -- secretion KW - Signal Transduction -- immunology KW - Immune System -- microbiology KW - Immune System -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70591080?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+immunology&rft.atitle=Danger+signals%3A+SOS+to+the+immune+system.&rft.au=Gallucci%2C+S%3BMatzinger%2C+P&rft.aulast=Gallucci&rft.aufirst=S&rft.date=2001-02-01&rft.volume=13&rft.issue=1&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+immunology&rft.issn=09527915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings. AN - 70589472; 11177119 AB - Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT. JF - Archives of general psychiatry AU - Daly, R C AU - Su, T P AU - Schmidt, P J AU - Pickar, D AU - Murphy, D L AU - Rubinow, D R AD - Behavioral Endocrinology Branch, National Institute of Mental Health, Bldg 10, Room 3N242, 10 Center Dr, MSC 1277, Bethesda, MD 20892-1277, USA. dalyr@intra.nimh.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 172 EP - 177 VL - 58 IS - 2 SN - 0003-990X, 0003-990X KW - Anabolic Agents KW - 0 KW - Neuropeptides KW - Neurotransmitter Agents KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Methyltestosterone KW - V9EFU16ZIF KW - Abridged Index Medicus KW - Index Medicus KW - Neurotransmitter Agents -- cerebrospinal fluid KW - Aggression -- drug effects KW - Libido -- drug effects KW - Affect -- drug effects KW - Sleep -- drug effects KW - Neuropeptides -- cerebrospinal fluid KW - Humans KW - Adult KW - Adolescent KW - Male KW - Sexual Behavior -- drug effects KW - Behavioral Symptoms -- cerebrospinal fluid KW - Behavioral Symptoms -- chemically induced KW - Anabolic Agents -- pharmacology KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Methyltestosterone -- metabolism KW - Brain Chemistry -- drug effects KW - Methyltestosterone -- pharmacology KW - Methyltestosterone -- adverse effects KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Anabolic Agents -- metabolism KW - Anabolic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70589472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Cerebrospinal+fluid+and+behavioral+changes+after+methyltestosterone+administration%3A+preliminary+findings.&rft.au=Daly%2C+R+C%3BSu%2C+T+P%3BSchmidt%2C+P+J%3BPickar%2C+D%3BMurphy%2C+D+L%3BRubinow%2C+D+R&rft.aulast=Daly&rft.aufirst=R&rft.date=2001-02-01&rft.volume=58&rft.issue=2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. AN - 70588285; 11219769 AB - Bladder cancer is the sixth most common cancer in the United States. The main identified risk factor is cigarette smoking, which is estimated to contribute to up to 50% of new cases in men and 20% in women. Besides containing other carcinogens, cigarette smoke is a rich source of reactive oxygen species (ROS) that can induce a variety of DNA damage, some of which is repaired by the base excision repair (BER) pathway. The XRCC1 gene protein plays an important role in BER by serving as a scaffold for other repair enzymes and by recognizing single-strand DNA breaks. Three polymorphisms that induce amino acid changes have been found in codon 194 (exon 6), codon 280 (exon 9), and codon 399 (exon 10) of this gene. We tested whether polymorphisms in XRCC1 were associated with bladder cancer risk and whether this association was modified by cigarette smoking. Therefore, we genotyped for the three polymorphisms in 235 bladder cancer cases and 213 controls who had been frequency matched to cases on age, sex, and ethnicity. We found no evidence of an association between the codon 280 variant and bladder cancer risk [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.6-2.6]. We found some evidence of a protective effect for subjects that carried at least one copy of the codon 194 variant allele relative to those homozygous for the common allele (OR, 0.59; 95% CI, 0.3-1.0). The combined analysis with smoking history suggested a possible gene-exposure interaction; however, the results were not statistically significant. Similarly, for the codon 399 polymorphism, our data suggested a protective effect of the homozygous variant genotype relative to carriers of either one or two copies of the common allele (OR, 0.70; 95% CI, 0.4-1.3), and provided limited evidence, albeit not statistically significant, for a gene-smoking interaction. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Stern, M C AU - Umbach, D M AU - van Gils, C H AU - Lunn, R M AU - Taylor, J A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, 27709, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 125 EP - 131 VL - 10 IS - 2 SN - 1055-9965, 1055-9965 KW - DNA-Binding Proteins KW - 0 KW - X-ray repair cross complementing protein 1 KW - Index Medicus KW - Reference Values KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Incidence KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Sex Distribution KW - Male KW - Female KW - Age Distribution KW - DNA Repair -- genetics KW - Polymorphism, Genetic KW - Urinary Bladder Neoplasms -- epidemiology KW - Urinary Bladder Neoplasms -- genetics KW - DNA-Binding Proteins -- genetics KW - Smoking -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70588285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=DNA+repair+gene+XRCC1+polymorphisms%2C+smoking%2C+and+bladder+cancer+risk.&rft.au=Stern%2C+M+C%3BUmbach%2C+D+M%3Bvan+Gils%2C+C+H%3BLunn%2C+R+M%3BTaylor%2C+J+A&rft.aulast=Stern&rft.aufirst=M&rft.date=2001-02-01&rft.volume=10&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Molecular mechanism of inactivation of TGF-beta receptors during carcinogenesis]. AN - 70586167; 11211784 JF - Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute. kims@dce41.nci.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 111 EP - 116 VL - 46 IS - 2 SN - 0039-9450, 0039-9450 KW - EWS-FLI fusion protein KW - 0 KW - Oncogene Proteins, Fusion KW - Proto-Oncogene Protein c-fli-1 KW - RNA-Binding Protein EWS KW - Receptors, Transforming Growth Factor beta KW - Transcription Factors KW - Transforming Growth Factor beta KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - transforming growth factor-beta type II receptor KW - Index Medicus KW - Transcription Factors -- physiology KW - Signal Transduction -- physiology KW - Oncogene Proteins, Fusion -- physiology KW - Transforming Growth Factor beta -- physiology KW - Humans KW - Transcription, Genetic KW - Protein-Serine-Threonine Kinases -- genetics KW - Gene Deletion KW - Receptors, Transforming Growth Factor beta -- genetics KW - Receptors, Transforming Growth Factor beta -- physiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70586167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tanpakushitsu+kakusan+koso.+Protein%2C+nucleic+acid%2C+enzyme&rft.atitle=%5BMolecular+mechanism+of+inactivation+of+TGF-beta+receptors+during+carcinogenesis%5D.&rft.au=Kim%2C+S+J&rft.aulast=Kim&rft.aufirst=S&rft.date=2001-02-01&rft.volume=46&rft.issue=2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Tanpakushitsu+kakusan+koso.+Protein%2C+nucleic+acid%2C+enzyme&rft.issn=00399450&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Time trends in exposure measurements from OSHA compliance inspections of the pulp and paper industry. AN - 70586074; 11217721 AB - Time trends in employee exposures to the air contaminants measured by the Occupational Safety and Health Administration (OSHA) during compliance inspections of pulp and paper manufacturing facilities conducted between 1979 and 1997 were evaluated based on the measurement results stored in the OSHA Integrated Management Information System (IMIS) database. The IMIS database is among the largest sources of occupational exposure measurements available for occupational health research in the United States. The IMIS database contains the results of 3,568 personal time-weighted average (TWA) measurements for 171 air contaminants made at 524 establishments in Standard Industrial Classification (SIC) 26. An analysis of these measurements revealed an overall decrease in the total number of measurements made per year since 1991, and a decrease in the percentage of measurements by year that exceeded the OSHA permissible exposure limits (PELs). Linear regression analyses detected decreasing trends in the geometric mean concentrations by year for 33 of the 36 agents analyzed. JF - Applied occupational and environmental hygiene AU - Coble, J B AU - Lees, P S AU - Matanoski, G AD - National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 263 EP - 270 VL - 16 IS - 2 SN - 1047-322X, 1047-322X KW - Air Pollutants, Occupational KW - 0 KW - Index Medicus KW - United States KW - Regression Analysis KW - Maximum Allowable Concentration KW - Humans KW - Retrospective Studies KW - Time Factors KW - Safety Management -- statistics & numerical data KW - Paper KW - Occupational Exposure -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70586074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+occupational+and+environmental+hygiene&rft.atitle=Time+trends+in+exposure+measurements+from+OSHA+compliance+inspections+of+the+pulp+and+paper+industry.&rft.au=Coble%2C+J+B%3BLees%2C+P+S%3BMatanoski%2C+G&rft.aulast=Coble&rft.aufirst=J&rft.date=2001-02-01&rft.volume=16&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Applied+occupational+and+environmental+hygiene&rft.issn=1047322X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for a gender-related effect of alcoholism on brain volumes. AN - 70585961; 11156801 AB - The goal of this study was to compare brain volumes of alcoholic and nonalcoholic men and women and determine if the magnitudes of differences in brain volumes between alcoholic women and nonalcoholic women are greater than the magnitudes of the differences between alcoholic men and nonalcoholic men. The study group included 118 subjects: 79 inpatients 30-60 years of age who were alcohol dependent but had no clinically apparent cognitive impairment or medical illness (43 men and 36 women) and 39 healthy comparison subjects of similar age who were not alcoholic (20 men and 19 women). The volume of intracranial contents was segmented into gray matter, white matter, sulcal CSF, and ventricular CSF from a T(1)-weighted magnetic resonance image obtained after the alcoholic subjects had attained 3 weeks of sobriety. Alcoholic women had significantly smaller volumes of gray and white matter as well as greater volumes of sulcal and ventricular CSF than nonalcoholic women. The differences in gray and white matter volumes between alcoholic and nonalcoholic men were significant, but the significance of these differences was of a smaller magnitude than the significance of the differences between alcoholic and nonalcoholic women. Direct comparisons of alcoholic men and women showed that the proportion of intracranial contents occupied by gray matter was smaller in alcoholic women than in alcoholic men. The magnitudes of differences in brain volumes adjusted for intracranial size between alcoholic women and nonalcoholic women were greater than the magnitudes of the adjusted differences between alcoholic men and nonalcoholic men. These results are consistent with greater sensitivity to alcohol neurotoxicity among women. JF - The American journal of psychiatry AU - Hommer, D AU - Momenan, R AU - Kaiser, E AU - Rawlings, R AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-1256, USA. danh@lcs.niaaa.nih.gov Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 198 EP - 204 VL - 158 IS - 2 SN - 0002-953X, 0002-953X KW - Ethanol KW - 3K9958V90M KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Adult KW - Skull -- anatomy & histology KW - Male KW - Female KW - Ethanol -- adverse effects KW - Ethanol -- pharmacology KW - Alcoholism -- diagnosis KW - Brain -- drug effects KW - Brain -- anatomy & histology KW - Alcohol Drinking -- adverse effects KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70585961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Evidence+for+a+gender-related+effect+of+alcoholism+on+brain+volumes.&rft.au=Hommer%2C+D%3BMomenan%2C+R%3BKaiser%2C+E%3BRawlings%2C+R&rft.aulast=Hommer&rft.aufirst=D&rft.date=2001-02-01&rft.volume=158&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-08 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inactivation of DNA mismatch repair by increased expression of yeast MLH1. AN - 70566375; 11154280 AB - Inactivation of DNA mismatch repair by mutation or by transcriptional silencing of the MLH1 gene results in genome instability and cancer predisposition. We recently found (P. V. Shcherbakova and T. A. Kunkel, Mol. Cell. Biol. 19:3177-3183, 1999) that an elevated spontaneous mutation rate can also result from increased expression of yeast MLH1. Here we investigate the mechanism of this mutator effect. Hybridization of poly(A)(+) mRNA to DNA microarrays containing 96.4% of yeast open reading frames revealed that MLH1 overexpression did not induce changes in expression of other genes involved in DNA replication or repair. MLH1 overexpression strongly enhanced spontaneous mutagenesis in yeast strains with defects in the 3'-->5' exonuclease activity of replicative DNA polymerases delta and epsilon but did not enhance the mutation rate in strains with deletions of MSH2, MLH1, or PMS1. This suggests that overexpression of MLH1 inactivates mismatch repair of replication errors. Overexpression of the PMS1 gene alone caused a moderate increase in the mutation rate and strongly suppressed the mutator effect caused by MLH1 overexpression. The mutator effect was also reduced by a missense mutation in the MLH1 gene that disrupted Mlh1p-Pms1p interaction. Analytical ultracentrifugation experiments showed that purified Mlh1p forms a homodimer in solution, albeit with a K(d) of 3.14 microM, 36-fold higher than that for Mlh1p-Pms1p heterodimerization. These observations suggest that the mismatch repair defect in cells overexpressing MLH1 results from an imbalance in the levels of Mlh1p and Pms1p and that this imbalance might lead to formation of nonfunctional mismatch repair complexes containing Mlh1p homodimers. JF - Molecular and cellular biology AU - Shcherbakova, P V AU - Hall, M C AU - Lewis, M S AU - Bennett, S E AU - Martin, K J AU - Bushel, P R AU - Afshari, C A AU - Kunkel, T A AD - Laboratories of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/02// PY - 2001 DA - February 2001 SP - 940 EP - 951 VL - 21 IS - 3 SN - 0270-7306, 0270-7306 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Carrier Proteins KW - DNA Primers KW - Fungal Proteins KW - MLH1 protein, S cerevisiae KW - PMS1 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - MutL Protein Homolog 1 KW - EC 3.6.1.3 KW - MutL Proteins KW - Index Medicus KW - Carrier Proteins -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Carrier Proteins -- chemistry KW - Genes, Fungal KW - DNA Primers -- genetics KW - Gene Silencing KW - Carrier Proteins -- genetics KW - Dimerization KW - Gene Expression KW - Amino Acid Sequence KW - Genome, Fungal KW - Protein Structure, Quaternary KW - Phenotype KW - Base Sequence KW - Molecular Sequence Data KW - Suppression, Genetic KW - Sequence Homology, Amino Acid KW - Mutation KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - DNA Repair KW - Base Pair Mismatch KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70566375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Inactivation+of+DNA+mismatch+repair+by+increased+expression+of+yeast+MLH1.&rft.au=Shcherbakova%2C+P+V%3BHall%2C+M+C%3BLewis%2C+M+S%3BBennett%2C+S+E%3BMartin%2C+K+J%3BBushel%2C+P+R%3BAfshari%2C+C+A%3BKunkel%2C+T+A&rft.aulast=Shcherbakova&rft.aufirst=P&rft.date=2001-02-01&rft.volume=21&rft.issue=3&rft.spage=940&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2001-02-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1997 Oct 24;278(5338):680-6 [9381177] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8568-73 [9671718] Nucleic Acids Res. 1998 Feb 15;26(4):948-53 [9461452] J Biol Chem. 1998 Apr 17;273(16):9837-41 [9545323] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8698-702 [9671741] Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12404-9 [9770499] Yeast. 1998 Sep 30;14(13):1209-21 [9791892] Curr Biol. 2000 Feb 10;10(3):145-8 [10679328] Nat Genet. 2000 Jan;24(1):27-35 [10615123] Oncogene. 1998 Nov 5;17(18):2413-7 [9811473] J Biol Chem. 2000 May 26;275(21):15728-32 [10748105] J Biol Chem. 2000 Jun 16;275(24):18424-31 [10747992] Genetics. 2000 Aug;155(4):1623-32 [10924461] Eur J Biochem. 1986 May 15;157(1):169-80 [3709531] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9473-7 [1658784] Biochemistry. 1991 Dec 17;30(50):11707-19 [1721535] EMBO J. 1993 Apr;12(4):1467-73 [8385605] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] Science. 1994 Aug 19;265(5175):1091-3 [8066446] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1950-4 [7892206] Cancer Res. 1995 Dec 15;55(24):6092-6 [8521398] Genes Dev. 1996 Jun 15;10(12):1433-42 [8666228] Eur J Biochem. 1996 Jun 1;238(2):297-307 [8681938] Annu Rev Biochem. 1996;65:101-33 [8811176] Mol Gen Genet. 1996 Sep 13;252(3):275-83 [8842147] Cell. 1996 Oct 4;87(1):65-73 [8858149] Cancer Res. 1997 Mar 1;57(5):808-11 [9041175] Cell. 1998 Nov 13;95(4):541-52 [9827806] Cancer Res. 1999 Jan 1;59(1):159-64 [9892201] Nucleic Acids Res. 1999 Feb 1;27(3):736-42 [9889267] Cancer Res. 1999 Feb 1;59(3):538-41 [9973196] Mol Cell Biol. 1999 Mar;19(3):2000-7 [10022887] J Biol Chem. 1999 Mar 5;274(10):6336-41 [10037723] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2970-5 [10077621] Mol Cell Biol. 1999 Apr;19(4):3177-83 [10082584] Cancer Res. 1999 Jul 1;59(13):3021-7 [10397236] J Biol Chem. 1999 Nov 5;274(45):32368-75 [10542278] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13914-9 [10570173] Mol Cell Biol. 1997 May;17(5):2859-65 [9111358] Proc Natl Acad Sci U S A. 1997 May 27;94(11):5831-6 [9159160] Genes Dev. 1997 Jun 15;11(12):1573-82 [9203583] Mol Cell Biol. 1997 Aug;17(8):4465-73 [9234704] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10144-9 [9294177] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5 [9618505] Mutat Res. 1998 Mar;407(2):177-87 [9637246] Curr Biol. 1997 Oct 1;7(10):790-3 [9368761] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bullies, Victims, and Bully/Victims:. Distinct Groups of At-Risk Youth AN - 21299534; 11627009 AB - Bullying and victimization are prevalent problems in the area of adolescent peer relationships. Middle school students (N = 4,263) in one Maryland school district completed surveys covering a range of problem behaviors and psychosocial variables. Overall,30.9% of the students reported being victimized three or more times in the past year and 7.4% reported bullying three or more times over the past year. More than one half of the bullies also reported being victimized. Those bully/victims were found to score less favorably than either bullies or victims on all the measured psychosocial and behavioral variables. Results of a discriminant function analysis demonstrated that a group of psychosocial and behavioral predictors-including problem behaviors, attitudes toward deviance, peer influences, depressive symptoms, school-related functioning, and parenting-formed a linear separation between the comparison group (never bullied or victimized), the victim group, the bully group, and the bully/victim group. JF - Journal of Early Adolescence AU - Haynie, Denise L AU - Nansel, Tonja AU - Eitel, Patricia AU - Crump, Aria Davis AU - Saylor, Keith AU - Yu, Kai AU - Simons-Morton, Bruce AD - National Institute of Child Health and Human Development Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 29 EP - 49 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 21 IS - 1 SN - 0272-4316, 0272-4316 KW - Risk Abstracts KW - victimization KW - depression KW - attitudes KW - bullying KW - schools KW - USA, Maryland KW - Adolescents KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21299534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Early+Adolescence&rft.atitle=Bullies%2C+Victims%2C+and+Bully%2FVictims%3A.+Distinct+Groups+of+At-Risk+Youth&rft.au=Haynie%2C+Denise+L%3BNansel%2C+Tonja%3BEitel%2C+Patricia%3BCrump%2C+Aria+Davis%3BSaylor%2C+Keith%3BYu%2C+Kai%3BSimons-Morton%2C+Bruce&rft.aulast=Haynie&rft.aufirst=Denise&rft.date=2001-02-01&rft.volume=21&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+Early+Adolescence&rft.issn=02724316&rft_id=info:doi/10.1177%2F0272431601021001002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-12-15 N1 - SubjectsTermNotLitGenreText - bullying; schools; victimization; depression; Adolescents; attitudes; USA, Maryland DO - http://dx.doi.org/10.1177/0272431601021001002 ER - TY - JOUR T1 - The massively parallel genetic algorithm for RNA folding: MIMD implementation and population variation AN - 18339328; 5148233 AB - A massively parallel Genetic Algorithm (GA) has been applied to RNA sequence folding on three different computer architectures. The GA, an evolution-like algorithm that is applied to a large population of RNA structures based on a pool of helical stems derived from an RNA sequence, evolves this population in parallel. The algorithm was originally designed and developed for a 16384 processor SIMD (Single Instruction Multiple Data) MasPar MP-2. More recently it has been adapted to a 64 processor MIMD (Multiple Instruction Multiple Data) SGI ORIGIN 2000, and a 512 processor MIMD CRAY T3E. The MIMD version of the algorithm raises issues concerning RNA structure data-layout and processor communication. In addition, the effects of population variation on the predicted results are discussed. Also presented are the scaling properties of the algorithm from the perspective of the number of physical processors utilized and the number of virtual processors (RNA structures) operated upon. JF - Bioinformatics AU - Shapiro, BA AU - Wu, Jin Chu AU - Bengali, D AU - Potts, MJ AD - Image Processing Section, Laboratory of Experimental and Computational Biology, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, National Institutes of Health, Bldg 469, Rm 150, Frederick, MD 21702, USA, bshapiro@ncifcrf.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 137 EP - 148 VL - 17 IS - 2 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Computer programs KW - RNA KW - Algorithms KW - Bioinformatics KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18339328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=The+massively+parallel+genetic+algorithm+for+RNA+folding%3A+MIMD+implementation+and+population+variation&rft.au=Shapiro%2C+BA%3BWu%2C+Jin+Chu%3BBengali%2C+D%3BPotts%2C+MJ&rft.aulast=Shapiro&rft.aufirst=BA&rft.date=2001-02-01&rft.volume=17&rft.issue=2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; RNA; Algorithms; Computer programs ER - TY - JOUR T1 - Peer and Parent Influences on Smoking and Drinking Among Early Adolescents AN - 18153944; 4876809 AB - Social influences can promote or discourage adolescent substance use. The authors surveyed 4,263 sixth- to eighth-grade students to assess the effect of peer and parent influences on adolescent substance use. The authors conducted separate multiple logistic regression analyses for smoking and drinking, controlling for grade, sex, and race. Positive independent associations with smoking and drinking were found for direct peer pressure and associating with problem-behaving friends. Independent negative associations with smoking and drinking were also found for parent involvement, parent expectations, and parent regard. In an analysis of interactions, peer pressure was positively associated with drinking for girls but not for boys and problem-behaving friends was positively associated with drinking for both boys and girls. The findings are consistent with the hypothesis that associating with deviant peers promotes and that authoritative parenting protects against smoking and drinking. JF - Health Education & Behavior AU - Simons-Morton, B AU - Haynie, D L AU - Crump, AD AU - Eitel, P AU - Saylor, KE AD - Prevention Research Branch, Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, North Bethesda, MD 20892-7510, USA, Bruce_SimonsMorton@nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 95 EP - 107 VL - 28 IS - 1 SN - 1090-1981, 1090-1981 KW - Physical Education Index KW - Smoking KW - Alcohol KW - Parenting KW - Adolescence KW - Tobacco KW - Parental involvement KW - Health (education) KW - PE 120:Sport: Psychology, Sociology & History UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18153944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Education+%26+Behavior&rft.atitle=Peer+and+Parent+Influences+on+Smoking+and+Drinking+Among+Early+Adolescents&rft.au=Simons-Morton%2C+B%3BHaynie%2C+D+L%3BCrump%2C+AD%3BEitel%2C+P%3BSaylor%2C+KE&rft.aulast=Simons-Morton&rft.aufirst=B&rft.date=2001-02-01&rft.volume=28&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Health+Education+%26+Behavior&rft.issn=10901981&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adolescence; Alcohol; Parental involvement; Parenting; Smoking; Health (education); Tobacco ER - TY - JOUR T1 - Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States) AN - 17901822; 5141450 AB - Objectives: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection. Methods: This multicenter case-control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types. Results: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; greater than or equal to 1 pack per day: OR = 0.7, 95% CI 0.4-1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; greater than or equal to 1 pack per day: OR = 1.8, 95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were similar. Conclusion: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ. JF - Cancer Causes & Control AU - Lacey, JV Jr AU - Frisch, M AU - Brinton, LA AU - Abbas, F M AU - Barnes, WA AU - Gravitt, P E AU - Greenberg, MD AU - Greene, S M AU - Hadjimichael, O C AU - McGowan, L AU - Mortel, R AU - Schwartz, P E AU - Zaino, R J AU - Hildesheim, A AD - Hormonal Studies Section, Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd. MSC 7234, Rockville, MD 20852-7234, USA, laceyj@ex-change.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 153 EP - 161 VL - 12 IS - 2 SN - 0957-5243, 0957-5243 KW - man KW - USA KW - cervix KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts; Virology & AIDS Abstracts KW - Cervical carcinoma KW - Squamous cells KW - Cancer KW - Carcinoma KW - Cigarette smoking KW - Adenocarcinoma KW - Cervix KW - Human papillomavirus KW - R2 23060:Medical and environmental health KW - V 22114:Human oncogenic viruses KW - X 24180:Social poisons & drug abuse KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Associations+between+smoking+and+adenocarcinomas+and+squamous+cell+carcinomas+of+the+uterine+cervix+%28United+States%29&rft.au=Lacey%2C+JV+Jr%3BFrisch%2C+M%3BBrinton%2C+LA%3BAbbas%2C+F+M%3BBarnes%2C+WA%3BGravitt%2C+P+E%3BGreenberg%2C+MD%3BGreene%2C+S+M%3BHadjimichael%2C+O+C%3BMcGowan%2C+L%3BMortel%2C+R%3BSchwartz%2C+P+E%3BZaino%2C+R+J%3BHildesheim%2C+A&rft.aulast=Lacey&rft.aufirst=JV&rft.date=2001-02-01&rft.volume=12&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human papillomavirus; Cigarette smoking; Cancer; Cervix; Carcinoma; Adenocarcinoma; Squamous cells; Cervical carcinoma ER - TY - JOUR T1 - Pharmacological Evaluation of Bangladeshi Medicinal Plants - a Review AN - 17892674; 5124980 AB - The results of pharmacological studies on 64 medicinal plants of Bangladesh have been reviewed. The results encountered in various investigations reveal important pharmacological activities of the plants which may be used as leads in developing novel therapeutic agents. Among the activities tested, the antimicrobial property was the most commonly encountered one. Out of the 64 plants tested, 33 exhibited antibacterial/antifungal activities. Thus, antimicrobial activity was the most commonly observed pharmacological property of the plants included in this review. Among the plants exhibiting antimicrobial properties, Nigella sativa Linn. (Kala jira), Allium sativum Linn. (garlic) and Polyalthia longifolia var. pendulla R. Br. (Debdaru) are the most promising candidates for further studies. Nigella sativa seed and garlic bulb extracts had shown highly potent antibacterial and antifungal activities against multiple drug resistant isolates of Shigella strain. Moreover, positive responses were evident in the in vivo experimental shigellosis in primate models. JF - Pharmaceutical Biology AU - Rahman, S AU - Hasnat, A AU - Hasan, C M AU - Rashid, MA AU - Ilias, M AD - NCI-FCRDC: Bldg. 560, Rm. 32-63B, P.O. Box B, Frederick, MD 21702, USA, rashid@mail.ncifcrf.gov. Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 1 EP - 6 VL - 39 IS - 1 SN - 1388-0209, 1388-0209 KW - pharmacology KW - Bangladesh KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Antifungal agents KW - Shigellosis KW - Reviews KW - Medicinal plants KW - Drug sensitivity testing KW - Herbal medicines KW - Shigella KW - Antibacterial agents KW - Nigella sativa KW - Antimicrobial agents KW - A 01069:Antimicrobial & microbiocidal KW - A 01066:Antibacterial & bactericidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17892674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmaceutical+Biology&rft.atitle=Pharmacological+Evaluation+of+Bangladeshi+Medicinal+Plants+-+a+Review&rft.au=Rahman%2C+S%3BHasnat%2C+A%3BHasan%2C+C+M%3BRashid%2C+MA%3BIlias%2C+M&rft.aulast=Rahman&rft.aufirst=S&rft.date=2001-02-01&rft.volume=39&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Pharmaceutical+Biology&rft.issn=13880209&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella; Nigella sativa; Antibacterial agents; Antifungal agents; Medicinal plants; Reviews; Herbal medicines; Antimicrobial agents; Drug sensitivity testing; Shigellosis ER - TY - JOUR T1 - Isolation of a circular plasmid region sufficient for autonomous replication and transformation of infectious Borrelia burgdorferi AN - 17878330; 5120989 AB - Borrelia burgdorferi contains abundant circular and linear plasmids, but the mechanism of replication of these extrachromosomal elements is unknown. A B. burgdorferi 9 kb circular plasmid (cp9) was amplified in its entirety by the polymerase chain reaction and used to construct a shuttle vector that replicates in Escherichia coli and B. burgdorferi. A 3.3 kb region of cp9 containing three open reading frames was used to construct a smaller shuttle vector, designated pBSV2. This vector was stably maintained in B. burgdorferi, indicating that all elements necessary for autonomous replication are probably located on this 3.3 kb fragment. A non-infectious B. burgdorferi strain was efficiently transformed by pBSV2. Additionally, infectious B. burgdorferi was also successfully transformed by pBSV2, indicating that infectious strains of this important human pathogen can now be genetically manipulated. JF - Molecular Microbiology AU - Stewart, E P AU - Thalken, R AU - Bono, L J AU - Rosa, P AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, USA. Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 714 EP - 721 PB - Blackwell Science Ltd VL - 39 IS - 3 SN - 0950-382X, 0950-382X KW - shuttle vectors KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Transformation KW - Replication KW - Borrelia burgdorferi KW - Plasmids KW - Lyme disease KW - J 02855:Human Bacteriology: Others KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17878330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Isolation+of+a+circular+plasmid+region+sufficient+for+autonomous+replication+and+transformation+of+infectious+Borrelia+burgdorferi&rft.au=Stewart%2C+E+P%3BThalken%2C+R%3BBono%2C+L+J%3BRosa%2C+P&rft.aulast=Stewart&rft.aufirst=E&rft.date=2001-02-01&rft.volume=39&rft.issue=3&rft.spage=714&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Lyme disease; Transformation; Replication; Plasmids ER - TY - JOUR T1 - Genetic Events Associated With Arsenic-Induced Malignant Transformation: Applications of cDNA Microarray Technology AN - 17857892; 4881912 AB - Arsenic is a human carcinogen. Our recent work showed that chronic (> 18 wk), low-level (125-500 nM) arsenite exposure induces malignant transformation in normal rat liver cell line TRL1215. In these arsenic-transformed cells, the cellular S-adenosylmethionine pool was depleted from arsenic metabolism, resulting in global DNA hypomethylation. DNA methylation status in turn may affect the expression of a variety of genes. This study examined the aberrant gene expression associated with arsenic-induced transformation with the use of Atlas Rat cDNA Expression microarrays. Poly(A super(+)) RNA was prepared from arsenic-transformed cells and passage-matched control cells, and super(32)P-labeled cDNA probes were synthesized with Clontech Rat cDNA Synthesis primers and moloney murine leukemia virus reverse transcriptase. The hybrid intensity was analyzed with AtlasImage software and normalized with the sum of the four housekeeping genes. Four hybridizations from separate cell preparations were performed, and mean and SEM for the expression of each gene were calculated for statistical analysis. Among the 588 genes, approximately 80 genes ( similar to 13%) were aberrantly expressed. These included genes involved in cell-cycle regulation, signal transduction, stress response, apoptosis, cytokine production and growth-factor and hormone-receptor production and various oncogenes. These initial gene expression analyses for the first time showed potentially important aberrant gene expression patterns associated with arsenic-induced malignant transformation and set the stage for numerous further studies. JF - Molecular Carcinogenesis AU - Chen, H AU - Liu, J AU - Merrick, BA AU - Waalkes, M P AD - NIEHS, Mail Drop FO-09, 111 Alexander Drive, Research Triangle Park, NC 27709, USA Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 79 EP - 87 VL - 30 IS - 2 SN - 0899-1987, 0899-1987 KW - cDNA Microarray Technology KW - rats KW - cell lines KW - Toxicology Abstracts; Genetics Abstracts KW - Transformation KW - Arsenic KW - Genes KW - Carcinogenesis KW - Liver KW - DNA methylation KW - X 24165:Biochemistry KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17857892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Genetic+Events+Associated+With+Arsenic-Induced+Malignant+Transformation%3A+Applications+of+cDNA+Microarray+Technology&rft.au=Chen%2C+H%3BLiu%2C+J%3BMerrick%2C+BA%3BWaalkes%2C+M+P&rft.aulast=Chen&rft.aufirst=H&rft.date=2001-02-01&rft.volume=30&rft.issue=2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; DNA methylation; Carcinogenesis; Transformation; Genes; Liver ER - TY - JOUR T1 - Impaired development of HIV-1 gp160-specific CD8 super(+) cytotoxic T cells by a delayed switch from Th1 to Th2 cytokine phenotype in mice with Helicobacter pylori infection AN - 17852895; 4874925 AB - Th1 and Th2 cells play a central role in immunoregulation during infection. We show that Helicobacter pylori induces Th1 cytokine responses early (2 weeks) but predominantly Th2 responses later (6 weeks) in infection. The switch is principally mediated by urease-specific CD4 super(+) T cells, and correlates with a loss of urease-specific high-avidity JNK super(+) Th1 and gain of low-avidity JNK super(-) (possibly Th2) cells at the later stage of infection, concomitant with a 100-fold higher colonization level of H. pylori at 6 weeks than at 2 weeks that might tolerize high-avidity Th1 cells. Furthermore, differentiation of HIV gp160-specific CD4 super(+) Th and CD8 super(+) cytotoxic T lymphocytes (CTL) into effector cells is impaired in 6-week H. pylori-infected mice immunized with vaccinia expressing gp160, and serum IL-12 stimulated by vaccinia infection is barely detectable. Adoptive transfer of urease-specific Th2 cells to mice infected only with gp 160-expressing vaccinia abrogates Th1 polarization of the gp120 response, down-modulates virus-specific CTL responses, and delays virus clearance. Therefore, the H. pylori urease-mediated immunoregulation in the switch from JNK super(+) Th1 to JNK super(-) Th2 phenotype, and the preceding low IL-12 response, are likely critical steps in the impairment of antiviral immunity. JF - European Journal of Immunology AU - Shirai, Mutsunori AU - Fujinaga, Ryutaro AU - Masaki, Tsutomu AU - Berzofsky, JA AD - Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Building 10, Room 6B-12, NIH, Bethesda, MD 20892, USA, berzofsk@helix.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 516 EP - 526 VL - 31 IS - 2 SN - 0014-2980, 0014-2980 KW - mice KW - infection KW - antiviral activity KW - HIV KW - CD4 antigen KW - CD8 antigen KW - Helicobacter pylori KW - glycoprotein gp160 KW - Immunology Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - Acquired immune deficiency syndrome KW - Helper cells KW - Immunity KW - Interleukin 12 KW - Human immunodeficiency virus KW - Lymphocytes T KW - Cytokines KW - Immune response KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - F 06756:Function KW - V 22003:AIDS: Immunological aspects KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17852895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Immunology&rft.atitle=Impaired+development+of+HIV-1+gp160-specific+CD8+super%28%2B%29+cytotoxic+T+cells+by+a+delayed+switch+from+Th1+to+Th2+cytokine+phenotype+in+mice+with+Helicobacter+pylori+infection&rft.au=Shirai%2C+Mutsunori%3BFujinaga%2C+Ryutaro%3BMasaki%2C+Tsutomu%3BBerzofsky%2C+JA&rft.aulast=Shirai&rft.aufirst=Mutsunori&rft.date=2001-02-01&rft.volume=31&rft.issue=2&rft.spage=516&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Immunology&rft.issn=00142980&rft_id=info:doi/10.1002%2F1521-4141%28200102%2931%3A23.0.CO%3B2-L LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Human immunodeficiency virus; Acquired immune deficiency syndrome; Lymphocytes T; Cytokines; Interleukin 12; Immunity; Immune response; Helper cells DO - http://dx.doi.org/10.1002/1521-4141(200102)31:2<516::AID-IMMU516>3.0.CO;2-L ER - TY - JOUR T1 - A mixture model for the probability distribution of rain rate AN - 17851105; 4873268 AB - In this paper we present a logistic mixture model for rain rate, that is, a model where the regime probabilities are allowed to change over time and are modeled with a logistic regression structure. Such a model may be used as an alternative to simple mixture, threshold, or hidden Markov models. The maximum likelihood estimates for the model parameters are found using an EM algorithm and their asymptotic properties are stated. The model is fit to hourly measurements of rain rate that are part of the GATE dataset. The results are compared with results from a standard mixture model and from a single density model. JF - Environmetrics AU - Jeffries, N AU - Pfeiffer, R AD - National Cancer Institute, 6120 Executive Blvd/EPS 8017, Rockville, MD 20852, USA, pfeiffer@mail.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 1 EP - 10 VL - 12 IS - 1 SN - 1180-4009, 1180-4009 KW - Aqualine Abstracts; Water Resources Abstracts KW - Rainfall Rate KW - Precipitation (Atmospheric) KW - Distribution KW - Algorithms KW - Precipitation KW - Environmental management KW - Modelling (Stochastic) KW - Model Studies KW - Mathematical analysis KW - AQ 00001:Water Resources and Supplies KW - SW 0815:Precipitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17851105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmetrics&rft.atitle=A+mixture+model+for+the+probability+distribution+of+rain+rate&rft.au=Jeffries%2C+N%3BPfeiffer%2C+R&rft.aulast=Jeffries&rft.aufirst=N&rft.date=2001-02-01&rft.volume=12&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Environmetrics&rft.issn=11804009&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Precipitation (Atmospheric); Environmental management; Modelling (Stochastic); Mathematical analysis; Rainfall Rate; Distribution; Algorithms; Precipitation; Model Studies ER - TY - JOUR T1 - Cationic liposome-mediated gene transfer to rat salivary epithelial cells in vitro and in vivo AN - 17837987; 4872308 AB - Previously we have shown that gene transfer to salivary gland epithelial cells readily occurs via recombinant adenoviruses, although the response is short-lived and results in a potent host immune response. The aim of the present study was to assess the feasibility of using cationic liposomes to mediate gene transfer to rat salivary cells in vitro and in vivo. Initially, for transfection in vitro, we used two cationic liposome formulations (GAP-DLRIE/DOPE and DOSPA/DOPE) complexed with plasmid encoding human growth hormone (hGH) as a reporter gene. Thereafter, using GAP-DLRIE/DOPE, plasmids were transferred to rat salivary glands in vivo, and hGH levels measured in saliva, serum and gland extracts. Under optimal conditions, transfection of rat submandibular glands (SMGs) was consistently observed. Approximately 95% of the cells transfected with a plasmid encoding beta -galactosidase were acinar cells. Maximal hGH expression was obtained during the first 48 h post-transfection using a plasmid encoding the hGH cDNA and complexed with GAP-DLRIE/DOPE. hGH was detected in gland extracts and saliva, and occasionally in serum. No systemic or local gland pathology was consistently or significantly observed. The levels of the reporter gene product, hGH, obtained after GAP-DLRIE/DOPE-mediated gene transfer are considerably lower ( <0.5%) than those achieved with adenoviral vectors (10 super(8) PFU). Nonetheless, cationic liposome-mediated gene transfer to salivary glands may be useful for potential therapeutic applications. JF - Journal of Gene Medicine AU - Baccaglini, L AU - Hoque, ATMS AU - Wellner, R B AU - Goldsmith, C M AU - Redman, R S AU - Sankar, V AU - Kingman, A AU - Barnhart, K M AU - Wheeler, C J AU - Baum, B J AD - GTTB/NIDCR/NIH, Bldg 10, 1N113, MSC-1190, Bethesda, MD 20892-1190, USA, Bruce_J_Baum@nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 82 EP - 90 VL - 3 IS - 1 SN - 1099-498X, 1099-498X KW - rats KW - submandibular glands KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Growth hormone KW - Gene therapy KW - Gene transfer KW - Salivary gland KW - Liposomes KW - W3 33181:Gene therapy vectors KW - G 07401:Rodentia (rats) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17837987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Gene+Medicine&rft.atitle=Cationic+liposome-mediated+gene+transfer+to+rat+salivary+epithelial+cells+in+vitro+and+in+vivo&rft.au=Baccaglini%2C+L%3BHoque%2C+ATMS%3BWellner%2C+R+B%3BGoldsmith%2C+C+M%3BRedman%2C+R+S%3BSankar%2C+V%3BKingman%2C+A%3BBarnhart%2C+K+M%3BWheeler%2C+C+J%3BBaum%2C+B+J&rft.aulast=Baccaglini&rft.aufirst=L&rft.date=2001-02-01&rft.volume=3&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Journal+of+Gene+Medicine&rft.issn=1099498X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Gene therapy; Liposomes; Growth hormone; Salivary gland ER - TY - JOUR T1 - Identification of Rgg-regulated exoproteins of Streptococcus pyogenes AN - 17826350; 4863673 AB - Streptococcus pyogenes secretes many proteins that influence host-pathogen interactions. Despite their importance, relatively little is known about the regulation of these proteins. The rgg gene (also known as ropB) is required for the expression of streptococcal erythrogenic toxin B (SPE B), an extracellular cysteine protease that contributes to virulence. Proteomics was used to determine if rgg regulates the expression of additional exoproteins. Exponential- and stationary-phase culture supernatant proteins made by S. pyogenes NZ131 rgg and NZ131 speB were separated by two-dimensional electrophoresis. Differences were identified in supernatant proteins from both exponential- and stationary-phase cultures, although considerably more differences were detected among stationary-phase supernatant proteins. Forty-two proteins were identified by peptide fingerprinting with matrix-assisted laser desorption mass spectrometry. Mitogenic factor, DNA entry nuclease (open reading frame [ORF 226]), and ORF 953, which has no known function, were more abundant in the culture supernatants of the rgg mutant compared to the speB mutant. ClpB, lysozyme, and autolysin were detected in the culture supernatant of the speB mutant but not the rgg mutant. To determine if Rgg affected protein expression at the transcriptional level, real-time (TaqMan) reverse transcription (RT)-PCR was used to quantitate Rgg-regulated transcripts from NZ131 wild-type and speB and rgg mutant strains. The results obtained with RT-PCR correlated with the proteomic data. We conclude that Rgg regulates the transcription of several genes expressed primarily during the stationary phase of growth. JF - Infection and Immunity AU - Chaussee AU - Watson, RO AU - Smoot, J C AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South Fourth St., Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 822 EP - 831 VL - 69 IS - 2 SN - 0019-9567, 0019-9567 KW - ClpB protein KW - Rgg protein KW - SpeB gene KW - rgg gene KW - Microbiology Abstracts B: Bacteriology KW - Gene expression KW - Virulence KW - Autolysins KW - Lysozyme KW - Gene regulation KW - Polymerase chain reaction KW - Transcripts KW - Streptococcus pyogenes KW - Reverse transcription KW - Mutants KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17826350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Identification+of+Rgg-regulated+exoproteins+of+Streptococcus+pyogenes&rft.au=Chaussee%3BWatson%2C+RO%3BSmoot%2C+J+C%3BMusser%2C+J+M&rft.aulast=Chaussee&rft.aufirst=&rft.date=2001-02-01&rft.volume=69&rft.issue=2&rft.spage=822&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Virulence; Gene expression; Gene regulation; Mutants; Transcripts; Reverse transcription; Polymerase chain reaction; Lysozyme; Autolysins ER - TY - JOUR T1 - Induction of Tumor-Reactive Cytotoxic T-Lymphocytes Using a Peptide from NY-ESO-1 Modified at the Carboxy-terminus to Enhance HLA-A2.1 Binding Affinity and Stability in Solution AN - 17821692; 4857213 AB - NY-ESO-1 is an attractive candidate tumor antigen for the development of immunotherapies for a wide variety of cancers. It is expressed in multiple types of tumors, but its normal tissue distribution is predominantly limited to the testes and ovaries; furthermore, both humoral and cellular immune responses can be mounted against this protein. Three overlapping HLA-A2.1-restricted T-cell epitopes have been identified within NY-ESO-1. In this investigation, the authors evaluated the in vitro immunogenicity of these peptides. From 2 of 12 HLA-A2.1 super(+) patients with metastatic melanoma, peptide-reactive cytotoxic T-lymphocytes were generated using either NY-ESO-1:157-167 or NY-ESO-1:157-165 but not NY-ESO-1:155-163. Because NY-ESO-1:157-165 is a 9 amino acid peptide completely contained within NY-ESO-1:157-167, it seemed likely that this peptide was the minimal determinant, and thus it was selected for continued study. An amino acid substitution of C to V was introduced into NY-ESO-1:157-165 at P9 to attempt to improve its immunogenicity by enhancing its binding affinity to HLA-A2.1 and increasing its stability in solution, because the C residue is readily oxidized, leading to dimerization of the peptide. From 5 of 20 HLA-A2.1 super(+) patients with metastatic melanoma, NY-ESO-1:157-165(165V) stimulated cytotoxic T-lymphocytes in vitro, which recognized peptide-pulsed target cells and HLA-A2.1 super(+) NY-ESO-1 super(+) tumor cells, suggesting that this peptide may be clinically valuable for the treatment of patients with NY-ESO-1 super(+) tumors. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - Bownds, S AU - Tong-On, P AU - Rosenberg, SA AU - Parkhurst, M AD - NIH/NCI Surgery Branch Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892-1502, USA, Maria_Parkhurst@nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 1 EP - 9 VL - 24 IS - 1 SN - 1053-8550, 1053-8550 KW - man KW - A2 determinant KW - histocompatibility antigen HLA KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Immunotherapy KW - Cancer patients KW - Lymphocytes T KW - Tumors KW - Killer cells KW - F 06818:Cancer immunotherapy KW - F 06824:Animal KW - F 06756:Function KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17821692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.atitle=Induction+of+Tumor-Reactive+Cytotoxic+T-Lymphocytes+Using+a+Peptide+from+NY-ESO-1+Modified+at+the+Carboxy-terminus+to+Enhance+HLA-A2.1+Binding+Affinity+and+Stability+in+Solution&rft.au=Bownds%2C+S%3BTong-On%2C+P%3BRosenberg%2C+SA%3BParkhurst%2C+M&rft.aulast=Bownds&rft.aufirst=S&rft.date=2001-02-01&rft.volume=24&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lymphocytes T; Killer cells; Tumors; Immunotherapy; Cancer patients ER - TY - JOUR T1 - Toward a genome-scale understanding of group A Streptococcus pathogenesis AN - 17818434; 4856276 AB - Recent significant contributions have been made to the understanding of Group A Streptococcus (GAS) pathogenesis. New regulatory pathways have been discovered, insight into the molecular basis of epidemics of serotype M1 disease has been obtained, the crystal structures of four toxins have been reported and a genome sequence of one GAS strain has been determined. Genome-scale approaches to the study of GAS pathogenesis are now rapidly emerging and will advance our fundamental understanding of the molecular basis of host-pathogen interactions. JF - Current Opinion in Microbiology AU - Graham, M R AU - Smoot, L M AU - Lei, B F AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 65 EP - 70 VL - 4 IS - 1 SN - 1369-5274, 1369-5274 KW - pathogenesis KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Genes KW - Reviews KW - Crystal structure KW - Toxins KW - Streptococcus pyogenes KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17818434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Microbiology&rft.atitle=Toward+a+genome-scale+understanding+of+group+A+Streptococcus+pathogenesis&rft.au=Graham%2C+M+R%3BSmoot%2C+L+M%3BLei%2C+B+F%3BMusser%2C+J+M&rft.aulast=Graham&rft.aufirst=M&rft.date=2001-02-01&rft.volume=4&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Crystal structure; Toxins; Genomes; Genes; Reviews ER - TY - JOUR T1 - Prediction of the Archaeal Exosome and Its Connections with the Proteasome and the Translation and Transcription Machineries by a Comparative-Genomic Approach AN - 17809928; 4854668 AB - By comparing the gene order in the completely sequenced archaeal genomes complemented by sequence profile analysis, we predict the existence and protein composition of the archaeal counterpart of the eukaryotic exosome, a complex of RNAses, RNA-binding proteins, and helicases that mediates processing and 3'->5' degradation of a variety of RNA species. The majority of the predicted archaeal exosome subunits are encoded in what appears to be a previously undetected superoperon. In Methanobacterium thermoautotrophicum, this predicted superoperon consists of 15 genes; in the Crenarchaea, Sulfolobus solfotaricus and Aeropyrum pernix, one and two of the genes from the superoperon, respectively, are relocated in the genome, whereas in other Euryarchaeota, the superoperon is split into a variable number of predicted operons and solitary genes. Methanococcus jannaschii partially retains the superoperon, but lacks the three core exosome subunits, and in Halobacterium sp., the superoperon is divided into two predicted operons, with the same three exosome subunits missing. This suggests concerted gene loss and an alteration of the structure and function of the predicted exosome in the Methanococcus and Halobacterium lineages. Additional potential components of the exosome are encoded by partially conserved predicted small operons. Along with the orthologs of eukaryotic exosome subunits, namely an RNase PH and two RNA-binding proteins, the predicted archaeal exosomal superoperon also encodes orthologs of two protein subunits of RNase P. This suggests a functional and possibly a physical interaction between RNase P and the postulated archaeal exosome, a connection that has not been reported in eukaryotes. In a pattern of apparent gene loss complementary to that seen in Methanococcus and Halobacterium, Thermoplasma acidophilum lacks the RNase P subunits. Unexpectedly, the identified exosomal superoperon, in addition to the predicted exosome components, encodes the catalytic subunits of the archaeal proteasome, two ribosomal proteins and a DNA-directed RNA polymerase subunit. These observations suggest that in archaea, a tight functional coupling exists between translation, RNA processing and degradation, (apparently mediated by the predicted exosome) and protein degradation (mediated by the proteasome), and may have implications for cross-talk between these processes in eukaryotes. JF - Genome Research AU - Koonin, E V AU - Wolf, YI AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 240 EP - 252 VL - 11 IS - 2 SN - 1054-9803, 1054-9803 KW - exosome KW - ribonuclease H KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Archaea KW - Methanococcus jannaschii KW - Transcription KW - Ribonuclease P KW - Halobacterium KW - Euryarchaeota KW - Multicatalytic endopeptidase complex KW - Sulfolobus solfotaricus KW - DNA-directed RNA polymerase KW - Protein biosynthesis KW - RNA-binding protein KW - Thermoplasma acidophilum KW - Crenarchaea KW - Aeropyrum pernix KW - Methanobacterium thermoautotrophicum KW - Gene regulation KW - G 07320:Bacterial genetics KW - N 14555:Miscellaneous KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17809928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+Research&rft.atitle=Prediction+of+the+Archaeal+Exosome+and+Its+Connections+with+the+Proteasome+and+the+Translation+and+Transcription+Machineries+by+a+Comparative-Genomic+Approach&rft.au=Koonin%2C+E+V%3BWolf%2C+YI%3BAravind%2C+L&rft.aulast=Koonin&rft.aufirst=E&rft.date=2001-02-01&rft.volume=11&rft.issue=2&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10549803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Archaea; Methanobacterium thermoautotrophicum; Crenarchaea; Sulfolobus solfotaricus; Aeropyrum pernix; Euryarchaeota; Methanococcus jannaschii; Halobacterium; Thermoplasma acidophilum; Multicatalytic endopeptidase complex; Protein biosynthesis; Transcription; Gene regulation; RNA-binding protein; Ribonuclease P; DNA-directed RNA polymerase ER - TY - JOUR T1 - A quantification of human cells using an ERV-3 real time PCR assay AN - 17777299; 4829824 AB - A novel approach to quantifying human cells using a real time PCR assay was developed. The target sequence used in the assay is a 135 bp segment within the unique 1.7 kb Hind III / Pst I fragment of the ERV-3 envelope gene. ERV-3 is a full-length human endogenous retrovirus present in known copy number in all human cells. The detection range of ERV-3 by real time PCR is from 10 super(6) to 10 super(1). The precision described, sensitivity and specificity of the assay indicate that the ERV-3 sequence is an accurate cell quantitation marker. The quantitative ERV-3 assay enables simple, fast, and reproducible detection and quantitation of the cell number. The assay can be used to determine the sample DNA conditions and also it can be used to adjust the quantitative DNA measurements of other target gene assays relative to the number of cell equivelants. JF - Journal of Virological Methods AU - Chin Yuan, C AU - Miley, W AU - Waters, D AD - Virus Epidemiology Section, AIDS Vaccine Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, 21702 Frederick, MD USA Y1 - 2001/02/01/ PY - 2001 DA - 2001 Feb 01 SP - 109 EP - 117 PB - Elsevier VL - 91 IS - 2 SN - 0166-0934, 0166-0934 KW - man KW - quantification KW - ERV-3 gene KW - ERV3 gene KW - Retrovirus KW - human cells KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Envelopes KW - Cell number KW - Measuring techniques KW - DNA KW - Polymerase chain reaction KW - W3 33243:Molecular methods KW - V 22022:Virus assay KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17777299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virological+Methods&rft.atitle=A+quantification+of+human+cells+using+an+ERV-3+real+time+PCR+assay&rft.au=Chin+Yuan%2C+C%3BMiley%2C+W%3BWaters%2C+D&rft.aulast=Chin+Yuan&rft.aufirst=C&rft.date=2001-02-01&rft.volume=91&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virological+Methods&rft.issn=01660934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Retrovirus; Cell number; Envelopes; Measuring techniques; Polymerase chain reaction; DNA ER - TY - JOUR T1 - Human immunodeficiency virus type 2 lentiviral vectors: packaging signal and splice donor in expression and encapsidation AN - 17753340; 4813030 AB - Retroviral vectors provide the means for gene transfer with long-term expression. The lentivirus subgroup of retroviruses, such as human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), possesses a number of regulatory and accessory genes and other special elements. These features can be exploited to design vectors for transducing non-dividing as well as dividing cells with the potential for regulated transgene expression. Encapsidation of the transgene RNA in lentiviral vectors is determined by the leader sequence-based multipartite packaging signal. Embedded in the packaging signal is a major splice donor site that, this study shows, is not by itself essential for transgene expression or encapsidation. We designed HIV-2 vectors that contained all the sequence elements thought to be necessary and sufficient for vector RNA encapsidation. Unexpectedly, despite abundant expression, only a small fraction of the transgene RNA was encapsidated and the titre of the vector was low. Redesign of the vector with a mutant splice donor resulted in increased vector RNA encapsidation and yielded vectors with high titre. Inefficient encapsidation by the conventionally designed vector was not due to suboptimal Rev responsive element (RRE)-Rev function. Varying the length of RRE in the vector did not change vector RNA encapsidation, nor did the introduction of a synthetic intron into the mutant vector. The vector RNA with the intact splice donor may have been excessively spliced, decreasing the amount of packageable RNA. A titre of 10 super(5) transducing units (TU)/ml was readily obtained for vectors with the neo or GFP transgene, and the vector could be concentrated to a titre of 1- 5x10 super(7) TU/ml. JF - Journal of General Virology AU - D'Costa, J AU - Brown, H M AU - Kundra, P AU - Davis-Warren, A AU - Arya, S K AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, Building 37, Room 5E10, National Institutes of Health, Bethesda, MD 20892, USA, aryas@dc37a.nci.nih.gov Y1 - 2001/02// PY - 2001 DA - Feb 2001 SP - 425 EP - 434 VL - 82 IS - 2 SN - 0022-1317, 0022-1317 KW - HIV-1 KW - HIV-2 KW - Rev responsive element KW - Human immunodeficiency virus 1 KW - Human immunodeficiency virus 2 KW - gfp gene KW - neo gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Splicing KW - Retrovirus KW - Lentivirus KW - Capsid protein KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - V 22045:Assembly, maturation & release KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17753340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+General+Virology&rft.atitle=Human+immunodeficiency+virus+type+2+lentiviral+vectors%3A+packaging+signal+and+splice+donor+in+expression+and+encapsidation&rft.au=D%27Costa%2C+J%3BBrown%2C+H+M%3BKundra%2C+P%3BDavis-Warren%2C+A%3BArya%2C+S+K&rft.aulast=D%27Costa&rft.aufirst=J&rft.date=2001-02-01&rft.volume=82&rft.issue=2&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Journal+of+General+Virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Author for correspondence: Suresh Arya. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Lentivirus; Human immunodeficiency virus 2; Capsid protein; Acquired immune deficiency syndrome; Retrovirus; Splicing ER - TY - JOUR T1 - Apoptosis of PC12 cells by 4-hydroxy-2-nonenal is mediated through selective activation of the c-Jun N-terminal protein kinase pathway. AN - 77066427; 11306108 AB - Cytotoxic lipid peroxides such as 4-hydroxy-2-nonenal (HNE) are produced when cells are exposed to toxic chemicals. However, the mechanism by which HNE induces cell death has been poorly understood. In this study, we investigated the molecular mechanism of HNE-induced apoptosis in PC12 cells by measuring the activities of the mitogen-activated protein (MAP) kinases involved in early signal transduction pathways. Within 15-30 min after HNE treatment, c-Jun N-terminal protein kinase (JNK) was maximally activated, before returning to control level after 1 h post-treatment. In contrast, activities of extracellular signal regulated kinase (ERK) and p38 MAP kinase remained unchanged from their basal levels. SEK1, an upstream kinase of JNK, was also activated (phosphorylated) within 5 min after HNE treatment and remained activated for up to 60 min. Marked activation of the JNK pathway through SEK1 was demonstrated by the transient transfection of cDNA for wild type SEK1 and JNK into COS-7 cells. Furthermore, significant reductions in JNK activation and HNE-induced cell death were observed when the dominant negative mutant of SEK1 was co-transfected with JNK. Pretreatment of PC12 cells with a survival promoting agent, 8-(4-chlorophenylthio)-cAMP, prevented both the HNE-induced JNK activation and apoptosis. Nonaldehyde, a nontoxic aldehyde, caused neither apoptosis nor JNK activation. Pretreatment of PC12 cells with SB203580, a specific inhibitor of p38 MAP kinase, had no effect on HNE-induced apoptosis. All these data suggest that the HNE-mediated apoptosis of PC12 cells is likely to be mediated through the selective activation of the SEK1-JNK pathway without activation of ERK or p38 MAP kinase. JF - Chemico-biological interactions AU - Song, B J AU - Soh, Y AU - Bae, M AU - Pie, J AU - Wan, J AU - Jeong, K AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 12420 Parklawn Drive, 20852, Rockville, MD, USA. bjs@mail.nih.gvo Y1 - 2001/01/30/ PY - 2001 DA - 2001 Jan 30 SP - 943 EP - 954 VL - 130-132 IS - 1-3 SN - 0009-2797, 0009-2797 KW - Aldehydes KW - 0 KW - Enzyme Inhibitors KW - Imidazoles KW - Neuroprotective Agents KW - Pyridines KW - Thionucleotides KW - 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP KW - 41941-66-6 KW - Cyclic AMP KW - E0399OZS9N KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - 4-hydroxy-2-nonenal KW - K1CVM13F96 KW - SB 203580 KW - OU13V1EYWQ KW - Index Medicus KW - Animals KW - Imidazoles -- pharmacology KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Thionucleotides -- pharmacology KW - Phosphorylation KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Pyridines -- pharmacology KW - Signal Transduction KW - PC12 Cells KW - Aldehydes -- toxicity KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Cyclic AMP -- pharmacology KW - Apoptosis -- drug effects KW - Cyclic AMP -- analogs & derivatives KW - Aldehydes -- administration & dosage KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77066427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Apoptosis+of+PC12+cells+by+4-hydroxy-2-nonenal+is+mediated+through+selective+activation+of+the+c-Jun+N-terminal+protein+kinase+pathway.&rft.au=Song%2C+B+J%3BSoh%2C+Y%3BBae%2C+M%3BPie%2C+J%3BWan%2C+J%3BJeong%2C+K&rft.aulast=Song&rft.aufirst=B&rft.date=2001-01-30&rft.volume=130-132&rft.issue=1-3&rft.spage=943&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Failure of ductus arteriosus closure and remodeling in neonatal mice deficient in cyclooxygenase-1 and cyclooxygenase-2. AN - 70637694; 11158594 AB - The transition to pulmonary respiration following birth requires rapid alterations in the structure of the mammalian cardiovascular system. One dramatic change that occurs is the closure and remodeling of the ductus arteriosus (DA), an arterial connection in the fetus that directs blood flow away from the pulmonary circulation. A role for prostaglandins in regulating the closure of this vessel has been supported by pharmacological and genetic studies. The production of prostaglandins is dependent on two cyclooxygenases (COX-1 and COX-2), which are encoded by separate genes. We report here that the absence of either or both COX isoforms in mice does not result in premature closure of the DA in utero. However, 35% of COX-2(-/-) mice die with a patent DA within 48 h of birth. In contrast, the absence of only the COX-1 isoform does not affect closure of the DA. The mortality (35%) and patent DA incidence due to absence of COX-2 is, however, significantly increased (79%) when one copy of the gene encoding COX-1 is also inactivated. Furthermore, 100% of the mice deficient in both isoforms die with a patent DA within 12 h of birth, indicating that in COX-2-deficient mice, the contribution of COX-1 to DA closure is gene dosage-dependent. Together, these data establish roles for COX-1, and especially for COX-2, in the transition of the cardiopulmonary circulation at birth. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Loftin, C D AU - Trivedi, D B AU - Tiano, H F AU - Clark, J A AU - Lee, C A AU - Epstein, J A AU - Morham, S G AU - Breyer, M D AU - Nguyen, M AU - Hawkins, B M AU - Goulet, J L AU - Smithies, O AU - Koller, B H AU - Langenbach, R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, Comparative Medicine Branch, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2001/01/30/ PY - 2001 DA - 2001 Jan 30 SP - 1059 EP - 1064 VL - 98 IS - 3 SN - 0027-8424, 0027-8424 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Index Medicus KW - Animals KW - Death KW - Ductus Arteriosus -- pathology KW - Mice KW - Mice, Knockout KW - Genomic Imprinting KW - Genotype KW - Mice, Inbred Strains KW - Animals, Newborn KW - Mice, Inbred C57BL KW - Time Factors KW - Female KW - Male KW - Prostaglandin-Endoperoxide Synthases -- deficiency KW - Isoenzymes -- deficiency KW - Ductus Arteriosus, Patent -- genetics KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Ductus Arteriosus, Patent -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70637694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Failure+of+ductus+arteriosus+closure+and+remodeling+in+neonatal+mice+deficient+in+cyclooxygenase-1+and+cyclooxygenase-2.&rft.au=Loftin%2C+C+D%3BTrivedi%2C+D+B%3BTiano%2C+H+F%3BClark%2C+J+A%3BLee%2C+C+A%3BEpstein%2C+J+A%3BMorham%2C+S+G%3BBreyer%2C+M+D%3BNguyen%2C+M%3BHawkins%2C+B+M%3BGoulet%2C+J+L%3BSmithies%2C+O%3BKoller%2C+B+H%3BLangenbach%2C+R&rft.aulast=Loftin&rft.aufirst=C&rft.date=2001-01-30&rft.volume=98&rft.issue=3&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Prostaglandins Other Lipid Mediat. 1999 Nov;58(5-6):231-52 [10593166] Circulation. 1999 Oct 19;100(16):1751-6 [10525496] Nat New Biol. 1971 Jun 23;231(25):232-5 [5284360] Pediatr Clin North Am. 1986 Jun;33(3):545-60 [3520463] N Engl J Med. 1988 Aug 11;319(6):327-31 [3393194] Am J Obstet Gynecol. 1990 Feb;162(2):549-54 [2309841] Am J Obstet Gynecol. 1993 May;168(5):1350-3 [8498410] Obstet Gynecol Surv. 1993 Jul;48(7):493-502 [8355924] Cardiovasc Res. 1993 Dec;27(12):2205-11 [8313430] J Pharmacol Exp Ther. 1994 Oct;271(1):390-6 [7965740] J Cardiovasc Pharmacol. 1995 Jan;25(1):113-8 [7723339] Am J Obstet Gynecol. 1995 Jul;173(1):20-5 [7631682] Cell. 1995 Nov 3;83(3):473-82 [8521477] Cell. 1995 Nov 3;83(3):483-92 [8521478] Nature. 1995 Nov 23;378(6555):406-9 [7477380] Adv Immunol. 1996;62:167-215 [8781269] Lancet. 1997 Jul 26;350(9073):265-6 [9242810] Am J Obstet Gynecol. 1997 Aug;177(2):256-9; discussion 259-61 [9290437] Nature. 1997 Nov 6;390(6655):78-81 [9363893] J Soc Gynecol Investig. 1995 May-Jun;2(3):526-30 [9420854] Pharmacol Rev. 1998 Mar;50(1):35-58 [9549757] Biochem Biophys Res Commun. 1998 May 8;246(1):7-12 [9600059] Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11875-9 [9751758] Inflamm Res. 1998 Oct;47 Suppl 2:S78-87 [9831328] Endocrinology. 1999 Jun;140(6):2685-95 [10342859] J Clin Invest. 1999 Sep;104(6):721-32 [10491407] Am J Physiol Regul Integr Comp Physiol. 2000 Jun;278(6):R1415-23 [10848506] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA polymerase iota and related rad30-like enzymes. AN - 70593107; 11205331 AB - Until recently, the molecular mechanisms of translesion DNA synthesis (TLS), a process whereby a damaged base is used as a template for continued replication, was poorly understood. This area of scientific research has, however, been revolutionized by the finding that proteins long implicated in TLS are, in fact, DNA polymerases. Members of this so-called UmuC/DinB/Rev1/Rad30 superfamily of polymerases have been identified in prokaryotes, eukaryotes and archaea. Biochemical studies with the highly purified polymerases reveal that some, but not all, can traverse blocking lesions in template DNA. All of them share a common feature, however, in that they exhibit low fidelity when replicating undamaged DNA. Of particular interest to us is the Rad30 subfamily of polymerases found exclusively in eukaryotes. Humans possess two Rad30 paralogs, Rad30A and Rad30B. The RAD30A gene encodes DNA polymerase eta and defects in the protein lead to the xeroderma pigmentosum variant (XP-V) phenotype in humans. Very recently RAD30B has also been shown to encode a novel DNA polymerase, designated as Pol iota. Based upon in vitro studies, it appears that Pol iota has the lowest fidelity of any eukaryotic polymerase studied to date and we speculate as to the possible cellular functions of such a remarkably error-prone DNA polymerase. JF - Philosophical transactions of the Royal Society of London. Series B, Biological sciences AU - McDonald, J P AU - Tissier, A AU - Frank, E G AU - Iwai, S AU - Hanaoka, F AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, MD 20892-2725, USA. Y1 - 2001/01/29/ PY - 2001 DA - 2001 Jan 29 SP - 53 EP - 60 VL - 356 IS - 1405 SN - 0962-8436, 0962-8436 KW - Bacterial Proteins KW - 0 KW - DinB protein, E coli KW - Escherichia coli Proteins KW - Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - POLK protein, human KW - Rad30 protein KW - Index Medicus KW - Saccharomyces cerevisiae -- physiology KW - Humans KW - Bacterial Proteins -- physiology KW - DNA-Directed DNA Polymerase -- physiology KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70593107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Philosophical+transactions+of+the+Royal+Society+of+London.+Series+B%2C+Biological+sciences&rft.atitle=DNA+polymerase+iota+and+related+rad30-like+enzymes.&rft.au=McDonald%2C+J+P%3BTissier%2C+A%3BFrank%2C+E+G%3BIwai%2C+S%3BHanaoka%2C+F%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=2001-01-29&rft.volume=356&rft.issue=1405&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Philosophical+transactions+of+the+Royal+Society+of+London.+Series+B%2C+Biological+sciences&rft.issn=09628436&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1998 Apr;148(4):1599-610 [9560379] Immunol Rev. 1998 Apr;162:13-24 [9602348] Mol Gen Genet. 1998 Apr;257(6):686-92 [9604893] J Exp Med. 1998 Jun 1;187(11):1735-43 [9607915] Cancer Res. 1998 Jun 1;58(11):2445-8 [9622087] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6953-8 [9618520] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9755-60 [9707548] Trends Biochem Sci. 1998 Oct;23(10):403-5 [9810230] Mol Cell Biol. 1999 Jan;19(1):147-54 [9858539] Science. 1999 Feb 12;283(5404):1001-4 [9974380] Mol Cell Biol. 1999 Mar;19(3):2206-11 [10022907] Mutat Res. 1999 Mar;436(2):157-78 [10095138] Nature. 1982 Nov 18;300(5889):278-81 [6755263] Microbiol Rev. 1984 Mar;48(1):60-93 [6371470] Mol Gen Genet. 1984;196(2):364-6 [6092873] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] J Biol Chem. 1999 Nov 5;274(45):31763-6 [10542196] Genes Cells. 1999 Nov;4(11):607-18 [10620008] Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):565-70 [10639119] J Biol Chem. 2000 Mar 17;275(11):7447-50 [10713043] J Biol Chem. 2000 Mar 17;275(11):8233-9 [10713149] Science. 2000 Mar 24;287(5461):2185-95 [10731132] Trends Biochem Sci. 2000 Apr;25(4):189-95 [10754553] Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3838-43 [10760255] Biochemistry. 2000 Apr 25;39(16):4575-80 [10769112] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4331-5 [2989816] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4336-40 [2989817] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3904-8 [2940594] J Bacteriol. 1989 Jan;171(1):230-7 [2492497] Mol Gen Genet. 1989 Aug;218(2):323-9 [2674658] J Bacteriol. 1990 Sep;172(9):4964-78 [2144275] J Bacteriol. 1990 Sep;172(9):4979-87 [2203737] Nucleic Acids Res. 1990 Sep 11;18(17):5045-50 [2129552] J Bacteriol. 1991 Sep;173(18):5604-11 [1885540] Mol Gen Genet. 1991 Sep;229(1):27-30 [1680217] Mol Cell Biol. 1993 Jul;13(7):4276-83 [8321229] Nature. 1995 Jul 20;376(6537):225-9 [7617031] Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):11975-9 [8618826] J Immunol. 1996 Apr 1;156(7):2642-52 [8786330] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2941-6 [8610147] J Biol Chem. 1996 May 3;271(18):10767-74 [8631887] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7805-10 [8755557] Mutat Res. 1996 Oct 25;357(1-2):245-53 [8876701] Comput Appl Biosci. 1996 Aug;12(4):357-8 [8902363] Cancer Surv. 1996;28:117-40 [8977032] J Bacteriol. 1997 Sep;179(18):5693-8 [9294423] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13792-7 [9391106] Genetics. 1997 Dec;147(4):1557-68 [9409821] Int Immunol. 1999 May;11(5):825-33 [10330287] J Pathol. 1999 Jan;187(2):158-63 [10365090] EMBO J. 1999 Jun 15;18(12):3491-501 [10369688] Nature. 1999 Jun 17;399(6737):700-4 [10385124] Science. 1999 Jul 9;285(5425):263-5 [10398605] J Exp Med. 1999 Jul 5;190(1):21-30 [10429667] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8919-24 [10430871] Genomics. 1999 Aug 15;60(1):20-30 [10458907] Genes Dev. 1999 Sep 1;13(17):2191-5 [10485842] Mol Cell. 1999 Aug;4(2):281-6 [10488344] Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11922-7 [10518552] Nature. 2000 Apr 27;404(6781):1014-8 [10801133] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5681-3 [10811923] EMBO J. 2000 Jun 15;19(12):3100-9 [10856253] Genes Dev. 2000 Jul 1;14(13):1589-94 [10887153] Genes Dev. 2000 Jul 1;14(13):1642-50 [10887158] EMBO J. 2000 Oct 2;19(19):5259-66 [11013228] J Invest Dermatol. 1973 Jan;60(1):29-32 [4684158] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Mol Gen Genet. 1978 Sep 20;165(1):87-93 [362169] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proofreading of DNA polymerase eta-dependent replication errors. AN - 70861784; 11113111 AB - Human DNA polymerase eta, the product of the skin cancer susceptibility gene XPV, bypasses UV photoproducts in template DNA that block synthesis by other DNA polymerases. Pol eta lacks an intrinsic proofreading exonuclease and copies DNA with low fidelity, such that pol eta errors could contribute to mutagenesis unless they are corrected. Here we provide evidence that pol eta can compete with other human polymerases during replication of duplex DNA, and in so doing it lowers replication fidelity. However, we show that pol eta has low processivity and extends mismatched primer termini less efficiently than matched termini. These properties could provide an opportunity for extrinsic exonuclease(s) to proofread pol eta-induced replication errors. When we tested this hypothesis during replication in human cell extracts, pol eta-induced replication infidelity was found to be modulated by changing the dNTP concentration and to be enhanced by adding dGMP to a replication reaction. Both effects are classical hallmarks of exonucleolytic proofreading. Thus, pol eta is ideally suited for its role in reducing UV-induced mutagenesis and skin cancer risk, in that its relaxed base selectivity may facilitate efficient bypass of UV photoproducts, while subsequent proofreading by extrinsic exonuclease(s) may reduce its mutagenic potential. JF - The Journal of biological chemistry AU - Bebenek, K AU - Matsuda, T AU - Masutani, C AU - Hanaoka, F AU - Kunkel, T A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/01/26/ PY - 2001 DA - 2001 Jan 26 SP - 2317 EP - 2320 VL - 276 IS - 4 SN - 0021-9258, 0021-9258 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Index Medicus KW - DNA Repair KW - Models, Genetic KW - Humans KW - Base Pair Mismatch KW - Exodeoxyribonucleases -- metabolism KW - Mutagenesis KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70861784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Proofreading+of+DNA+polymerase+eta-dependent+replication+errors.&rft.au=Bebenek%2C+K%3BMatsuda%2C+T%3BMasutani%2C+C%3BHanaoka%2C+F%3BKunkel%2C+T+A&rft.aulast=Bebenek&rft.aufirst=K&rft.date=2001-01-26&rft.volume=276&rft.issue=4&rft.spage=2317&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-21 N1 - Date created - 2001-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutants exhibiting enhanced transcriptional activation and altered promoter selectivity are revealed using a sensitive, yeast-based functional assay. AN - 77074254; 11313981 AB - Changes in promoter specificity and binding affinity that may be associated with p53 mutations or post-translational modifications are useful in understanding p53 structure/function relationships and categorizing tumor mutations. We have exploited variable expression of human p53 in yeast to identify mutants with novel phenotypes that would correspond to altered promoter selectivity and affinity. The p53 cDNA regions coding for the DNA binding and tetramerization domains were subjected to random PCR mutagenesis and were cloned directly by recombination in yeast into a vector with a GAL1 promoter whose level of expression could be easily varied. p53 variants exhibiting higher than wild type levels of transactivation (supertrans) for the RGC responsive element were identified at low level of p53 protein expression. All the p53 mutants obtained with this screen were located in the DNA binding domain. Two out of 17 supertrans mutants have been found in tumors. Six mutations were in the L1 loop region between amino acids 115 and 124. The transactivation potential of a panel of supertrans p53 mutants on different promoters was evaluated using the p53 responsive elements, RGC, PIG3, p21 and bax. Although all mutants retained some activity with all promoters, we found different patterns of induction based on strength and promoter specificity. In particular none of the mutants was supertrans for the p21 responsive element. Interestingly, further analysis in yeast showed that the transactivation function could be retained even in the presence of dominant-negative p53 tumor mutations that could inhibit wild type p53. Five mutants were also characterized in human cells in terms of growth suppression and transactivation of various promoters. These novel supertrans p53 mutants may be useful in studies aimed at dissecting p53 downstream pathways, understanding specific interactions between p53 and the DNA, and could replace wild type p53 in cancer gene therapy protocols. The approach may also prove useful in identifying p53 tumor mutations. JF - Oncogene AU - Inga, A AU - Monti, P AU - Fronza, G AU - Darden, T AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences (NIEHS), PO Box 12233, Research Triangle Park, North Carolina, NC 27709, USA. Y1 - 2001/01/25/ PY - 2001 DA - 2001 Jan 25 SP - 501 EP - 513 VL - 20 IS - 4 SN - 0950-9232, 0950-9232 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Alleles KW - Models, Molecular KW - Models, Genetic KW - Humans KW - Response Elements KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Mutation KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77074254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=p53+mutants+exhibiting+enhanced+transcriptional+activation+and+altered+promoter+selectivity+are+revealed+using+a+sensitive%2C+yeast-based+functional+assay.&rft.au=Inga%2C+A%3BMonti%2C+P%3BFronza%2C+G%3BDarden%2C+T%3BResnick%2C+M+A&rft.aulast=Inga&rft.aufirst=A&rft.date=2001-01-25&rft.volume=20&rft.issue=4&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inducible mutagenesis in TEPC 2372, a mouse plasmacytoma cell line that harbors the transgenic shuttle vector lambdaLIZ. AN - 70630788; 11166031 AB - The plasmacytoma cell line, TEPC 2372, was derived from a malignant plasma cell tumor that developed in the peritoneal cavity of a BALB/c mouse that harbored the transgenic shuttle vector for the assessment of mutagenesis in vivo, lambdaLIZ. TEPC 2372 was found to display the typical features of a BALB/c plasmacytoma. It consisted of pleomorphic plasma cells that secreted a monoclonal immunoglobulin (IgG2b/lambda), was initially dependent on the presence of IL-6 to grow in cell culture, contained a hyperdiploid chromosome complement with a tendency to undergo tetraploidization, and harbored a constitutively active c-myc gene by virtue of a T(6;15) chromosomal translocation. TEPC 2372 was further characterized by the ability to respond to in vitro exposure with 4-NQO (4-nitroquinoline-1-oxide), an oxidative model mutagen, with a vigorous dose-dependent increase in mutagenesis that peaked at a 7.85-fold elevation of mutant rates in lambdaLIZ when compared to background mutant rates in untreated controls. Cotreatment with 4-NQO and BSO (buthionine sulfoximine), a glutathione-depleting compound that causes endogenous oxidative stress, resulted in a 9.03-fold increase in the mutant frequency in lambdaLIZ. These results demonstrated that TEPC 2372, the malignant plasma cell counterpart of the lambdaLIZ-based in vivo mutagenesis assay, may be useful as an in vitro reference point for the further elucidation of oxidative mutagenesis in lymphoid tissues. JF - Mutation research AU - Felix, K AU - Kovalchuk, A L AU - Park, S S AU - Coleman, A E AU - Ramsay, E S AU - Qian, M AU - Kelliher, K A AU - Jones, G M AU - Ried, T AU - Bornkamm, G W AU - Janz, S AD - Laboratory of Genetics, DBS, NCI, Building 37, Room 2B10, Bethesda, MD 20892-4255, USA. felixk@dc37a.nci.nih.gov Y1 - 2001/01/25/ PY - 2001 DA - 2001 Jan 25 SP - 121 EP - 136 VL - 473 IS - 1 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - RNA, Messenger KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Animals KW - Mutagenicity Tests KW - Terpenes -- administration & dosage KW - Cytogenetic Analysis KW - Carcinogens -- administration & dosage KW - Tumor Cells, Cultured KW - RNA, Messenger -- analysis KW - Mice, Inbred C57BL KW - Mice KW - Genetic Vectors -- adverse effects KW - Mice, Transgenic KW - Genes, myc -- genetics KW - Translocation, Genetic KW - Mutagenesis -- drug effects KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70630788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Inducible+mutagenesis+in+TEPC+2372%2C+a+mouse+plasmacytoma+cell+line+that+harbors+the+transgenic+shuttle+vector+lambdaLIZ.&rft.au=Felix%2C+K%3BKovalchuk%2C+A+L%3BPark%2C+S+S%3BColeman%2C+A+E%3BRamsay%2C+E+S%3BQian%2C+M%3BKelliher%2C+K+A%3BJones%2C+G+M%3BRied%2C+T%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=2001-01-25&rft.volume=473&rft.issue=1&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomics: implications for toxicology AN - 17781940; 4829860 AB - The primary goal of the Environmental Genome Project (EGP) is the identification of human polymorphisms indicative of susceptibility to specific environmental agents. Despite evidence for a substantial genetic contribution to disease variation in the population, progress towards identifying specific genes has been slow. To date, most of the advances in our understanding of human diseases has come from genetic analyses of monogenic diseases that affect a relatively small portion of the population. The principal strategy of the EGP involves resequencing DNA samples from populations representative of the US racial and ethnic groups to develop a database of variations. Polymorphisms in specific genes may also be detected by gene-expression profiling. The identification of polymorphisms by resequencing is straightforward, and can be accomplished with minimal difficulty. Gene-expression profiling is still problematic; however, determining the functional significance of the allelic variations will be a monumental challenge involving sophisticated proteomics and population-based and animal model studies. These studies will change radically the practice of public health and clinical medicine, and the approach to the development of pharmaceuticals. JF - Mutation Research AU - Olden, K AU - Guthrie, J AD - Department of Health and Human Services, National Institute of Environmental Health Sciences and National Toxicology Program, National Institutes of Health, 27709 Research Triangle Park, NC USA Y1 - 2001/01/25/ PY - 2001 DA - 2001 Jan 25 SP - 3 EP - 10 PB - Elsevier VL - 473 IS - 1 SN - 0027-5107, 0027-5107 KW - polymorphism KW - Environmental Genome Project KW - genomics KW - Genetics Abstracts; Toxicology Abstracts KW - Gene expression KW - Reviews KW - Animal models KW - Toxicology KW - Ethnic groups KW - G 07220:General theory/testing systems KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17781940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Genomics%3A+implications+for+toxicology&rft.au=Olden%2C+K%3BGuthrie%2C+J&rft.aulast=Olden&rft.aufirst=K&rft.date=2001-01-25&rft.volume=473&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; Ethnic groups; Reviews; Toxicology; Animal models ER - TY - JOUR T1 - Transcriptional regulation of the human acid alpha-glucosidase gene. Identification of a repressor element and its transcription factors Hes-1 and YY1. AN - 70651152; 11038350 AB - Acid alpha-glucosidase, the product of a housekeeping gene, is a lysosomal enzyme that degrades glycogen. A deficiency of this enzyme is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenesis type II. We have previously demonstrated that the human acid alpha-glucosidase gene expression is regulated by a silencer within intron 1, which is located in the 5'-untranslated region. In this study, we have used deletion analysis, electrophoretic mobility shift assay, and footprint analysis to further localize the silencer to a 25-base pair element. The repressive effect on the TK promoter was about 50% in both orientations in expression plasmid, and two transcriptional factors were identified with antibodies binding specifically to the element. Mutagenesis and functional analyses of the element demonstrated that the mammalian homologue 1 of Drosophila hairy and Enhancer of split (Hes-1) binding to an E box (CACGCG) and global transcription factor-YY1 binding to its core site function as a transcriptional repressor. Furthermore, the overexpression of Hes-1 significantly enhanced the repressive effect of the silencer element. The data should be helpful in understanding the expression and regulation of the human acid alpha-glucosidase gene as well as other lysosomal enzyme genes. JF - The Journal of biological chemistry AU - Yan, B AU - Heus, J AU - Lu, N AU - Nichols, R C AU - Raben, N AU - Plotz, P H AD - Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892-1820, USA. Y1 - 2001/01/19/ PY - 2001 DA - 2001 Jan 19 SP - 1789 EP - 1793 VL - 276 IS - 3 SN - 0021-9258, 0021-9258 KW - Basic Helix-Loop-Helix Transcription Factors KW - 0 KW - DNA Primers KW - DNA-Binding Proteins KW - Erythroid-Specific DNA-Binding Factors KW - Homeodomain Proteins KW - Repressor Proteins KW - Transcription Factor HES-1 KW - Transcription Factors KW - YY1 Transcription Factor KW - YY1 protein, human KW - HES1 protein, human KW - 149348-15-2 KW - alpha-Glucosidases KW - EC 3.2.1.20 KW - Index Medicus KW - Base Sequence KW - Transfection KW - Humans KW - Introns KW - Plasmids KW - Sequence Deletion KW - Gene Expression Regulation, Enzymologic KW - Transcription Factors -- metabolism KW - Homeodomain Proteins -- metabolism KW - Transcription, Genetic KW - Repressor Proteins -- genetics KW - alpha-Glucosidases -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70651152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transcriptional+regulation+of+the+human+acid+alpha-glucosidase+gene.+Identification+of+a+repressor+element+and+its+transcription+factors+Hes-1+and+YY1.&rft.au=Yan%2C+B%3BHeus%2C+J%3BLu%2C+N%3BNichols%2C+R+C%3BRaben%2C+N%3BPlotz%2C+P+H&rft.aulast=Yan&rft.aufirst=B&rft.date=2001-01-19&rft.volume=276&rft.issue=3&rft.spage=1789&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans. AN - 76969500; 11136236 AB - The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus SHIV(DH12R) induces a systemic depletion of CD4(+) T lymphocytes in rhesus monkeys during the initial 3-4 weeks of infection. Nonetheless, high levels of viral RNA production continue unabated for an additional 2-5 months. In situ hybridization and immunohistochemical analyses revealed that tissue macrophage in the lymph nodes, spleen, gastrointestinal tract, liver, and kidney sustain high plasma virus loads in the absence of CD4(+) T cells. Quantitative confocal immunofluorescence analysis indicated that greater than 95% of the virus-producing cells in these tissues are macrophage and less than 2% are T lymphocytes. Interestingly, the administration of a potent reverse transcriptase inhibitor blocked virus production during the early T cell phase but not during the later macrophage phase of the SHIV(DH12R) infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage as an important reservoir of virus in vivo. They become infected during the acute infection, gradually increase in number over time, and can be a major contributor to total body virus burden during the symptomatic phase of the human infection. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Igarashi, T AU - Brown, C R AU - Endo, Y AU - Buckler-White, A AU - Plishka, R AU - Bischofberger, N AU - Hirsch, V AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA. Y1 - 2001/01/16/ PY - 2001 DA - 2001 Jan 16 SP - 658 EP - 663 VL - 98 IS - 2 SN - 0027-8424, 0027-8424 KW - Anti-HIV Agents KW - 0 KW - Organophosphonates KW - RNA, Viral KW - Reverse Transcriptase Inhibitors KW - Tenofovir KW - 99YXE507IL KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - Virus Replication KW - Animals KW - Lymphoid Tissue -- pathology KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Digestive System -- virology KW - Disease Progression KW - Drug Resistance, Microbial KW - Organ Specificity KW - CD4 Lymphocyte Count KW - Viral Load KW - Chimera KW - Anti-HIV Agents -- pharmacology KW - Lymphoid Tissue -- virology KW - Organophosphonates -- pharmacology KW - Digestive System -- pathology KW - Adenine -- analogs & derivatives KW - RNA, Viral -- blood KW - Adenine -- pharmacology KW - Simian Immunodeficiency Virus -- genetics KW - Simian Immunodeficiency Virus -- physiology KW - HIV-1 -- genetics KW - Lentivirus Infections -- virology KW - HIV Infections -- virology KW - Simian Immunodeficiency Virus -- drug effects KW - Macrophages -- virology KW - Macaca mulatta -- virology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - Lentivirus Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76969500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Macrophage+are+the+principal+reservoir+and+sustain+high+virus+loads+in+rhesus+macaques+after+the+depletion+of+CD4%2B+T+cells+by+a+highly+pathogenic+simian+immunodeficiency+virus%2FHIV+type+1+chimera+%28SHIV%29%3A+Implications+for+HIV-1+infections+of+humans.&rft.au=Igarashi%2C+T%3BBrown%2C+C+R%3BEndo%2C+Y%3BBuckler-White%2C+A%3BPlishka%2C+R%3BBischofberger%2C+N%3BHirsch%2C+V%3BMartin%2C+M+A&rft.aulast=Igarashi&rft.aufirst=T&rft.date=2001-01-16&rft.volume=98&rft.issue=2&rft.spage=658&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1998 May;72(5):4265-73 [9557716] N Engl J Med. 1998 Mar 26;338(13):853-60 [9516219] Lancet. 1999 Jan 9;353(9147):119-20 [10023903] N Engl J Med. 1999 May 27;340(21):1605-13 [10341272] N Engl J Med. 1999 May 27;340(21):1614-22 [10341273] J Leukoc Biol. 1994 Sep;56(3):381-6 [8083612] J Virol. 1995 Feb;69(2):955-67 [7815563] Science. 1995 Nov 17;270(5239):1197-9 [7502044] J Virol. 1996 May;70(5):3189-97 [8627799] J Virol. 1996 Oct;70(10):6922-8 [8794335] J Virol. 1997 Feb;71(2):1608-20 [8995688] Nature. 1997 May 8;387(6629):188-91 [9144290] AIDS Res Hum Retroviruses. 1997 May 20;13(8):707-12 [9168239] Science. 1997 Jun 20;276(5320):1857-61 [9188531] J Leukoc Biol. 1997 Jul;62(1):138-43 [9226005] J Infect Dis. 1997 Aug;176(2):362-73 [9237701] N Engl J Med. 1997 Sep 11;337(11):734-9 [9287228] Science. 1997 Nov 14;278(5341):1291-5 [9360926] Science. 1997 Nov 14;278(5341):1295-300 [9360927] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7 [9371822] J Biol Regul Homeost Agents. 1997 Jan-Jun;11(1-2):69-73 [9418167] JAMA. 1999 Nov 3;282(17):1627-32 [10553788] Science. 1999 Nov 12;286(5443):1353-7 [10558989] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14049-54 [10570196] Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15109-14 [10611346] J Virol. 2000 Jul;74(14):6418-24 [10864653] J Virol. 2000 Aug;74(15):6935-45 [10888632] Nat Med. 2000 Jul;6(7):757-61 [10888923] J Clin Invest. 2000 Oct;106(7):839-45 [11018071] Science. 1986 Jul 11;233(4760):215-9 [3014648] Science. 1986 Sep 5;233(4768):1089-93 [3016903] Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089-93 [3018755] J Infect Dis. 1988 Jul;158(1):193-9 [2839582] J Exp Med. 1988 Sep 1;168(3):1111-25 [2844951] AIDS Res Hum Retroviruses. 1989 Aug;5(4):397-409 [2765298] J Med Virol. 1989 Nov;29(3):176-80 [2533247] Neurology. 1990 Feb;40(2):323-6 [2300258] AIDS Res Hum Retroviruses. 1990 Aug;6(8):967-71 [2223243] AIDS. 1992 Jan;6(1):65-70 [1543567] Neurology. 1992 Sep;42(9):1736-9 [1513462] J Virol. 1993 Apr;67(4):2182-90 [8445728] Lancet. 1994 Feb 12;343(8894):383-5 [7905551] J Virol. 1994 Jul;68(7):4409-19 [7515973] J Infect Dis. 1998 Aug;178(2):413-22 [9697721] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. AN - 70584901; 11177315 AB - Although concomitant alcoholism is widely believed to enhance liver disease progression in persons with hepatitis C virus (HCV) infection, this relationship has not been well quantified. To quantify the relationship of transfusion-associated HCV infection and history of heavy alcohol abuse to development of cirrhosis. Retrospective cohort study. Liver clinics in university and government hospitals. Extended follow-up of 1030 patients in prospective investigations of transfusion-associated viral hepatitis conducted in the United States between 1968 and 1980. Development of cirrhosis and history of heavy alcohol abuse were determined from review of interviews with patients or their proxies, medical records, death certificates, and autopsy and biopsy reports. Logistic regression was used to estimate the risk for cirrhosis associated with transfusion-associated HCV infection and history of heavy alcohol abuse. The absolute risk for cirrhosis was 17% among patients with transfusion-associated HCV; 3.2% among patients with transfusion-associated non-A, non-B, non-C hepatitis; and 2.8% among controls. Patients with transfusion-associated HCV were more likely than controls to develop cirrhosis (odds ratio, 7.8 [95% CI, 4.0 to 15.1]). A history of heavy alcohol abuse was associated with a fourfold increased risk for cirrhosis. Hepatitis C virus infection plus a history of heavy alcohol abuse led to a substantial increase in risk for cirrhosis (odds ratio, 31.1 [CI, 11.4 to 84.5]) compared with controls without such a history. Heavy alcohol abuse greatly exacerbates the risk for cirrhosis among patients with HCV infection. This finding emphasizes the need to counsel such patients about their drinking habits. JF - Annals of internal medicine AU - Harris, D R AU - Gonin, R AU - Alter, H J AU - Wright, E C AU - Buskell, Z J AU - Hollinger, F B AU - Seeff, L B AU - National Heart, Lung, and Blood Institute Study Group AD - Westat, 1650 Research Boulevard, Rockville, MD 20850, USA. ; National Heart, Lung, and Blood Institute Study Group Y1 - 2001/01/16/ PY - 2001 DA - 2001 Jan 16 SP - 120 EP - 124 VL - 134 IS - 2 SN - 0003-4819, 0003-4819 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Disease Progression KW - Retrospective Studies KW - Blood Transfusion -- adverse effects KW - Logistic Models KW - Risk Factors KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Male KW - Liver Cirrhosis, Alcoholic -- etiology KW - Hepatitis C -- complications KW - Hepatitis C -- etiology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70584901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=The+relationship+of+acute+transfusion-associated+hepatitis+to+the+development+of+cirrhosis+in+the+presence+of+alcohol+abuse.&rft.au=Harris%2C+D+R%3BGonin%2C+R%3BAlter%2C+H+J%3BWright%2C+E+C%3BBuskell%2C+Z+J%3BHollinger%2C+F+B%3BSeeff%2C+L+B%3BNational+Heart%2C+Lung%2C+and+Blood+Institute+Study+Group&rft.aulast=Harris&rft.aufirst=D&rft.date=2001-01-16&rft.volume=134&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-08 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. AN - 70652972; 11208854 AB - This phase I clinical trial was designed to determine the maximum-tolerated dose and dose-limiting toxicities of the matrix metalloproteinase (MMP) inhibitor COL-3 in patients with refractory solid tumors. Thirty-five patients with different cancer types were enrolled. COL-3 doses were escalated from 36 mg/m2/d in successive cohorts of at least three patients. Circulating levels of MMP-2, MMP-9, vascular endothelial growth factor, and basic fibroblast growth factor were assessed during treatment. Pharmacokinetic parameters were assessed for single and multiple doses of drug. Cutaneous phototoxicity was dose-limiting at 98 mg/m2/d. With the use of prophylactic sunblock, COL-3 was well tolerated at 70 mg/m2/d. The dose of 36 mg/m2/d was well tolerated without the use of sunblock. Other toxicities that did not seem to be related to dose or pharmacokinetics included anemia, anorexia, constipation, dizziness, elevated liver function test results, fever, headache, heartburn, nausea, vomiting, peripheral and central neurotoxicities, fatigue, and three cases of drug-induced lupus. Disease stabilization for periods of 26+ months, 8 months, and 6 months were seen in hemangioendothelioma, Sertoli-Leydig cell tumor, and fibrosarcoma, respectively. There was a potentially statistically significant relationship between changes in plasma MMP-2 levels and cumulative doses of drug when progressive disease patients were compared with those with stable disease or toxicity (P = .042). COL-3 induced disease stabilization in several patients who had a nonepithelial type of malignancy. Phototoxicity was dose-limiting. We recommend the dose of 36 mg/m2/d for phase II trials. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Rudek, M A AU - Figg, W D AU - Dyer, V AU - Dahut, W AU - Turner, M L AU - Steinberg, S M AU - Liewehr, D J AU - Kohler, D R AU - Pluda, J M AU - Reed, E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 584 EP - 592 VL - 19 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Endothelial Growth Factors KW - Enzyme Inhibitors KW - Lymphokines KW - Matrix Metalloproteinase Inhibitors KW - Tetracyclines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - tetracycline CMT-3 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Matrix Metalloproteinases KW - EC 3.4.24.- KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Index Medicus KW - Lymphokines -- blood KW - Humans KW - Aged KW - Matrix Metalloproteinase 2 -- blood KW - Matrix Metalloproteinase 9 -- blood KW - Adult KW - Fibroblast Growth Factor 2 -- blood KW - Middle Aged KW - Endothelial Growth Factors -- blood KW - Statistics, Nonparametric KW - Female KW - Male KW - Matrix Metalloproteinases -- blood KW - Neoplasms -- drug therapy KW - Enzyme Inhibitors -- therapeutic use KW - Tetracyclines -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Enzyme Inhibitors -- pharmacokinetics KW - Tetracyclines -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70652972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+clinical+trial+of+oral+COL-3%2C+a+matrix+metalloproteinase+inhibitor%2C+in+patients+with+refractory+metastatic+cancer.&rft.au=Rudek%2C+M+A%3BFigg%2C+W+D%3BDyer%2C+V%3BDahut%2C+W%3BTurner%2C+M+L%3BSteinberg%2C+S+M%3BLiewehr%2C+D+J%3BKohler%2C+D+R%3BPluda%2C+J+M%3BReed%2C+E&rft.aulast=Rudek&rft.aufirst=M&rft.date=2001-01-15&rft.volume=19&rft.issue=2&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multifunctional antioxidant activity of HBED iron chelator. AN - 70633573; 11163534 AB - The use of N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED) for iron chelation therapy is currently being tested. Besides its affinity for iron, bioavailability, and efficacy in relieving iron overload, it is important to assess its anti- and/or pro-oxidant activity. To address these questions, the antioxidant/pro-oxidant effects of HBED in a cell-free solution and on cultured Chinese hamster V79 cells were studied using UV-VIS spectrophotometry, oximetry, spin trapping, and electron paramagnetic resonance (EPR) spectrometry. The results indicate that HBED facilitates Fe(II) oxidation but blocks O2(.-)-induced reduction of Fe(III) and consequently pre-empts production of .OH or hypervalent iron through the Haber-Weiss reaction cycle. The efficacy of HBED as a 1-electron donor (H-donation) was demonstrated by reduction of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)-derived nitrogen-centered radical cation (ABTS(.+)), accompanied by formation of a short-lived phenoxyl radical. HBED also provided cytoprotection against toxicity of H2O2 and t-BuOOH. Our results show that HBED can act both as a H-donating antioxidant and as an effective chelator lacking pro-oxidant capacity, thus substantiating its promising use in iron chelation therapy. JF - Free radical biology & medicine AU - Samuni, A M AU - Afeworki, M AU - Stein, W AU - Yordanov, A T AU - DeGraff, W AU - Krishna, M C AU - Mitchell, J B AU - Brechbiel, M W AD - Radiation Biology Branch, Radiation Oncology Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 170 EP - 177 VL - 30 IS - 2 SN - 0891-5849, 0891-5849 KW - Antioxidants KW - 0 KW - Benzothiazoles KW - Chromans KW - Cyclic N-Oxides KW - Iron Chelating Agents KW - Phenols KW - Spin Labels KW - Sulfonic Acids KW - Superoxides KW - 11062-77-4 KW - 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid KW - 28752-68-3 KW - phenoxy radical KW - 3229-70-7 KW - Hydroxyl Radical KW - 3352-57-6 KW - N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid KW - 35998-29-9 KW - Hydrogen KW - 7YNJ3PO35Z KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Edetic Acid KW - 9G34HU7RV0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid KW - S18UL9710X KW - Oxygen KW - S88TT14065 KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Animals KW - Hydroxyl Radical -- metabolism KW - Oxygen -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Cytoprotection -- drug effects KW - Oxidation-Reduction KW - Superoxides -- metabolism KW - Cell Survival -- drug effects KW - Hydrogen -- metabolism KW - Spectrophotometry KW - Cricetulus KW - Hydrogen Peroxide -- metabolism KW - Phenols -- metabolism KW - tert-Butylhydroperoxide -- metabolism KW - Hydrogen Peroxide -- antagonists & inhibitors KW - Cell Death -- drug effects KW - tert-Butylhydroperoxide -- antagonists & inhibitors KW - Electron Spin Resonance Spectroscopy KW - Cyclic N-Oxides -- metabolism KW - tert-Butylhydroperoxide -- pharmacology KW - Sulfonic Acids -- metabolism KW - Chromans -- metabolism KW - Cell Line KW - Cricetinae KW - Edetic Acid -- analogs & derivatives KW - Antioxidants -- metabolism KW - Antioxidants -- pharmacology KW - Iron Chelating Agents -- metabolism KW - Iron Chelating Agents -- chemistry KW - Edetic Acid -- metabolism KW - Iron Chelating Agents -- pharmacology KW - Antioxidants -- chemistry KW - Edetic Acid -- pharmacology KW - Edetic Acid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70633573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Multifunctional+antioxidant+activity+of+HBED+iron+chelator.&rft.au=Samuni%2C+A+M%3BAfeworki%2C+M%3BStein%2C+W%3BYordanov%2C+A+T%3BDeGraff%2C+W%3BKrishna%2C+M+C%3BMitchell%2C+J+B%3BBrechbiel%2C+M+W&rft.aulast=Samuni&rft.aufirst=A&rft.date=2001-01-15&rft.volume=30&rft.issue=2&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1. AN - 70627312; 11160457 AB - Amyloid beta (Abeta) is a major contributor to the pathogenesis of Alzheimer's disease (AD). Although Abeta has been reported to be directly neurotoxic, it also causes indirect neuronal damage by activating mononuclear phagocytes (microglia) that accumulate in and around senile plaques. In this study, we show that the 42 amino acid form of beta amyloid peptide, Abeta(42), is a chemotactic agonist for a seven-transmembrane, G-protein-coupled receptor named FPR-Like-1 (FPRL1), which is expressed on human mononuclear phagocytes. Moreover, FPRL1 is expressed at high levels by inflammatory cells infiltrating senile plaques in brain tissues from AD patients. Thus, FPRL1 may mediate inflammation seen in AD and is a potential target for developing therapeutic agents. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Le, Y AU - Gong, W AU - Tiffany, H L AU - Tumanov, A AU - Nedospasov, S AU - Shen, W AU - Dunlop, N M AU - Gao, J L AU - Murphy, P M AU - Oppenheim, J J AU - Wang, J M AD - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, International Corporation Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 1 VL - 21 IS - 2 KW - Amyloid beta-Peptides KW - 0 KW - FPR2 protein, human KW - Gene Products, nef KW - Peptide Fragments KW - RNA, Messenger KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Lipoxin KW - Receptors, Peptide KW - Recombinant Fusion Proteins KW - Virulence Factors, Bordetella KW - amyloid beta-protein (1-42) KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Kidney -- drug effects KW - Gene Expression KW - Brain -- metabolism KW - Gene Products, nef -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Calcium -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Transfection KW - Brain -- pathology KW - Signal Transduction -- drug effects KW - Recombinant Fusion Proteins -- genetics KW - Kidney -- cytology KW - Cell Movement -- drug effects KW - Chemotaxis -- drug effects KW - Cell Line KW - Peptide Fragments -- metabolism KW - Receptors, Peptide -- metabolism KW - Receptors, Immunologic -- genetics KW - Amyloid beta-Peptides -- metabolism KW - GTP-Binding Proteins -- antagonists & inhibitors KW - Monocytes -- cytology KW - Receptors, Immunologic -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Amyloid beta-Peptides -- pharmacology KW - Monocytes -- metabolism KW - Peptide Fragments -- pharmacology KW - Receptors, Peptide -- genetics KW - Monocytes -- drug effects KW - Alzheimer Disease -- metabolism KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70627312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Amyloid+%28beta%2942+activates+a+G-protein-coupled+chemoattractant+receptor%2C+FPR-like-1.&rft.au=Le%2C+Y%3BGong%2C+W%3BTiffany%2C+H+L%3BTumanov%2C+A%3BNedospasov%2C+S%3BShen%2C+W%3BDunlop%2C+N+M%3BGao%2C+J+L%3BMurphy%2C+P+M%3BOppenheim%2C+J+J%3BWang%2C+J+M&rft.aulast=Le&rft.aufirst=Y&rft.date=2001-01-15&rft.volume=21&rft.issue=2&rft.spage=RC123&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of camptothecin-resistant mammalian cell lines to evaluate the role of topoisomerase I in the antiproliferative activity of the indolocarbazole, NB-506, and its topoisomerase I binding site. AN - 70581032; 11212241 AB - NB-506 is a topoisomerase I (top1) inhibitor in clinical trials. In this study, we used a series of camptothecin (CPT)-resistant cell lines with known top1 alterations. We show that three mutations in different domains of the top1 enzyme that confer CPT resistance also confer cross-resistance to NB-506. The CPT-resistant cell lines and corresponding mutations were: human prostate carcinoma cells DU-145/RC1 (mutation R364H), Chinese hamster fibroblasts DC3F/C10 (mutation G503S), and human leukemia CEM/C2 cells (N722S). This result suggests that NB-506 and CPT share a common binding site in the top1-DNA complex. We next used these three cell lines and their parental cells to study the relationship between top1 poisoning by NB-506 and antiproliferative activity. We found that the CPT-resistant cells were only 2-10-fold resistant to NB-506, which suggests that NB-506 targets other cellular processes/pathways besides top1. This conclusion was further supported by the limited cross-resistance of top1-deficient murine leukemia P388/CPT45 cells (2-fold). Cross-resistance was also limited for J-109,382, an isomer of NB-506 that does not intercalate into DNA, indicating that the non-top1-mediated antiproliferative activity of NB-506 is not attributable to DNA intercalation. Together, these data indicate that NB-506 and indolocarbazoles are promising agents to overcome CPT resistance. JF - Cancer research AU - Urasaki, Y AU - Laco, G AU - Takebayashi, Y AU - Bailly, C AU - Kohlhagen, G AU - Pommier, Y AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 504 EP - 508 VL - 61 IS - 2 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Carbazoles KW - DNA, Neoplasm KW - Glucosides KW - Intercalating Agents KW - NB 506 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Intercalating Agents -- pharmacology KW - DNA, Neoplasm -- drug effects KW - Stereoisomerism KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - DNA, Neoplasm -- genetics KW - Drug Resistance, Neoplasm KW - Mutation KW - DNA, Neoplasm -- metabolism KW - Binding Sites KW - Carbazoles -- chemistry KW - Camptothecin -- pharmacology KW - DNA Topoisomerases, Type I -- physiology KW - Carbazoles -- pharmacology KW - Glucosides -- chemistry KW - DNA Topoisomerases, Type I -- genetics KW - Antineoplastic Agents -- pharmacology KW - Glucosides -- pharmacology KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70581032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Use+of+camptothecin-resistant+mammalian+cell+lines+to+evaluate+the+role+of+topoisomerase+I+in+the+antiproliferative+activity+of+the+indolocarbazole%2C+NB-506%2C+and+its+topoisomerase+I+binding+site.&rft.au=Urasaki%2C+Y%3BLaco%2C+G%3BTakebayashi%2C+Y%3BBailly%2C+C%3BKohlhagen%2C+G%3BPommier%2C+Y&rft.aulast=Urasaki&rft.aufirst=Y&rft.date=2001-01-15&rft.volume=61&rft.issue=2&rft.spage=504&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium-induced malignant transformation of human prostate epithelial cells. AN - 70579178; 11212230 AB - Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in vitro and rapidly formed highly invasive and occasionally metastatic adenocarcinomas upon inoculation into mice. The transformed cells also showed increased secretion of MMP-2 and MMP-9, a phenomenon observed in human prostate tumors and linked to aggressive behavior. Cadmium-induced malignant transformation of human prostate epithelial cells strongly fortifies the evidence for a potential role of cadmium in prostate cancer. JF - Cancer research AU - Achanzar, W E AU - Diwan, B A AU - Liu, J AU - Quader, S T AU - Webber, M M AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 455 EP - 458 VL - 61 IS - 2 SN - 0008-5472, 0008-5472 KW - Cadmium KW - 00BH33GNGH KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Index Medicus KW - Adenocarcinoma -- metabolism KW - Animals KW - Humans KW - Mice KW - Mice, Nude KW - Neoplasms, Experimental -- metabolism KW - Neoplasms, Experimental -- pathology KW - Matrix Metalloproteinase 2 -- metabolism KW - Adenocarcinoma -- pathology KW - Neoplasm Transplantation KW - Matrix Metalloproteinase 9 -- metabolism KW - Prostate-Specific Antigen -- metabolism KW - Transplantation, Heterologous KW - Male KW - Prostate -- drug effects KW - Cadmium -- pharmacology KW - Prostate -- chemistry KW - Cell Transformation, Neoplastic -- pathology KW - Cell Transformation, Neoplastic -- chemically induced KW - Prostate -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70579178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Cadmium-induced+malignant+transformation+of+human+prostate+epithelial+cells.&rft.au=Achanzar%2C+W+E%3BDiwan%2C+B+A%3BLiu%2C+J%3BQuader%2C+S+T%3BWebber%2C+M+M%3BWaalkes%2C+M+P&rft.aulast=Achanzar&rft.aufirst=W&rft.date=2001-01-15&rft.volume=61&rft.issue=2&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load. AN - 70574444; 11120926 AB - To discern the T cell subtype associated with T cell differentiation, the expression of CD45RA and CD27 was measured from total CD8(high) cells and from human T cell lymphotropic virus type I (HTLV-I) Tax11-19 peptide-specific CD8(+) cells in peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phenotypically defined memory and/or effector cells (CD45RA(-)CD27(+), CD45RA(+)CD27(-), and CD45RA(-)CD27(-)) were increased in HAM/TSP CD8(+) cells, compared with those of HTLV-I-seronegative healthy control subjects. The percentage of human leukocyte antigen (HLA)-DR-positive cells was also increased in CD8(+) cells of HAM/TSP, compared with those in HLA-DR(+)CD8(+) cells of healthy control subjects. HTLV-I provirus load correlated with the frequency of Tax11-19-specific CD8(+) cells. The high frequency of memory and/or effector type HTLV-I Tax11-19-specific CD8(+) cells suggests that continuous restimulation driven by HTLV-I antigens in vivo may be associated with the pathogenesis of HAM/TSP. JF - The Journal of infectious diseases AU - Nagai, M AU - Kubota, R AU - Greten, T F AU - Schneck, J P AU - Leist, T P AU - Jacobson, S AD - Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 197 EP - 205 VL - 183 IS - 2 SN - 0022-1899, 0022-1899 KW - Antigens, CD27 KW - 0 KW - DNA, Viral KW - Gene Products, tax KW - HLA-A2 Antigen KW - Immunoglobulin G KW - Membrane Glycoproteins KW - Peptides KW - Pore Forming Cytotoxic Proteins KW - Perforin KW - 126465-35-8 KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Abridged Index Medicus KW - Index Medicus KW - Peptides -- chemical synthesis KW - Antigens, CD27 -- analysis KW - Humans KW - Peptides -- immunology KW - Viral Load KW - Lymphocyte Activation KW - HLA-A2 Antigen -- analysis KW - Adult KW - Antigens, CD45 -- analysis KW - Peptides -- chemistry KW - Cytotoxicity Tests, Immunologic KW - DNA, Viral -- blood KW - Middle Aged KW - Flow Cytometry KW - Immunoglobulin G -- metabolism KW - Proviruses KW - Female KW - Male KW - T-Lymphocytes, Regulatory -- immunology KW - Membrane Glycoproteins -- metabolism KW - Human T-lymphotropic virus 1 -- physiology KW - Gene Products, tax -- chemistry KW - Human T-lymphotropic virus 1 -- genetics KW - Paraparesis, Tropical Spastic -- immunology KW - Paraparesis, Tropical Spastic -- physiopathology KW - CD8-Positive T-Lymphocytes -- immunology KW - Immunologic Memory KW - CD8-Positive T-Lymphocytes -- classification KW - Human T-lymphotropic virus 1 -- isolation & purification KW - Human T-lymphotropic virus 1 -- immunology KW - Gene Products, tax -- immunology KW - Paraparesis, Tropical Spastic -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70574444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Increased+activated+human+T+cell+lymphotropic+virus+type+I+%28HTLV-I%29+Tax11-19-specific+memory+and+effector+CD8%2B+cells+in+patients+with+HTLV-I-associated+myelopathy%2Ftropical+spastic+paraparesis%3A+correlation+with+HTLV-I+provirus+load.&rft.au=Nagai%2C+M%3BKubota%2C+R%3BGreten%2C+T+F%3BSchneck%2C+J+P%3BLeist%2C+T+P%3BJacobson%2C+S&rft.aulast=Nagai&rft.aufirst=M&rft.date=2001-01-15&rft.volume=183&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potent and specific antitumor effects of an anti-CD22-targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma. AN - 70548035; 11154233 AB - LL2, an anti-CD22 monoclonal antibody against B-cell lymphoma, was covalently linked to the amphibian ribonuclease, onconase, a member of the pancreatic RNase A superfamily. LL2 increased in vitro potency (10 000-fold) and specificity against human Daudi Burkitt lymphoma cells while decreasing systemic toxicity of onconase. Monensin further increased potency of LL2-onconase on Daudi cells (IC(50), 20 and 1.5 pM, absence and presence of monensin, respectively). A 1-hour exposure to LL2-onconase was sufficient to kill Daudi cells in culture. These favorable in vitro properties translated to significant antitumor activity against disseminated Daudi lymphoma in mice with severe combined immunodeficiency disease. In mice inoculated with tumor cells intraperitoneally (ip), LL2-onconase (100 microg 5 times ip every day) increased the life span of animals with minimal disease 200%. The life span of mice with advanced disseminated Daudi lymphoma (tumor cells inoculated intravenously) was increased 135%. Mice injected with LL2-onconase tolerated a dose as high as 300 mg/kg. Because both onconase and LL2 are in clinical trials as cancer therapeutics, the covalently linked agents should be considered for treatment of non-Hodgkin lymphoma. JF - Blood AU - Newton, D L AU - Hansen, H J AU - Mikulski, S M AU - Goldenberg, D M AU - Rybak, S M AD - SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 528 EP - 535 VL - 97 IS - 2 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - Antineoplastic Agents KW - CD22 protein, human KW - Cd22 protein, mouse KW - Cell Adhesion Molecules KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - bectumomab KW - Ribonucleases KW - EC 3.1.- KW - ranpirnase KW - ZE15FIT23E KW - Abridged Index Medicus KW - Index Medicus KW - Models, Animal KW - Animals KW - Drug Stability KW - Immunotoxins -- toxicity KW - Dose-Response Relationship, Drug KW - Humans KW - Mice KW - Pancreas -- enzymology KW - Mice, Inbred BALB C KW - Cell Death -- drug effects KW - Neoplasm Transplantation KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Tumor Cells, Cultured KW - Survival Rate KW - Kinetics KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunotoxins -- therapeutic use KW - Mice, SCID KW - Immunotoxins -- pharmacology KW - Drug Evaluation, Preclinical KW - Antigens, CD -- immunology KW - Female KW - Ribonucleases -- toxicity KW - Antibodies, Monoclonal -- toxicity KW - Ribonucleases -- pharmacology KW - Ribonucleases -- therapeutic use KW - Antineoplastic Agents -- toxicity KW - Antibodies, Monoclonal -- pharmacology KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70548035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Potent+and+specific+antitumor+effects+of+an+anti-CD22-targeted+cytotoxic+ribonuclease%3A+potential+for+the+treatment+of+non-Hodgkin+lymphoma.&rft.au=Newton%2C+D+L%3BHansen%2C+H+J%3BMikulski%2C+S+M%3BGoldenberg%2C+D+M%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=2001-01-15&rft.volume=97&rft.issue=2&rft.spage=528&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic Activation of the Tumorigenic Alkaloid, Riddelliine, Leading to DNA Adduct Formation in Vivo AN - 17860225; 5105474 AB - Riddelliine is a representative naturally occurring genotoxic pyrrolizidine alkaloid. We have studied the mechanism by which riddelliine induces hepatocellular tumors in vivo. Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites. Metabolism was enhanced when liver microsomes from phenobarbital-treated rats were used. Metabolism in the presence of calf thymus DNA resulted in eight DNA adducts that were identical to those obtained from the reaction of DHR with calf thymus DNA. Two of these adducts were identified as DHR-modified 7-deoxyguanosin-N super(2)-yl epimers (DHR-3'-dGMP); the other six were DHR-derived DNA adducts, but their structures were not characterized. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose-response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR-3'-dGMP adducts. These results suggest that riddelliine induces liver tumors in rats through a genotoxic mechanism and the eight DHR-derived DNA adducts are likely to contribute to liver tumor development. JF - Chemical Research in Toxicology AU - Yang, Ya-Chen AU - Yan, Jian AU - Doerge AU - Chan, Po-Cheun AU - Fu, P P AU - Chou, Ming W AD - National Center for Toxicological Research, Jefferson, Arkansas 72079, and National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 101 EP - 109 VL - 14 IS - 1 SN - 0893-228X, 0893-228X KW - metabolites KW - metabolic activation KW - rats KW - Riddelliine KW - pyrrolizidine alkaloids KW - Toxicology Abstracts KW - DNA adducts KW - Alkaloids KW - Microsomes KW - Genotoxicity KW - Liver KW - Tumors KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17860225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Metabolic+Activation+of+the+Tumorigenic+Alkaloid%2C+Riddelliine%2C+Leading+to+DNA+Adduct+Formation+in+Vivo&rft.au=Yang%2C+Ya-Chen%3BYan%2C+Jian%3BDoerge%3BChan%2C+Po-Cheun%3BFu%2C+P+P%3BChou%2C+Ming+W&rft.aulast=Yang&rft.aufirst=Ya-Chen&rft.date=2001-01-15&rft.volume=14&rft.issue=1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Liver; Microsomes; Genotoxicity; Tumors; Alkaloids; DNA adducts ER - TY - JOUR T1 - Development of a super(32)P-Postlabeling/HPLC Method for Detection of Dehydroretronecine-Derived DNA Adducts in Vivo and in Vitro AN - 17860197; 5105473 AB - Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. Metabolism of pyrrolizidine alkaloids in vivo and in vitro generates dehydroretronecine (DHR) as a common reactive metabolite. In this study, we report the development of a super(32)P-postlabeling/HPLC method for detection of (i) two DHR-3'-dGMP and four DHR-3'-dAMP adducts and (ii) a set of eight DHR-derived DNA adducts in vitro and in vivo. The approach involves (1) synthesis of DHR-3'-dGMP, DHR-3'-dAMP, and DHR-3',5'-dG-bisphosphate standards and characterization of their structures by mass and super(1)H NMR spectral analyses, (2) development of optimal conditions for enzymatic DNA digestion, adduct enrichment, and super(32)P-postlabeling, and (3) development of optimal HPLC conditions. Using this methodology, we have detected eight DHR-derived DNA adducts, including the two epimeric DHR-3',5'-dG-bisphosphate adducts both in vitro and in vivo. JF - Chemical Research in Toxicology AU - Yang, Ya-Chen AU - Yan, Jian AU - Churchwell, M AU - Beger, R AU - Chan, Po-Cheun AU - Doerge AU - Fu, P P AU - Chou, Ming W AD - National Center for Toxicological Research, Jefferson, Arkansas 72079, and National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2001/01/15/ PY - 2001 DA - 2001 Jan 15 SP - 91 EP - 100 VL - 14 IS - 1 SN - 0893-228X, 0893-228X KW - Dehydroretronecine KW - pyrrolizidine alkaloids KW - Toxicology Abstracts KW - High-performance liquid chromatography KW - DNA adducts KW - Alkaloids KW - Radioisotopes KW - Plants KW - Genotoxicity testing KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17860197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Development+of+a+super%2832%29P-Postlabeling%2FHPLC+Method+for+Detection+of+Dehydroretronecine-Derived+DNA+Adducts+in+Vivo+and+in+Vitro&rft.au=Yang%2C+Ya-Chen%3BYan%2C+Jian%3BChurchwell%2C+M%3BBeger%2C+R%3BChan%2C+Po-Cheun%3BDoerge%3BFu%2C+P+P%3BChou%2C+Ming+W&rft.aulast=Yang&rft.aufirst=Ya-Chen&rft.date=2001-01-15&rft.volume=14&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Genotoxicity testing; Toxicity testing; Plants; Alkaloids; DNA adducts; High-performance liquid chromatography; Radioisotopes ER - TY - JOUR T1 - TOXNET: an evolving web resource for toxicology and environmental health information. AN - 70640365; 11164971 AB - TOXNET, developed by the National Library of Medicine (NLM), is a web-based system of databases providing information on toxicology, hazardous chemicals, and the environment. Databases fall under the general headings of Toxicology Data, Toxicology Literature, Toxic Releases, and Chemical Identification/Nomenclature. Among TOXNET's pre-eminent databases are the Hazardous Substances Data Bank (HSDB) and the TOXLINE file of bibliographic references. JF - Toxicology AU - Wexler, P AD - Toxicology and Environmental Health Information Program, National Institutes of Health, National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894, USA. wexlerp@mail.nlm.nih.gov Y1 - 2001/01/12/ PY - 2001 DA - 2001 Jan 12 SP - 3 EP - 10 VL - 157 IS - 1-2 SN - 0300-483X, 0300-483X KW - Index Medicus KW - Information Services KW - Environmental Health KW - Toxicology KW - Internet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70640365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=TOXNET%3A+an+evolving+web+resource+for+toxicology+and+environmental+health+information.&rft.au=Wexler%2C+P&rft.aulast=Wexler&rft.aufirst=P&rft.date=2001-01-12&rft.volume=157&rft.issue=1-2&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Searching fee and non-fee toxicology information resources: an overview of selected databases. AN - 70638639; 11164977 AB - Toxicology profiles organize information by broad subjects, the first of which affirms identity of the agent studied. Studies here show two non-fee databases (ChemFinder and ChemIDplus) verify the identity of compounds with high efficiency (63% and 73% respectively) with the fee-based Chemical Abstracts Registry file serving well to fill data gaps (100%). Continued searching proceeds using knowledge of structure, scope and content to select databases. Valuable sources for information are factual databases that collect data and facts in special subject areas organized in formats available for analysis or use. Some sources representative of factual files are RTECS, CCRIS, HSDB, GENE-TOX and IRIS. Numerous factual databases offer a wealth of reliable information; however, exhaustive searches probe information published in journal articles and/or technical reports with records residing in bibliographic databases such as BIOSIS, EMBASE, MEDLINE, TOXLINE and Web of Science. Listed with descriptions are numerous factual and bibliographic databases supplied by 11 producers. Given the multitude of options and resources, it is often necessary to seek service desk assistance. Questions were posed by telephone and e-mail to service desks at DIALOG, ISI, MEDLARS, Micromedex and STN International. Results of the survey are reported. JF - Toxicology AU - Wright, L L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. wrightl@niehs.nih.gov Y1 - 2001/01/12/ PY - 2001 DA - 2001 Jan 12 SP - 89 EP - 110 VL - 157 IS - 1-2 SN - 0300-483X, 0300-483X KW - Index Medicus KW - Occupational Health KW - Humans KW - Databases as Topic KW - Bibliography as Topic KW - Information Services KW - Toxicology KW - Internet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70638639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Searching+fee+and+non-fee+toxicology+information+resources%3A+an+overview+of+selected+databases.&rft.au=Wright%2C+L+L&rft.aulast=Wright&rft.aufirst=L&rft.date=2001-01-12&rft.volume=157&rft.issue=1-2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. AN - 70562376; 11150359 AB - Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth. JF - The New England journal of medicine AU - Stark, A R AU - Carlo, W A AU - Tyson, J E AU - Papile, L A AU - Wright, L L AU - Shankaran, S AU - Donovan, E F AU - Oh, W AU - Bauer, C R AU - Saha, S AU - Poole, W K AU - Stoll, B J AU - National Institute of Child Health and Human Development Neonatal Research Network AD - Brigham and Women's Hospital, Boston, MA 02115, USA. astark@uptodate.com ; National Institute of Child Health and Human Development Neonatal Research Network Y1 - 2001/01/11/ PY - 2001 DA - 2001 Jan 11 SP - 95 EP - 101 VL - 344 IS - 2 SN - 0028-4793, 0028-4793 KW - Anti-Inflammatory Agents KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Dexamethasone KW - 7S5I7G3JQL KW - Indomethacin KW - XXE1CET956 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Hypercapnia KW - Indomethacin -- adverse effects KW - Humans KW - Infant, Newborn KW - Respiration, Artificial KW - Infant Mortality KW - Indomethacin -- therapeutic use KW - Infant, Premature KW - Drug Therapy, Combination KW - Risk KW - Hypertension -- chemically induced KW - Intestinal Perforation -- chemically induced KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Chronic Disease KW - Male KW - Female KW - Growth -- drug effects KW - Infant, Very Low Birth Weight KW - Dexamethasone -- adverse effects KW - Anti-Inflammatory Agents -- adverse effects KW - Dexamethasone -- administration & dosage KW - Anti-Inflammatory Agents -- administration & dosage KW - Lung Diseases -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70562376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Adverse+effects+of+early+dexamethasone+in+extremely-low-birth-weight+infants.+National+Institute+of+Child+Health+and+Human+Development+Neonatal+Research+Network.&rft.au=Stark%2C+A+R%3BCarlo%2C+W+A%3BTyson%2C+J+E%3BPapile%2C+L+A%3BWright%2C+L+L%3BShankaran%2C+S%3BDonovan%2C+E+F%3BOh%2C+W%3BBauer%2C+C+R%3BSaha%2C+S%3BPoole%2C+W+K%3BStoll%2C+B+J%3BNational+Institute+of+Child+Health+and+Human+Development+Neonatal+Research+Network&rft.aulast=Stark&rft.aufirst=A&rft.date=2001-01-11&rft.volume=344&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-11 N1 - Date created - 2001-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular-telephone use and brain tumors AN - 17814855; 4847738 AB - Concern has arisen that the use of hand-held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices. We examined the use of cellular telephones in a case-control study of intracranial tumors of the nervous system conducted between 1994 and 1998. We enrolled 782 patients through hospitals in Phoenix, Arizona; Boston; and Pittsburgh; 489 had histologically confirmed glioma, 197 had meningioma, and 96 had acoustic neuroma. The 799 controls were patients admitted to the same hospitals as the patients with brain tumors for a variety of nonmalignant conditions. As compared with never, or very rarely, having used a cellular telephone, the relative risks associated with a cumulative use of a cellular telephone for more than 100 hours were 0.9 for glioma (95 percent confidence interval, 0.5 to 1.6), 0.7 for meningioma (95 percent confidence interval, 0.3 to 1.7), 1.4 for acoustic neuroma (95 percent confidence interval, 0.6 to 3.5), and 1.0 for all types of tumors combined (95 percent confidence interval, 0.6 to 1.5). There was no evidence that the risks were higher among persons who used cellular telephones for 60 or more minutes per day or regularly for five or more years. Tumors did not occur disproportionately often on the side of head on which the telephone was typically used. These data do not support the hypothesis that the recent use of hand-held cellular telephones causes brain tumors, but they are not sufficient to evaluate the risks among long-term, heavy users and for potentially long induction periods. JF - New England Journal of Medicine AU - Inskip, P D AU - Tarone, R E AU - Hatch, EE AU - Wilcosky, T C AU - Shapiro, W R AU - Selker, R G AU - Fine, HA AU - Black, P M AU - Loeffler, J S AU - Linet AD - Executive Plaza S., Rm. 7052, 6120 Executive Blvd., Rockville, MD 20852, USA, inskippe@mail.nih.gov Y1 - 2001/01/11/ PY - 2001 DA - 2001 Jan 11 SP - 79 EP - 86 VL - 344 IS - 2 SN - 0028-4793, 0028-4793 KW - man KW - cellular telephones KW - tumors KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Consumer products KW - Brain KW - Tumors KW - Cancer KW - Brain tumors KW - Hazards KW - X 24210:Radiation & radioactive materials KW - R2 23020:Technological risks KW - H 8000:Radiation Safety/Electrical Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17814855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+England+Journal+of+Medicine&rft.atitle=Cellular-telephone+use+and+brain+tumors&rft.au=Inskip%2C+P+D%3BTarone%2C+R+E%3BHatch%2C+EE%3BWilcosky%2C+T+C%3BShapiro%2C+W+R%3BSelker%2C+R+G%3BFine%2C+HA%3BBlack%2C+P+M%3BLoeffler%2C+J+S%3BLinet&rft.aulast=Inskip&rft.aufirst=P&rft.date=2001-01-11&rft.volume=344&rft.issue=2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Hazards; Brain; Consumer products; Risk assessment; Brain tumors; Tumors ER - TY - JOUR T1 - Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is critical for the high selectivity of the peptoid antagonist PD168368. AN - 70550578; 11013243 AB - Peptoid antagonists are increasingly being described for G protein-coupled receptors; however, little is known about the molecular basis of their binding. Recently, the peptoid PD168368 was found to be a potent selective neuromedin B receptor (NMBR) antagonist. To investigate the molecular basis for its selectivity for the NMBR over the closely related receptor for gastrin-releasing peptide (GRPR), we used a chimeric receptor approach and a site-directed mutagenesis approach. Mutated receptors were transiently expressed in Balb 3T3. The extracellular domains of the NMBR were not important for the selectivity of PD168368. However, substitution of the 5th upper transmembrane domain (uTM5) of the NMBR by the comparable GRPR domains decreased the affinity 16-fold. When the reverse study was performed by substituting the uTM5 of NMBR into the GRPR, a 9-fold increase in affinity occurred. Each of the 4 amino acids that differed between NMBR and GRPR in the uTM5 region were exchanged, but only the substitution of Phe(220) for Tyr in the NMBR caused a decrease in affinity. When the reverse study was performed to attempt to demonstrate a gain of affinity in the GRPR, the substitution of Tyr(219) for Phe caused an increase in affinity. These results suggest that the hydroxyl group of Tyr(220) in uTM5 of NMBR plays a critical role for high selectivity of PD168368 for NMBR over GRPR. Receptor and ligand modeling suggests that the hydroxyl of the Tyr(220) interacts with nitrophenyl group of PD168368 likely primarily by hydrogen bonding. This result shows the selectivity of the peptoid PD168368, similar to that reported for numerous non-peptide analogues with other G protein-coupled receptors, is primarily dependent on interaction with transmembrane amino acids. JF - The Journal of biological chemistry AU - Tokita, K AU - Hocart, S J AU - Katsuno, T AU - Mantey, S A AU - Coy, D H AU - Jensen, R T AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 2001/01/05/ PY - 2001 DA - 2001 Jan 05 SP - 495 EP - 504 VL - 276 IS - 1 SN - 0021-9258, 0021-9258 KW - Indoles KW - 0 KW - PD 168368 KW - Peptides KW - Peptoids KW - Pyridines KW - Receptors, Bombesin KW - Recombinant Fusion Proteins KW - Tyrosine KW - 42HK56048U KW - Neurokinin B KW - 86933-75-7 KW - neuromedin B KW - 87096-84-2 KW - Index Medicus KW - Point Mutation -- genetics KW - 3T3 Cells KW - Animals KW - Neurokinin B -- antagonists & inhibitors KW - Models, Molecular KW - Mutagenesis, Site-Directed -- genetics KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Neurokinin B -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Neurokinin B -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Transfection KW - Amino Acid Substitution -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Substrate Specificity KW - Protein Structure, Tertiary KW - Neurokinin B -- analogs & derivatives KW - Protein Conformation KW - Receptors, Bombesin -- genetics KW - Pyridines -- chemistry KW - Peptides -- chemistry KW - Tyrosine -- genetics KW - Indoles -- pharmacology KW - Tyrosine -- metabolism KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- antagonists & inhibitors KW - Peptides -- pharmacology KW - Pyridines -- pharmacology KW - Indoles -- chemistry KW - Receptors, Bombesin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70550578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Tyrosine+220+in+the+5th+transmembrane+domain+of+the+neuromedin+B+receptor+is+critical+for+the+high+selectivity+of+the+peptoid+antagonist+PD168368.&rft.au=Tokita%2C+K%3BHocart%2C+S+J%3BKatsuno%2C+T%3BMantey%2C+S+A%3BCoy%2C+D+H%3BJensen%2C+R+T&rft.aulast=Tokita&rft.aufirst=K&rft.date=2001-01-05&rft.volume=276&rft.issue=1&rft.spage=495&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2001-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo bone formation by human bone marrow stromal cells: Effect of carrier particle size and shape AN - 17847219; 4874701 AB - Successful closure of bone defects in patients remains an active area of basic and clinical research. A novel and promising approach is the transplantation of human bone marrow stromal cells (BMSCs), which have been shown to possess a significant osteogenic potential. The extent and quality of bone formation by transplanted human BMSCs strongly depends on the carrier matrix with which cells are transplanted; to date, hydroxyapatite/tricalcium phosphate (HA/TCP) supports far more osteogenesis than any other matrix tested. In order to further improve the technique of BMSC transplantation, we studied whether commercially available HA/TCP particles, clinically approved as an osteoconductive material and commercially available as particles measuring 0.5-1.0 mm diameter, is an optimum matrix for promoting bone development by BMSCs. HA/TCP and HA particles of varying size were sieved into a variety of size ranges, from 0.044 mm to 1.0-2.0 mm. Transplants were formed by mixing 40 mg aliquots of particles with cultured passaged human BMSCs. They were placed in subcutaneous pockets in immunocompromised Bg-Nu-XID mice and harvested 4 or 10 weeks later. The transplants were examined histologically; the presence of bone within each transplant was evaluated using histomorphometry or blindly scored on a semiquantitative scale. Transplant morphology and the amount of new bone varied in a consistent fashion based on particle size and shape. Transplants incorporating HA/TCP particles of 0.1-0.25 mm size demonstrated the greatest bone formation at both 4 and 10 weeks; larger or smaller particles were associated with less extensive bone formation, while a size of 0.044 mm represented a threshold below which no bone formation could be observed. Flat-sided HA particles measuring 0.1-0.25 mm formed no bone. The differences in bone formation were not attributable to the differences in cell attachment among the groups. Instead, the size and spatial and structural organization of the particles within BMSC transplants appear to determine the extent of bone formation. These findings provide necessary information for the successful clinical application of BMSC transplantation techniques. JF - Biotechnology and Bioengineering AU - Mankani, M H AU - Kuznetsov, SA AU - Fowler, B AU - Kingman, A AU - Robey, P G AD - Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA, mmankani@sfghsurg.ucsf.edu Y1 - 2001/01/05/ PY - 2001 DA - 2001 Jan 05 SP - 96 EP - 107 VL - 72 IS - 1 SN - 0006-3592, 0006-3592 KW - hydroxyapatite KW - tricalcium phosphate KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Stroma KW - Bone growth KW - Bone marrow KW - Osteogenesis KW - W 30965:Miscellaneous, Reviews KW - W2 32220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17847219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+and+Bioengineering&rft.atitle=In+vivo+bone+formation+by+human+bone+marrow+stromal+cells%3A+Effect+of+carrier+particle+size+and+shape&rft.au=Mankani%2C+M+H%3BKuznetsov%2C+SA%3BFowler%2C+B%3BKingman%2C+A%3BRobey%2C+P+G&rft.aulast=Mankani&rft.aufirst=M&rft.date=2001-01-05&rft.volume=72&rft.issue=1&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/10.1002%2F1097-0290%2820010105%2972%3A13.0.CO%3B2-A LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bone marrow; Stroma; Bone growth; Osteogenesis DO - http://dx.doi.org/10.1002/1097-0290(20010105)72:1<96::AID-BIT13>3.0.CO;2-A ER - TY - JOUR T1 - RECOVERY AND RECHALLENGE AFTER THE NEUROLEPTIC MALIGNANT SYNOROME AN - 872129094; 14536706 AB - The Neuroleptic Malignant Syndrome (NMS) can have a complicated recovery and rechallenging these patients is fraught with risks of recurrence. We examined our data from a sequential case series of NMS over a four-year period for details about treatment, complications and rechallenge. Duration of NMS when treated with one versus two dopamine agonists, and neuroleptic loading rates before NMS and on rechallenge were compared using the chi-square test with correction. Duration of NMS was found to be longer when treated with more than one agonist. The mean loading rate on rechallenge. attempted in six patients, was not found tc be statistically different from that resulting in NMS However, two patients (33%) re-challenged with high-potency neuroleptics at high loading rates experienced partial recurrence. Our findings show no advantage for treating NMS with multiple agents and emphasize the need for a cautious dosing strategy while re-challenging patients with typical neuroleptics. JF - Indian Journal of Psychiatry AU - Chopra, Mohit P AU - Raguram, R AD - P. CHOPRA, MD., DPM., Resident, Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore, 560029. Y1 - 2001///0, PY - 2001 DA - 0, 2001 SP - 41 EP - 45 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 43 IS - 1 SN - 0019-5545, 0019-5545 KW - Risk Abstracts; CSA Neurosciences Abstracts KW - Neuroleptic malignant syndrome KW - anti-psychotic KW - adverse reaction KW - complications KW - Data processing KW - Dopamine KW - Neuroleptics KW - N3 11001:Behavioral and Cognitive Neuroscience KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/872129094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+Journal+of+Psychiatry&rft.atitle=RECOVERY+AND+RECHALLENGE+AFTER+THE+NEUROLEPTIC+MALIGNANT+SYNOROME&rft.au=Chopra%2C+Mohit+P%3BRaguram%2C+R&rft.aulast=Chopra&rft.aufirst=Mohit&rft.date=2001-01-01&rft.volume=43&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Psychiatry&rft.issn=00195545&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-06-01 N1 - Last updated - 2016-07-07 N1 - SubjectsTermNotLitGenreText - Dopamine; Data processing; Neuroleptics; complications ER - TY - JOUR T1 - PET Evaluation of Bilingual Language Compensation following Early Childhood Brain Damage AN - 85509261; 200107524 AB - We report a positron emission tomography (PET) study in a 37-year-old, right handed, bilingual (English & American Sign Language [ASL]) male with left frontal lobe damage, without evidence of language or general intellectual dysfunction. A brain MRI scan demonstrated an atrophic lesion of the left dorsolateral prefrontal, orbital, & opercular cortices extending from the frontal pole to precentral gyrus & including parts of anterior cingulate cortex, due to an probable infantile encephalitis. H2 15O PET scans found evidence of increased right hemisphere activity compared to normal controls during spontaneous generation of narrative in both English & ASL. Neuropsychological data were within normal limits with the exception of visuospatial function. The results suggest the possibility that plasticity, unmasking of neural pathways, &/or other adaptations of language function in the right hemisphere may have occurred, & are discussed with regard to the crowding hypothesis. 3 Tables, 3 Figures, 43 References. Adapted from the source document JF - Neuropsychologia AU - Tierney, Michael C AU - Varga, Mary AU - Hosey, Lara AU - Grafman, Jordan AU - Braun, Allen AD - c/o Braun-Cognitive Neuroscience Section, Medical Neurology Branch, National Instit Neurological Disorders & Stroke, National Instits Health, Bethesda, MD ab10h@nih.gov Y1 - 2001///0, PY - 2001 DA - 0, 2001 SP - 114 EP - 121 VL - 39 IS - 2 SN - 0028-3932, 0028-3932 KW - Linguistic Competence (47400) KW - Brain Damage (09400) KW - Bilingualism (08850) KW - English (21900) KW - American Sign Language (02350) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85509261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychologia&rft.atitle=PET+Evaluation+of+Bilingual+Language+Compensation+following+Early+Childhood+Brain+Damage&rft.au=Tierney%2C+Michael+C%3BVarga%2C+Mary%3BHosey%2C+Lara%3BGrafman%2C+Jordan%3BBraun%2C+Allen&rft.aulast=Tierney&rft.aufirst=Michael&rft.date=2001-01-01&rft.volume=39&rft.issue=2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Neuropsychologia&rft.issn=00283932&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - NUPSA6 N1 - SubjectsTermNotLitGenreText - Bilingualism (08850); Brain Damage (09400); American Sign Language (02350); English (21900); Linguistic Competence (47400) ER - TY - JOUR T1 - Training agrammatic subjects on passive sentences: implications for syntactic deficit theories. AN - 85364974; pmid-11161354 AB - We trained two subjects with chronic agrammatic aphasia on production of passive sentences using a computerized, iconic-based communication system. After training, one of the subjects demonstrated significant improvements in his abilities to comprehend and verbally produce English passive voiced sentences, including sentences with conjoined subjects and objects. These results suggest that agrammatism does not represent a fixed syntactic deficit.Copyright 2001 Academic Press. JF - Brain and language AU - Weinrich, M AU - Boser, K I AU - McCall, D AU - Bishop, V AD - National Center for Medical Rehabilitation Research, National Institutes of Health, Rockville, MD 20852, USA. mw287k@nih.gov Y1 - 2001/01// PY - 2001 DA - Jan 2001 SP - 45 EP - 61 VL - 76 IS - 1 SN - 0093-934X, 0093-934X KW - Index Medicus KW - National Library of Medicine KW - Aged KW - *Aphasia, Broca: diagnosis KW - *Aphasia, Broca: rehabilitation KW - Brain: pathology KW - Brain: radiography KW - Chronic Disease KW - Female KW - Humans KW - Magnetic Resonance Imaging KW - Male KW - Neuropsychological Tests KW - *Psychological Theory KW - *Teaching KW - Tomography, X-Ray Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85364974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+language&rft.atitle=Training+agrammatic+subjects+on+passive+sentences%3A+implications+for+syntactic+deficit+theories.&rft.au=Weinrich%2C+M%3BBoser%2C+K+I%3BMcCall%2C+D%3BBishop%2C+V&rft.aulast=Weinrich&rft.aufirst=M&rft.date=2001-01-01&rft.volume=76&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Brain+and+language&rft.issn=0093934X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Prenatal neurobiological development: molecular mechanisms and anatomical change. AN - 85364664; pmid-11530976 AB - During prenatal development, the central nervous system is transformed from a thin layer of unspecified tissue into a complex system that can process information and organize actions. There are 8 general mechanisms that permit this transformation: neural induction, neurulation, proliferation, migration, axonal outgrowth, synaptogenesis, differentiation, and apoptosis. These processes as well as the anatomical changes they cause are described. Future research with humans, such as in utero MRI as well as behavioral and electrophysiological testing of infants following specific prenatal perturbations, is suggested to link the findings from molecular approaches to developmental neuropsychology. JF - Developmental neuropsychology AU - Monk, C S AU - Webb, S J AU - Nelson, C A AD - Institute of Child Development, University of Minnesota, USA. christopher.monk@nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 211 EP - 236 VL - 19 IS - 2 SN - 8756-5641, 8756-5641 KW - Index Medicus KW - National Library of Medicine KW - Apoptosis: physiology KW - Axons: physiology KW - Brain: anatomy & histology KW - Brain: cytology KW - *Brain: embryology KW - Cell Differentiation KW - Cell Movement: physiology KW - Humans KW - Synapses: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85364664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+neuropsychology&rft.atitle=Prenatal+neurobiological+development%3A+molecular+mechanisms+and+anatomical+change.&rft.au=Monk%2C+C+S%3BWebb%2C+S+J%3BNelson%2C+C+A&rft.aulast=Monk&rft.aufirst=C&rft.date=2001-01-01&rft.volume=19&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Developmental+neuropsychology&rft.issn=87565641&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Adductor muscle activity abnormalities in abductor spasmodic dysphonia. AN - 85358883; pmid-11228447 AB - To determine laryngeal muscle activation abnormalities associated with speech symptoms in abductor spasmodic dysphonia (ABSD).Bilateral laryngeal muscle recordings from the posterior cricoarytenoid, thyroarytenoid, and cricothyroid muscles were conducted in 12 ABSD patients. Patients' measures were compared during speech breaks and during speech without breaks and with 10 normal controls.Significant group differences were found in the thyroarytenoid muscle; the patients had significantly greater activity on the right side both during speech breaks and nonbreaks in comparison with the controls. Cricothyroid muscle levels were also increased on the right in the patients.An asymmetry in adductor muscle tone between the 2 sides in ABSD may account for difficulties with maintaining phonation and voice onset after voiceless consonants.These abnormalities may indicate why PCA BOTOX injections have not been as effective in ABSD as thyroarytenoid injections have been in adductor spasmodic dysphonia. JF - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery AU - Cyrus, C B AU - Bielamowicz, S AU - Evans, F J AU - Ludlow, C L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1416, USA. Y1 - 2001/01// PY - 2001 DA - Jan 2001 SP - 23 EP - 30 VL - 124 IS - 1 SN - 0194-5998, 0194-5998 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Aged KW - Botulinum Toxins, Type A: administration & dosage KW - Botulinum Toxins, Type A: therapeutic use KW - Electromyography KW - Female KW - Humans KW - Injections, Intramuscular KW - *Laryngeal Muscles: physiopathology KW - Male KW - Middle Aged KW - Muscle Tonus: physiology KW - Neuromuscular Agents: administration & dosage KW - Neuromuscular Agents: therapeutic use KW - Phonetics KW - Severity of Illness Index KW - Speech: physiology KW - *Voice Disorders: diagnosis KW - Voice Disorders: drug therapy KW - *Voice Disorders: physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85358883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--head+and+neck+surgery+%3A+official+journal+of+American+Academy+of+Otolaryngology-Head+and+Neck+Surgery&rft.atitle=Adductor+muscle+activity+abnormalities+in+abductor+spasmodic+dysphonia.&rft.au=Cyrus%2C+C+B%3BBielamowicz%2C+S%3BEvans%2C+F+J%3BLudlow%2C+C+L&rft.aulast=Cyrus&rft.aufirst=C&rft.date=2001-01-01&rft.volume=124&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--head+and+neck+surgery+%3A+official+journal+of+American+Academy+of+Otolaryngology-Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome. AN - 85280932; pmid-11152663 AB - Following the positional cloning of PDS, the gene mutated in the deafness/goitre disorder Pendred syndrome (PS), numerous studies have focused on defining the role of PDS in deafness and PS as well as elucidating the function of the PDS-encoded protein (pendrin). To facilitate these efforts and to provide a system for more detailed study of the inner-ear defects that occur in the absence of pendrin, we have generated a Pds-knockout mouse. Pds(-/-) mice are completely deaf and also display signs of vestibular dysfunction. The inner ears of these mice appear to develop normally until embryonic day 15, after which time severe endolymphatic dilatation occurs, reminiscent of that seen radiologically in deaf individuals with PDS mutations. Additionally, in the second postnatal week, severe degeneration of sensory cells and malformation of otoconia and otoconial membranes occur, as revealed by scanning electron and fluorescence confocal microscopy. The ultrastructural defects seen in the Pds(-/-) mice provide important clues about the mechanisms responsible for the inner-ear pathology associated with PDS mutations. JF - Human Molecular Genetics AU - Everett, L A AU - Belyantseva, I A AU - Noben-Trauth, K AU - Cantos, R AU - Chen, A AU - Thakkar, S I AU - Hoogstraten-Miller, S L AU - Kachar Bechara AU - Wu, Doris Kar-Wah AU - Green, E D AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.; National Institute on Deafness and Other Communication Disorders PY - 2001 SP - 153 EP - 161 VL - 10 IS - 2 SN - 0964-6906, 0964-6906 KW - Labyrinth KW - Goiter KW - Hair Cells KW - Carrier Proteins KW - Animal KW - Mice KW - Hearing Loss, Sensorineural KW - Vestibular Diseases KW - Thyroid Gland KW - Mice, Knockout KW - Syndrome KW - Mice, Neurologic Mutants KW - Vestibule KW - Microscopy, Electron, Scanning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85280932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Molecular+Genetics&rft.atitle=Targeted+disruption+of+mouse+Pds+provides+insight+about+the+inner-ear+defects+encountered+in+Pendred+syndrome.&rft.au=Everett%2C+L+A%3BBelyantseva%2C+I+A%3BNoben-Trauth%2C+K%3BCantos%2C+R%3BChen%2C+A%3BThakkar%2C+S+I%3BHoogstraten-Miller%2C+S+L%3BKachar+Bechara%3BWu%2C+Doris+Kar-Wah%3BGreen%2C+E+D&rft.aulast=Everett&rft.aufirst=L&rft.date=2001-01-01&rft.volume=10&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Human+Molecular+Genetics&rft.issn=09646906&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The role of somatostatin and octreotide in bowel obstruction: pre-clinical and clinical results. AN - 85254512; pmid-11669548 AB - Malignant bowel obstruction is a common complication in patients with advanced abdominal or pelvic cancer. Whereas surgery should be considered in all cases of malignant bowel obstruction, many advanced and terminal cancer patients are considered unfit for surgery. In such patients with a short life expectancy, gastrointestinal symptoms such as nausea, vomiting, continuous and/or colicky pain, can be controlled by using a pharmacologic approach made up of analgesics, antiemetics and antisecretory drugs, without the use of a venting nasogastric tube. Among the antisecretory drugs, octreotide has been shown to reduce nausea and vomiting in bowel-obstructed patients owing to a reduction of gastrointestinal secretions, thus allowing in most patients removal of the nasogastric tube and the associated distress. Preclinical and clinical studies that demonstrated the role of somatostatin and octreotide in bowel obstruction are reviewed. JF - Tumori AU - Ripamonti, C AU - Panzeri, C AU - Groff, L AU - Galeazzi, G AU - Boffi, R AD - Rehabilitation and Palliative Care Division, National Cancer Institute, Milan, Italy. PY - 2001 SP - 1 EP - 9 VL - 87 IS - 1 SN - 0300-8916, 0300-8916 KW - Vomiting KW - Abdominal Pain KW - Human KW - Animal KW - Gastrointestinal Agents KW - Octreotide KW - Butylscopolammonium Bromide KW - Intestinal Neoplasms KW - Somatostatin KW - Intestinal Obstruction KW - Treatment Outcome KW - Support, Non-U.S. Gov't KW - Nausea UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=The+role+of+somatostatin+and+octreotide+in+bowel+obstruction%3A+pre-clinical+and+clinical+results.&rft.au=Ripamonti%2C+C%3BPanzeri%2C+C%3BGroff%2C+L%3BGaleazzi%2C+G%3BBoffi%2C+R&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=2001-01-01&rft.volume=87&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. AN - 85236361; pmid-11090341 AB - Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22. Seven highly consanguineous families segregating nonsyndromic autosomal recessive deafness were analyzed to refine the DFNB12 locus. In a single family, a critical region was defined between D10S1694 and D10S1737, approximately 0.55 cM apart. Eighteen candidate genes in the region were sequenced. Mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in families with USH1D. Six missense mutations were found in five families with DFNB12, and two nonsense and two frameshift mutations were found in four families with USH1D. A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA. JF - American Journal of Human Genetics AU - Bork, J M AU - Peters, L M AU - Riazuddin, S AU - Bernstein, S L AU - Ahmed, Z M AU - Ness, S L AU - Polomeno, R AU - Ramesh, A AU - Schloss, M AU - Srisailpathy, C R AU - Wayne, S AU - Bellman, S AU - Desmukh, D AU - Ahmed, Z AU - Khan, S N AU - Kaloustian, V M AU - Li, X C AU - Lalwani, A AU - Bitner-Glindzicz, M AU - Nance, W E AU - Liu, X Z AU - Wistow, G AU - Smith, R J AU - Griffith, A J AU - Wilcox, E R AU - Friedman, Thomas B AU - Morell, R J AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 2001 SP - 26 EP - 37 VL - 68 IS - 1 SN - 0002-9297, 0002-9297 KW - Pedigree KW - Support, U.S. Gov't, P.H.S. KW - Gene Frequency KW - Exons KW - DNA Mutational Analysis KW - Human KW - Amino Acid Sequence KW - Hearing Loss, Sensorineural KW - Cadherins KW - Chromosome Mapping KW - RNA, Messenger KW - Base Sequence KW - Deafness KW - Consanguinity KW - Lod Score KW - Syndrome KW - DNA Primers KW - Retinitis Pigmentosa KW - Introns KW - Support, Non-U.S. Gov't KW - Mutation KW - Female KW - Male KW - Genes, Recessive KW - Alleles UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Human+Genetics&rft.atitle=Usher+syndrome+1D+and+nonsyndromic+autosomal+recessive+deafness+DFNB12+are+caused+by+allelic+mutations+of+the+novel+cadherin-like+gene+CDH23.&rft.au=Bork%2C+J+M%3BPeters%2C+L+M%3BRiazuddin%2C+S%3BBernstein%2C+S+L%3BAhmed%2C+Z+M%3BNess%2C+S+L%3BPolomeno%2C+R%3BRamesh%2C+A%3BSchloss%2C+M%3BSrisailpathy%2C+C+R%3BWayne%2C+S%3BBellman%2C+S%3BDesmukh%2C+D%3BAhmed%2C+Z%3BKhan%2C+S+N%3BKaloustian%2C+V+M%3BLi%2C+X+C%3BLalwani%2C+A%3BBitner-Glindzicz%2C+M%3BNance%2C+W+E%3BLiu%2C+X+Z%3BWistow%2C+G%3BSmith%2C+R+J%3BGriffith%2C+A+J%3BWilcox%2C+E+R%3BFriedman%2C+Thomas+B%3BMorell%2C+R+J&rft.aulast=Bork&rft.aufirst=J&rft.date=2001-01-01&rft.volume=68&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Human+Genetics&rft.issn=00029297&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cyclophosphamide for the treatment of systemic lupus erythematosus. AN - 77069911; 11315345 AB - Aggressive immunosuppressive therapy with cyclophosphamide has improved the outcome of major organ disease in lupus patients. Controlled trials have shown that pulse cyclophosphamide is the treatment of choice for patients with moderate to severe proliferative nephritis. Long-term follow-up of patients participating in these controlled trials suggests that combining pulse cyclophoshamide with pulse methylprednisolone increases efficacy but not toxicity. Retrospective case series have also shown that pulse cyclophosphamide therapy may be effective for the management of severe or refractory to standard therapy neuropsychiatric, pulmonary, cardiovascular and hematologic disease. Pulse cyclophosphamide is associated with an increased risk for herpes zoster infections in the short term and with sustained amenorrhea in the long-term. Recent studies have also drawn attention to the lack of response (or incomplete response) and flare of lupus after an initial response. In an effort to circumvent these limitations, current investigations explore the therapeutic potential of high-dose, immunoablative cyclophosphamide therapy or low-dose cyclophosphamide in combination with nucleoside analogs or biologic response modifiers. JF - Lupus AU - Takada, K AU - Illei, G G AU - Boumpas, D T AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 154 EP - 161 VL - 10 IS - 3 SN - 0961-2033, 0961-2033 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Humans KW - Cyclophosphamide -- therapeutic use KW - Lupus Erythematosus, Systemic -- drug therapy KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77069911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lupus&rft.atitle=Cyclophosphamide+for+the+treatment+of+systemic+lupus+erythematosus.&rft.au=Takada%2C+K%3BIllei%2C+G+G%3BBoumpas%2C+D+T&rft.aulast=Takada&rft.aufirst=K&rft.date=2001-01-01&rft.volume=10&rft.issue=3&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=Lupus&rft.issn=09612033&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-23 N1 - Date created - 2001-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Presence of potential nickel-responsive element(s) in the mouse MTH1 promoter. AN - 77064726; 11314867 AB - The murine MTH1 gene codes for MTH1, an 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) which hydrolyzes 8-oxo-dGTP, a promutagenic product of reactive oxygen species' attack on the nucleotide pool. This gene is regulated by oxidative stress. Therefore, we hypothesized that MTH1 expression can be affected by carcinogenic nickel(II), known to induce such stress. Three plasmid constructs, carrying different upstream regions of the mouse MTH1 and the chloramphenicol acetyltransferase (CAT) reporter gene, were transiently transfected into NIH 3T3 cells and the CAT protein was measured in nickel(II) acetate-treated and untreated cells. Nickel concentration-dependent increase of CAT protein level was observed for low Ni(II) concentrations, up to 400 microM Ni(II), in cells transfected with pHI103 plasmid (-5969 to +530 of the MTH1 sequence) only. Cells transfected with the pHI104 (-1331 to +530) or pHI108 (-151 to +530) plasmids did not respond to nickel(II) whatsoever. This finding demonstrated that the MTH1 sequence between -5969 and -1331 contained element(s) responsive to nickel(II) treatment. DNA sequencing revealed the presence of AP-1, NF-kappaB, and ATF-1 binding sites in both the -5969 to -1331 and -1331 to +530 regions. In contrast, two (CA)n repeats (-5642 to -5582 and -2078 to -2031), a family of B2 (-5428 to -5247) and B1 (-4559 to -4420) short interspersed repeated elements, and an (AT)n repeat (-5243 to -5230) were identified only in the -5969 to -1331 sequence. The results suggest that up-regulation of murine MTH1 expression by nickel(II) is controlled by the repeat sequences, potential candidates for nickel-responsive elements. JF - Annals of clinical and laboratory science AU - Liang, R AU - Igarashi, H AU - Tsuzuki, T AU - Nakabeppu, Y AU - Sekiguchi, M AU - Kasprzak, K S AU - Shiao, Y H AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 91 EP - 98 VL - 31 IS - 1 SN - 0091-7370, 0091-7370 KW - Acetates KW - 0 KW - Antimutagenic Agents KW - Organometallic Compounds KW - Recombinant Fusion Proteins KW - Transcription Factors KW - nickel acetate KW - 373-02-4 KW - Nickel KW - 7OV03QG267 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Mice KW - Binding Sites KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Gene Expression Regulation, Enzymologic KW - Transfection KW - Restriction Mapping KW - Oxidative Stress KW - Genes, Reporter KW - Molecular Sequence Data KW - Promoter Regions, Genetic -- drug effects KW - Organometallic Compounds -- pharmacology KW - Nickel -- pharmacology KW - Phosphoric Monoester Hydrolases -- genetics KW - Acetates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77064726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+clinical+and+laboratory+science&rft.atitle=Presence+of+potential+nickel-responsive+element%28s%29+in+the+mouse+MTH1+promoter.&rft.au=Liang%2C+R%3BIgarashi%2C+H%3BTsuzuki%2C+T%3BNakabeppu%2C+Y%3BSekiguchi%2C+M%3BKasprzak%2C+K+S%3BShiao%2C+Y+H&rft.aulast=Liang&rft.aufirst=R&rft.date=2001-01-01&rft.volume=31&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Annals+of+clinical+and+laboratory+science&rft.issn=00917370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delta opioid peptide augments functional effects and intrastriatal graft survival of rat fetal ventral mesencephalic cells. AN - 77038082; 11294472 AB - Delta enkephalin analogue [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to protect dopamine transporters from methamphetamine-induced neurotoxicity. In the present study, we demonstrate that exposure of embryonic ventral mesencephalic cells to DADLE (0.01 g/ml), prior to intrastriatal transplantation, enhanced functional recovery and graft survival in 6-hydroxydopamine-induced hemiparkinsonian rats. At 6 and 8 weeks posttransplantation, animals that received DADLE-treated cell grafts exhibited significantly higher (near normal) spontaneous locomotor behaviors, as well as trends of greater reversal of motor asymmetrical behaviors compared with animals that received nontreated cell grafts. Histological examination revealed that animals transplanted with DADLE-treated cell grafts exhibited about twice the number of surviving tyrosine hydroxylase-immunoreactive grafted neurons compared with those animals that received nontreated cell grafts. These results suggest that DADLE should be considered as an adjunctive agent for neural transplantation therapy in Parkinson's disease. JF - Cell transplantation AU - Borlongan, C V AU - Su, T P AU - Wang, Y AD - Cellular Neurobiology, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. cborlong@intra.nida.nih.gov PY - 2001 SP - 53 EP - 58 VL - 10 IS - 1 SN - 0963-6897, 0963-6897 KW - Enkephalin, Leucine-2-Alanine KW - 63631-40-3 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Mesencephalon -- transplantation KW - Corpus Striatum -- surgery KW - Mesencephalon -- pathology KW - Mesencephalon -- physiopathology KW - Dopamine -- physiology KW - Pregnancy KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Corpus Striatum -- physiopathology KW - Motor Activity -- drug effects KW - Corpus Striatum -- pathology KW - Female KW - Male KW - Parkinsonian Disorders -- physiopathology KW - Fetal Tissue Transplantation -- physiology KW - Fetal Tissue Transplantation -- pathology KW - Brain Tissue Transplantation -- methods KW - Enkephalin, Leucine-2-Alanine -- pharmacology KW - Fetal Tissue Transplantation -- methods KW - Brain Tissue Transplantation -- physiology KW - Parkinsonian Disorders -- surgery KW - Parkinsonian Disorders -- drug therapy KW - Parkinsonian Disorders -- pathology KW - Graft Survival -- drug effects KW - Brain Tissue Transplantation -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77038082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+transplantation&rft.atitle=Delta+opioid+peptide+augments+functional+effects+and+intrastriatal+graft+survival+of+rat+fetal+ventral+mesencephalic+cells.&rft.au=Borlongan%2C+C+V%3BSu%2C+T+P%3BWang%2C+Y&rft.aulast=Borlongan&rft.aufirst=C&rft.date=2001-01-01&rft.volume=10&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Cell+transplantation&rft.issn=09636897&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The hiccup reflex arc and persistent hiccups with high-dose anabolic steroids: is the brainstem the steroid-responsive locus? AN - 77036293; 11290884 AB - Hiccups have been classified as a neurologic reaction triggered by a multitude of factors. There are only a few reports of persistent hiccups associated with oral and intravenous corticosteroid use in the medical literature. It has been proposed that corticosteroids lower the threshold for synaptic transmission in the midbrain and directly stimulate the hiccup reflex arc. There is a recent report of progesterone-induced hiccups, which were thought to occur secondary to the glucocorticoid-like effects of progesterone on the brainstem. We report the first case of anabolic steroid-induced hiccups occurring in an elite power lifter. The hiccups occurred within 12 hours of the individual increasing his doses of oral anabolic steroids and persisted for 12 consecutive hours until medical attention was sought. In this report the pathophysiology of anabolic steroid-induced hiccups is discussed, and the postulated relationships of steroids and the hiccup reflex arc reviewed. JF - Clinical neuropharmacology AU - Dickerman, R D AU - Jaikumar, S AD - Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. PY - 2001 SP - 62 EP - 64 VL - 24 IS - 1 SN - 0362-5664, 0362-5664 KW - Anabolic Agents KW - 0 KW - Methandrostenolone KW - COZ1R7EOCC KW - Index Medicus KW - Administration, Oral KW - Methandrostenolone -- adverse effects KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Male KW - Brain Stem -- drug effects KW - Hiccup -- metabolism KW - Hiccup -- chemically induced KW - Brain Stem -- metabolism KW - Anabolic Agents -- metabolism KW - Anabolic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77036293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+neuropharmacology&rft.atitle=The+hiccup+reflex+arc+and+persistent+hiccups+with+high-dose+anabolic+steroids%3A+is+the+brainstem+the+steroid-responsive+locus%3F&rft.au=Dickerman%2C+R+D%3BJaikumar%2C+S&rft.aulast=Dickerman&rft.aufirst=R&rft.date=2001-01-01&rft.volume=24&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Clinical+neuropharmacology&rft.issn=03625664&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structure-based studies of cytosolic sulfotransferase. AN - 77019183; 11284047 AB - Sulfation is a widely observed biological reaction conserved from bacterium to human that plays a key role in various biological processes such as growth, development, and defense against adversities. Deficiencies due to the lack of the ubiquitous sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) are lethal in humans. A large group of enzymes called sulfotransferases catalyze the transfer reaction of sulfuryl group of PAPS to the acceptor group of numerous biochemical and xenochemical substrates. Four X-ray crystal structures of sulfotransferases have now been determined: cytosolic estrogen, hydroxysteroid, aryl sulfotransferases, and a sulfotransferase domain of the Golgi-membrane heparan sulfate N-deacetylase/N-sulfotransferase 1. These have revealed the conserved core structure of the PAPS binding site, a common reaction mechanism, and some information concerning the substrate specificity. These crystal structures introduce a new era of the study of the sulfotransferases. Copyright 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:67-75, 2001 JF - Journal of biochemical and molecular toxicology AU - Yoshinari, K AU - Petrotchenko, E V AU - Pedersen, L C AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 67 EP - 75 VL - 15 IS - 2 SN - 1095-6670, 1095-6670 KW - DNA, Complementary KW - 0 KW - Phosphoadenosine Phosphosulfate KW - 482-67-7 KW - Sulfotransferases KW - EC 2.8.2.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - DNA, Complementary -- genetics KW - Models, Molecular KW - Humans KW - Catalytic Domain KW - Mice KW - Crystallography, X-Ray KW - Substrate Specificity KW - Phosphoadenosine Phosphosulfate -- chemistry KW - Binding Sites KW - Sulfotransferases -- chemistry KW - Cytosol -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77019183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+and+molecular+toxicology&rft.atitle=Crystal+structure-based+studies+of+cytosolic+sulfotransferase.&rft.au=Yoshinari%2C+K%3BPetrotchenko%2C+E+V%3BPedersen%2C+L+C%3BNegishi%2C+M&rft.aulast=Yoshinari&rft.aufirst=K&rft.date=2001-01-01&rft.volume=15&rft.issue=2&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+and+molecular+toxicology&rft.issn=10956670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and pharmacodynamic effects of 5-fluorouracil given as a one-hour intravenous infusion. AN - 76998483; 11269737 AB - Clinical toxicity associated with 5-fluorouracil (5-FU) is related to the area under the plasma concentration-time curve (AUC). Recently, short-term infusions of 5-FU given over 30 or 60 min have been substituted for conventional "bolus" 5-FU given over 3-5 min in randomized clinical trials, but there are only limited pharmacokinetic data for these altered infusion durations. We therefore wished to determine the pharmacokinetics and toxicity associated with 5-FU given as a 1-h intravenous (i.v.) infusion. A group of 22 adults with advanced gastrointestinal tract cancers and no prior systemic chemotherapy for advanced disease received interferon alpha-2a (5 MU/m2 s.c., days 1-7), leucovorin (500 mg/m2 i.v. over 30 min, days 2-6) and 5-FU (370 mg/m2 i.v. over 1 h, days 2-6). The doses of 5-FU and interferon-alpha were adjusted according to individual tolerance. The pharmacokinetics and clinical toxicity were retrospectively compared with patients receiving the same regimen under the same treatment guidelines except that 5-FU was given over 5 min. The regimen was well tolerated, and 41% of the patients tolerated 5-FU dose escalations to 425-560 mg/m2 per day. Grade 3 or worse diarrhea and fatigue ultimately occurred in 14% of the patients each. Granulocytopenia, mucositis, and diarrhea appeared to be appreciably milder in the present trial compared with our prior phase II experience in colorectal cancer. The peak 5-FU plasma levels and AUC with 370 mg/m2 5-FU given over 1 h were 7.3-fold and 2.4-fold lower than previously measured in 31 patients who received 5-FU over 5 min. Increasing the length of 5-FU infusion to 1 h seemed to substantially reduce the clinical toxicity with this modulated 5-FU regimen, likely due to markedly lower peak 5-FU plasma levels and AUC. Changes in the duration of a short infusion of 5-FU clearly affects the clinical toxicity, but raises the concern of a potentially adverse impact on its antitumor activity. These results suggest the importance of including precise guidelines concerning the time over which 5-FU is given in clinical trials. Having a specified duration of 5-FU infusion is also important if 5-FU dose escalation is considered. JF - Cancer chemotherapy and pharmacology AU - Grem, J L AU - Quinn, M AU - Ismail, A S AU - Takimoto, C H AU - Lush, R AU - Liewehr, D J AU - Steinberg, S M AU - Balis, F M AU - Chen, A P AU - Monahan, B P AU - Harold, N AU - Corse, W AU - Pang, J AU - Murphy, R F AU - Allegra, C J AU - Hamilton, J M AD - National Cancer Institute-Medicine Branch, National Naval Medical Center, Bethesda, MD 20889, USA. jgrem@helix.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 117 EP - 125 VL - 47 IS - 2 SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Infusions, Intravenous KW - Area Under Curve KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Fluorouracil -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76998483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Pharmacokinetics+and+pharmacodynamic+effects+of+5-fluorouracil+given+as+a+one-hour+intravenous+infusion.&rft.au=Grem%2C+J+L%3BQuinn%2C+M%3BIsmail%2C+A+S%3BTakimoto%2C+C+H%3BLush%2C+R%3BLiewehr%2C+D+J%3BSteinberg%2C+S+M%3BBalis%2C+F+M%3BChen%2C+A+P%3BMonahan%2C+B+P%3BHarold%2C+N%3BCorse%2C+W%3BPang%2C+J%3BMurphy%2C+R+F%3BAllegra%2C+C+J%3BHamilton%2C+J+M&rft.aulast=Grem&rft.aufirst=J&rft.date=2001-01-01&rft.volume=47&rft.issue=2&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preparation and preclinical characterization of RNase-based immunofusion proteins. AN - 76995520; 11265299 JF - Methods in molecular biology (Clifton, N.J.) AU - Newton, D L AU - Rybak, S M AD - SAIC Frederick, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 387 EP - 406 VL - 160 SN - 1064-3745, 1064-3745 KW - Immunotoxins KW - 0 KW - Recombinant Fusion Proteins KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Recombinant Fusion Proteins -- analysis KW - Animals KW - Humans KW - Immunotoxins -- analysis KW - Ribonucleases -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76995520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Preparation+and+preclinical+characterization+of+RNase-based+immunofusion+proteins.&rft.au=Newton%2C+D+L%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=2001-01-01&rft.volume=160&rft.issue=&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-12 N1 - Date created - 2001-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbohydrate-deficient transferrin: an aid to early recognition of alcohol relapse. AN - 76995463; 11268818 AB - Although the primary use of biochemical markers of heavy drinking is to assist in screening for alcohol problems, laboratory tests may also aid in early identification of relapse. This report reviews research findings on a new marker, carbohydrate deficient transferrin (CDT), in alcoholics receiving treatment or in follow-up. It also offers recommendations on how CDT may be employed by clinicians monitoring drinking status. JF - The American journal on addictions AU - Allen, J P AU - Litten, R Z AU - Fertig, J B AU - Sillanaukee, P AD - Division of Clinical and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Willco Building, Suite 505, 6000 Executive Blvd., MSC 7003, Bethesda, MD 20892-7003, USA. jallen@willco.niaaa.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 24 EP - 28 VL - 10 Suppl SN - 1055-0496, 1055-0496 KW - Biomarkers KW - 0 KW - Transferrin KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Index Medicus KW - Humans KW - Time Factors KW - Biomarkers -- blood KW - Secondary Prevention KW - Transferrin -- metabolism KW - Transferrin -- analogs & derivatives KW - Alcoholism -- enzymology KW - Alcoholism -- diagnosis KW - gamma-Glutamyltransferase -- metabolism KW - Guidelines as Topic KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76995463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+on+addictions&rft.atitle=Carbohydrate-deficient+transferrin%3A+an+aid+to+early+recognition+of+alcohol+relapse.&rft.au=Allen%2C+J+P%3BLitten%2C+R+Z%3BFertig%2C+J+B%3BSillanaukee%2C+P&rft.aulast=Allen&rft.aufirst=J&rft.date=2001-01-01&rft.volume=10+Suppl&rft.issue=&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer proteomics: from biomarker discovery to signal pathway profiling. AN - 76993644; 11269650 AB - In the post-genomic era of science, the field of proteomics promises the discovery of new molecular targets for therapy, biomarkers for early detection, and new endpoints for therapeutic efficacy and toxicity. Patient-specific targeted therapeutics with reduced toxicity and increased efficacy, the ultimate goal for rational drug development, can only be achieved if direct analyses of the tissue cells in the actual human malignancy are analyzed. To that end, technologies such as Laser Capture Microdissection (LCM), is providing unparalleled access to the purified diseased human cells directly from tissue specimens. However, limited availability of patient material is a challenge towards the development of new highly sensitive proteomic methodologies. Two-dimensional gel electrophoresis (2D-PAGE), still the mainstay of most proteomic analysis of disease, is being complemented, and in some instances replaced by new exciting approaches to multiparametric protein characterization. The use of rapid, high throughput mass spectrometric-based fingerprints of peptides and proteins may prove to be valuable for new molecular classification of human tumors and disease stages. Coupled with LCM, high-density protein arrays, antibody arrays, and small molecular arrays, could have a substantial impact on proteomic profiling of human malignancies. Finally, detailed real-time knowledge about the states of intracellular signaling circuitry and pathways in the normal and malignant cells before, during and after therapy will yield invaluable information about mechanism of action and efficacy of existing and novel therapeutics for the treatment of human cancer. JF - Cancer journal (Sudbury, Mass.) AU - Bichsel, V E AU - Liotta, L A AU - Petricoin, E F AD - Laboratory of Pathology, NCI, NIH, Bethesda, MD 20892, USA. PY - 2001 SP - 69 EP - 78 VL - 7 IS - 1 SN - 1528-9117, 1528-9117 KW - Biomarkers KW - 0 KW - Biomarkers, Tumor KW - Neoplasm Proteins KW - Proteome KW - Index Medicus KW - Proteome -- genetics KW - Peptide Mapping -- methods KW - Electrophoresis, Gel, Two-Dimensional -- methods KW - Humans KW - Biomarkers -- analysis KW - Proteome -- metabolism KW - Cell Separation KW - Biomarkers, Tumor -- metabolism KW - Signal Transduction -- physiology KW - Neoplasms -- chemistry KW - Biomarkers, Tumor -- analysis KW - Neoplasm Proteins -- analysis KW - Neoplasm Proteins -- metabolism KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76993644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.atitle=Cancer+proteomics%3A+from+biomarker+discovery+to+signal+pathway+profiling.&rft.au=Bichsel%2C+V+E%3BLiotta%2C+L+A%3BPetricoin%2C+E+F&rft.aulast=Bichsel&rft.aufirst=V&rft.date=2001-01-01&rft.volume=7&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.issn=15289117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactivation of chronic hepatitis B infection following intensive chemotherapy and successful treatment with lamivudine: a case report and review of the literature. AN - 76968792; 11249039 AB - Hepatitis B virus reactivation has been reported in cancer patients following administration of chemotherapy or immunosuppressive therapy and may result in liver damage of varying degrees of severity. Although treatment is supportive in nature, lamivudine, a nucleoside analogue has been found to suppress HBV replication as evidenced by reports of 13 cases in the medical literature. We report a patient who achieved a successful outcome with lamivudine following reactivation of HBV during combination chemotherapy for non-Hodgkin's lymphoma, and provide a brief overview of the literature including the 13 published case reports. Lamivudine therapy resulted in clinical improvement as well as in normalization of liver function tests and coagulation profile. Lamivudine has been found to suppress HBV replication manifested both by histology and serum HBV-DNA levels in chronic carriers of HBV who developed reactivation of hepatic disease following chemotherapy. Physicians caring for such patients should be able to recognize this clinical challenge, and lamivudine should be considered. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Saif, M W AU - Little, R F AU - Hamilton, J M AU - Allegra, C J AU - Wilson, W H AD - Medicine Branch, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889, USA. saifw@mail.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 123 EP - 129 VL - 12 IS - 1 SN - 0923-7534, 0923-7534 KW - Reverse Transcriptase Inhibitors KW - 0 KW - Lamivudine KW - 2T8Q726O95 KW - Index Medicus KW - Liver -- virology KW - Liver -- pathology KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Recurrence KW - Male KW - Female KW - Hepatitis B, Chronic -- etiology KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Hepatitis B, Chronic -- pathology KW - Lamivudine -- therapeutic use KW - Immunocompromised Host KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - Lymphoma, Non-Hodgkin -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Hepatitis B, Chronic -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76968792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Reactivation+of+chronic+hepatitis+B+infection+following+intensive+chemotherapy+and+successful+treatment+with+lamivudine%3A+a+case+report+and+review+of+the+literature.&rft.au=Saif%2C+M+W%3BLittle%2C+R+F%3BHamilton%2C+J+M%3BAllegra%2C+C+J%3BWilson%2C+W+H&rft.aulast=Saif&rft.aufirst=M&rft.date=2001-01-01&rft.volume=12&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydrocortisone suspension and hydrocortisone tablets are not bioequivalent in the treatment of children with congenital adrenal hyperplasia. AN - 76968532; 11232038 AB - In July 1998, Cortef oral suspension (Pharmacia & Upjohn) was reformulated changing the suspending agent tragacanth to xanthan gum. We subsequently observed suboptimal control of hormone levels in a group of children with classic congenital adrenal hyperplasia, despite increasing doses of Cortef suspension and stringent instructions to parents regarding shaking of the bottles of medication. Nineteen children receiving Cortef and fludrocortisone therapy were changed to hydrocortisone tablets and fludrocortisone, with a 10 percent reduction in hydrocortisone dose. A significant decrease in 17-hydroxyprogesterone (235 +/- 120 vs. 27 +/- 7 nmol/L; p 0 for the period 9-32 years before the event. The estimated latency curve was homogeneous across categories of attained age, duration of exposure, rate of exposure, and smoking. The proposed spline model is a flexible tool for latency analyses, and extends previously used methods. JF - Journal of epidemiology and biostatistics AU - Hauptmann, M AU - Berhane, K AU - Langholz, B AU - Lubin, J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD 20892-7244, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 417 EP - 424 VL - 6 IS - 6 SN - 1359-5229, 1359-5229 KW - Air Pollutants, Radioactive KW - 0 KW - Carcinogens, Environmental KW - Uranium KW - 4OC371KSTK KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Half-Life KW - Epidemiologic Studies KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Statistics as Topic KW - Environmental Exposure -- adverse effects KW - Uranium -- adverse effects KW - Time Factors KW - Colorado -- epidemiology KW - Risk Assessment KW - Mining -- statistics & numerical data KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms, Radiation-Induced -- epidemiology KW - Occupational Diseases -- etiology KW - Occupational Diseases -- epidemiology KW - Air Pollutants, Radioactive -- adverse effects KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72422035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+epidemiology+and+biostatistics&rft.atitle=Using+splines+to+analyse+latency+in+the+Colorado+Plateau+uranium+miners+cohort.&rft.au=Hauptmann%2C+M%3BBerhane%2C+K%3BLangholz%2C+B%3BLubin%2C+J&rft.aulast=Hauptmann&rft.aufirst=M&rft.date=2001-01-01&rft.volume=6&rft.issue=6&rft.spage=417&rft.isbn=&rft.btitle=&rft.title=Journal+of+epidemiology+and+biostatistics&rft.issn=13595229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-30 N1 - Date created - 2002-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol-related birth defects--the past, present, and future. AN - 72418427; 11810952 AB - In 1994 Alcohol Health & Research World (now titled Alcohol Research & Health) last devoted a full issue to the topic of fetal alcohol syndrome (FAS) and other alcohol-related birth defects (ARBD). This introductory article provides readers with information on how the field has advanced since then. In addition to tracing the development of the terminology used in the field, it describes the difficulties involved in determining the true prevalence of FAS and ARBD; the mechanisms that may play a role in alcohol-derived fetal injuries; approaches to preventing drinking during pregnancy; and strategies for assisting people who have been born with FAS and ARBD. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Warren, K R AU - Foudin, L L AD - Office of Scientific Affairs, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 153 EP - 158 VL - 25 IS - 3 SN - 1535-7414, 1535-7414 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Maternal Behavior KW - Pregnancy Complications -- prevention & control KW - Humans KW - Alcohol Drinking -- adverse effects KW - Forecasting KW - Alcohol Drinking -- prevention & control KW - Research KW - Alcoholism -- prevention & control KW - Alcoholism -- complications KW - Female KW - Prevalence KW - Pregnancy KW - Abnormalities, Drug-Induced -- diagnosis KW - Ethanol -- adverse effects KW - Abnormalities, Drug-Induced -- epidemiology KW - Abnormalities, Drug-Induced -- rehabilitation KW - Fetal Alcohol Spectrum Disorders -- rehabilitation KW - Terminology as Topic KW - Fetal Alcohol Spectrum Disorders -- epidemiology KW - Fetal Alcohol Spectrum Disorders -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72418427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Alcohol-related+birth+defects--the+past%2C+present%2C+and+future.&rft.au=Warren%2C+K+R%3BFoudin%2C+L+L&rft.aulast=Warren&rft.aufirst=K&rft.date=2001-01-01&rft.volume=25&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-28 N1 - Date created - 2002-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular targets for selenium in cancer prevention. AN - 72401380; 11799923 AB - Mounting evidence reveals that selenium is a dietary constituent with anticarcinogenic and antitumorigenic properties. Various forms of selenium appear to be effective in bringing about these effects, although preclinical studies suggest that differences may arise as the quantity provided is reduced. The literature also documents the greater sensitivity of neoplastic cells to selenium than their nonneoplastic counterparts. Unfortunately, the minimal amount needed to bring about a positive effect in humans remains elusive. If there is a positive response to exaggerated intakes, it will likely be dependent on many factors, including the consumption of other dietary constituents, as well as variation in a host of genetic pathways involved with cancer. Although the biological basis of the reduction in cancer risk ascribed to selenium remains to be established, its consistency in retarding various experimentally induced tumors and suppressing the growth of various types of neoplasms in vitro and in vivo suggests that several mechanisms are involved. Depressed carcinogen bioactivation, reduced cell proliferation, and increased apoptosis raise the possibility that selenium works at a number of specific molecular targets involved with the cancer process. This review will focus on molecular targets involved with cell proliferation and apoptosis as possible mechanisms by which selenium might alter the cancer process. JF - Nutrition and cancer AU - Kim, Y S AU - Milner, J AD - Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 50 EP - 54 VL - 40 IS - 1 SN - 0163-5581, 0163-5581 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - Antioxidants KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - NF-kappa B KW - Proteins KW - Transcription Factor AP-1 KW - Lipoxygenase KW - EC 1.13.11.12 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Animals KW - Transcription Factor AP-1 -- antagonists & inhibitors KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Proteins -- antagonists & inhibitors KW - Lipoxygenase -- drug effects KW - Apoptosis -- drug effects KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Dietary Supplements KW - NF-kappa B -- antagonists & inhibitors KW - Selenium -- chemistry KW - Antioxidants -- pharmacology KW - Antineoplastic Agents -- administration & dosage KW - Anticarcinogenic Agents -- pharmacology KW - Selenium -- pharmacology KW - Neoplasms -- prevention & control KW - Selenium -- administration & dosage KW - Antineoplastic Agents -- pharmacology KW - Anticarcinogenic Agents -- administration & dosage KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72401380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Molecular+targets+for+selenium+in+cancer+prevention.&rft.au=Kim%2C+Y+S%3BMilner%2C+J&rft.aulast=Kim&rft.aufirst=Y&rft.date=2001-01-01&rft.volume=40&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-10 N1 - Date created - 2002-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug abuse and addiction in internal medicine. AN - 72400003; 11795077 JF - Advances in internal medicine AU - Francis, H L AU - Leshner, A I AD - Center on AIDS and Other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Md., USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 239 EP - 263 VL - 47 SN - 0065-2822, 0065-2822 KW - Street Drugs KW - 0 KW - Index Medicus KW - Acquired Immunodeficiency Syndrome -- complications KW - Drug Interactions KW - Humans KW - Street Drugs -- adverse effects KW - Internal Medicine KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- therapy KW - Primary Health Care KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72400003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+internal+medicine&rft.atitle=Drug+abuse+and+addiction+in+internal+medicine.&rft.au=Francis%2C+H+L%3BLeshner%2C+A+I&rft.aulast=Francis&rft.aufirst=H&rft.date=2001-01-01&rft.volume=47&rft.issue=&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Advances+in+internal+medicine&rft.issn=00652822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-10 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene x environment interaction from case-control and case-case approaches. AN - 72399907; 11793787 AB - Using the Genetic Analysis Workshop 12 data, we applied case-control and case-case approaches to study the effects of a major gene and its interaction with sex on the disease liability. Although no joint additive effect was simulated, the case-case approach detected a small but significant multiplicative interaction effect, which could not be explained by the effect of random error. Given that analyses of "real" data will not be made with the knowledge of the true effects a priori, this study showed that the measure of gene x environment interaction is critical and the definition of interaction should be explicit. JF - Genetic epidemiology AU - Bai, Y AU - Goldin, L R AU - Goldstein, A M AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Bethesda, MD 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - S825 EP - S830 VL - 21 Suppl 1 SN - 0741-0395, 0741-0395 KW - Index Medicus KW - Quantitative Trait, Heritable KW - Phenotype KW - Odds Ratio KW - Sex Factors KW - Lod Score KW - Humans KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Male KW - Female KW - Genotype KW - Genetic Predisposition to Disease -- genetics KW - Models, Genetic KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72399907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+epidemiology&rft.atitle=Gene+x+environment+interaction+from+case-control+and+case-case+approaches.&rft.au=Bai%2C+Y%3BGoldin%2C+L+R%3BGoldstein%2C+A+M&rft.aulast=Bai&rft.aufirst=Y&rft.date=2001-01-01&rft.volume=21+Suppl+1&rft.issue=&rft.spage=S825&rft.isbn=&rft.btitle=&rft.title=Genetic+epidemiology&rft.issn=07410395&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-15 N1 - Date created - 2002-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adjuvant therapy for breast cancer--results from the USA consensus conference. AN - 72398082; 11791121 AB - The National Institutes of Health, USA sponsored a Consensus Development Conference on November 1-3, 2000 to review several major questions regarding the adjuvant treatment of breast cancer. A non-governmental group of oncology experts was selected to review clinical trial data and judge the evidence presented by 33 breast cancer researchers. Their conclusions resulted in the following recommendations: (1) Prognostic factors critical for determining risk of recurrence are age, axillary lymph node status, tumor size, histologic type and grade and hormone receptor status. (2) Tamoxifen, administered for 5 years, significantly improves long-term survival for women of all age groups with hormone receptor-positive tumors. Ovarian ablation also prolongs survival in premenopausal women. (3) Multi-agent chemotherapy of 4-6 months duration is associated with an improvement in survival in both hormone receptor-positive and -negative tumors. Anthracycline-containing regimens offer the greatest survival advantage. The role of taxanes is uncertain but they may be useful in selected patients with node-positive tumors. Women with small, node-negative tumors, women over age 70, and those with tumors of favorable histologic subtype (mucinous or tubular) may not require chemotherapy. (4) Adjuvant radiotherapy to the regional lymph nodes and chest wall following mastectomy is indicated for women with 4 or more axillary nodes. (5) Physicians should employ effective visual aids to help them present a complete and balanced view of the absolute benefits versus the side-effects of adjuvant treatments. Important avenues of future research were also discussed and suggestions were made. JF - Breast cancer (Tokyo, Japan) AU - Abrams, J S AD - Clinical Investigations Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 6130 Executive Boulevard, EPN 7040, Rockville, MD 20852, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 298 EP - 304 VL - 8 IS - 4 SN - 1340-6868, 1340-6868 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - United States KW - Mastectomy -- methods KW - Randomized Controlled Trials as Topic KW - Disease-Free Survival KW - Drug Administration Schedule KW - Neoplasm Staging KW - Lymphatic Metastasis KW - Humans KW - Quality of Life KW - Aged KW - Tamoxifen -- administration & dosage KW - Survival Rate KW - Adult KW - Tamoxifen -- adverse effects KW - Long-Term Care KW - Middle Aged KW - Physician-Patient Relations KW - Chemotherapy, Adjuvant KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- mortality KW - Breast Neoplasms -- pathology KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents, Hormonal -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72398082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Breast+cancer+%28Tokyo%2C+Japan%29&rft.atitle=Adjuvant+therapy+for+breast+cancer--results+from+the+USA+consensus+conference.&rft.au=Abrams%2C+J+S&rft.aulast=Abrams&rft.aufirst=J&rft.date=2001-01-01&rft.volume=8&rft.issue=4&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+%28Tokyo%2C+Japan%29&rft.issn=13406868&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-07 N1 - Date created - 2002-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in the association of alcohol intoxication and illicit drug abuse among persons arrested for violent and property offenses. AN - 72376623; 11775083 AB - To explore the associations between violent and other crimes, and alcohol intoxication and recent use of cocaine, marijuana, and other drugs among men and women arrestees and examine gender differences in these relationships. We conducted a secondary analysis of 1998 using Arrestee Drug Abuse Monitoring (ADAM) system data using a sample of 9242 male and 2594 women arrested for violent and property offenses in 35 cities. Logistic regression was used to predict arrest for a violent offense (rather than a property crime) from drug- and alcohol-related, and other variables. Both gender and alcohol intoxication are significantly related to arrest for a violent offense. However, the intoxication effects (in the absence of cocaine) are more than three times as great for female (Exp(beta) = 5.59) as male arrestees (Exp(beta) = 1.74), while the combined effects of alcohol and cocaine predict a property offense for women but are insignificant for men. To achieve further reductions in violent crime, intervention strategies need to focus on reducing alcohol intoxication as well as illicit drug use. Research on the role of alcohol on women's aggression and violence also is suggested. JF - Journal of substance abuse AU - Martin, S E AU - Bryant, K AD - National Institute on Alcohol Abuse and Alcoholism, NIH, DHHS, Rockville, MD 20892-7003, USA. smartin@willco.niaaa.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 563 EP - 581 VL - 13 IS - 4 SN - 0899-3289, 0899-3289 KW - Street Drugs KW - 0 KW - Index Medicus KW - Crime KW - Humans KW - Adult KW - Alcoholism -- urine KW - Violence KW - United States -- epidemiology KW - Sex Distribution KW - Male KW - Female KW - Alcoholic Intoxication -- psychology KW - Alcoholic Intoxication -- epidemiology KW - Alcoholic Intoxication -- urine KW - Prisoners -- psychology KW - Street Drugs -- urine KW - Prisoners -- statistics & numerical data KW - Substance Abuse Detection -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72376623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Gender+differences+in+the+association+of+alcohol+intoxication+and+illicit+drug+abuse+among+persons+arrested+for+violent+and+property+offenses.&rft.au=Martin%2C+S+E%3BBryant%2C+K&rft.aulast=Martin&rft.aufirst=S&rft.date=2001-01-01&rft.volume=13&rft.issue=4&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-15 N1 - Date created - 2001-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age at onset of alcohol use and DSM-IV alcohol abuse and dependence: a 12-year follow-up. AN - 72374860; 11775078 AB - The purpose of this study was to examine the relationship between age at drinking onset and the development of DSM-IV alcohol abuse and dependence in a 12-year prospective study of youth in the United States. Logistic regression analyses were used to quantify the relationship between age at drinking onset and the development of alcohol abuse and dependence controlling for sociodemographic factors and problem indicators. The odds of alcohol dependence decreased by 5% in 1989 and 9.0% in 1994 for each year drinking onset was delayed. In 1994, the odds of alcohol abuse increased by 7.0% with each decreasing year of age at drinking onset, while age at drinking onset was not related to alcohol abuse in 1989. Several other risk factors were found to be strong and consistent predictors of abuse and dependence in 1989 and 1994, including being male, divorced, separated or never married, younger, and having an early history antisocial behaviors and marijuana use. Implications of the results of this study are discussed in terms of other factors that may impact on the onset-abuse and onset-dependence relationship and the need to focus future prevention efforts. JF - Journal of substance abuse AU - Grant, B F AU - Stinson, F S AU - Harford, T C AD - Division of Biometry and Epidemiology National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. bg17j@nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 493 EP - 504 VL - 13 IS - 4 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Age Factors KW - Psychiatric Status Rating Scales KW - Age of Onset KW - Humans KW - Health Surveys KW - Adult KW - Predictive Value of Tests KW - Follow-Up Studies KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcohol-Related Disorders -- diagnosis KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcohol Drinking -- epidemiology KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72374860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Age+at+onset+of+alcohol+use+and+DSM-IV+alcohol+abuse+and+dependence%3A+a+12-year+follow-up.&rft.au=Grant%2C+B+F%3BStinson%2C+F+S%3BHarford%2C+T+C&rft.aulast=Grant&rft.aufirst=B&rft.date=2001-01-01&rft.volume=13&rft.issue=4&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-15 N1 - Date created - 2001-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental and host factors in testicular germ cell tumors. AN - 72373080; 11768038 JF - Cancer investigation AU - McGlynn, K A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NCI/DCEG/EEB, Bethesda, Maryland 20893-7234, USA. mcglynnk@mail.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 842 EP - 853 VL - 19 IS - 8 SN - 0735-7907, 0735-7907 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Life Style KW - Cryptorchidism -- complications KW - Environmental Pollutants -- toxicity KW - Risk Factors KW - Humans KW - Endocrine Glands -- drug effects KW - Nutritional Physiological Phenomena KW - Occupations KW - Male KW - Germinoma -- ethnology KW - Germinoma -- etiology KW - Testicular Neoplasms -- etiology KW - Germinoma -- genetics KW - Testicular Neoplasms -- genetics KW - Testicular Neoplasms -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72373080?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=Environmental+and+host+factors+in+testicular+germ+cell+tumors.&rft.au=McGlynn%2C+K+A&rft.aulast=McGlynn&rft.aufirst=K&rft.date=2001-01-01&rft.volume=19&rft.issue=8&rft.spage=842&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-03 N1 - Date created - 2001-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New JC virus (JCV) genotypes from papua new guinea and micronesia (type 8 and type 2E) and evolutionary analysis of 32 complete JCV genomes. AN - 72366959; 11765914 AB - The JC virus (JCV) is a ubiquitous human polyomavirus that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large percentage of the population. Geographic-specific JCV variants, isolated from urine and from brain of progressive multifocal leukoencephalopathy (PML) patients, have been grouped into seven distinct genotypes based on whole genome analysis and by individual polymorphic nucleotides (typing sites) in the VP1 coding region. Mutations in the archetypal regulatory region, sometimes consisting of deletions and/or duplications, are also useful taxonomic characters for further characterizing and subdividing genotypes. Investigation of JCV variation in Papua New Guinea (PNG) revealed three distinct variants called PNG- 1, PNG-2, and PNG-3. These variants exhibited consistent coding region and regulatory region mutations. Evolutionary analysis of 32 complete JCV genomes including six new viral genomes from the western Pacific suggests that the new PNG JCV variants are closely associated with the broad group of Type 2 strains of JCV found throughout Asia, forming a monophyletic group with the Northeast Asian strains (Type 2A). Within the Type 2 clade, however, the PNG JCV variants cluster as two distinct groups and are therefore described here as new JCV genotypes designated Type 2E and Type 8. JF - Archives of virology AU - Jobe, D V AU - Friedlaender, J S AU - Mgone, C S AU - Agostini, H T AU - Koki, G AU - Yanagihara, R AU - Ng TCN AU - Chima, S C AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4126, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 2097 EP - 2113 VL - 146 IS - 11 SN - 0304-8608, 0304-8608 KW - Index Medicus KW - Phylogeny KW - Genotype KW - Polymorphism, Genetic KW - Papua New Guinea KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Genome, Viral KW - Male KW - Female KW - JC Virus -- genetics KW - JC Virus -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72366959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+virology&rft.atitle=New+JC+virus+%28JCV%29+genotypes+from+papua+new+guinea+and+micronesia+%28type+8+and+type+2E%29+and+evolutionary+analysis+of+32+complete+JCV+genomes.&rft.au=Jobe%2C+D+V%3BFriedlaender%2C+J+S%3BMgone%2C+C+S%3BAgostini%2C+H+T%3BKoki%2C+G%3BYanagihara%2C+R%3BNg+TCN%3BChima%2C+S+C%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Jobe&rft.aufirst=D&rft.date=2001-01-01&rft.volume=146&rft.issue=11&rft.spage=2097&rft.isbn=&rft.btitle=&rft.title=Archives+of+virology&rft.issn=03048608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-03 N1 - Date created - 2001-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair and mutagenesis in Werner syndrome. AN - 72356309; 11746759 AB - Werner syndrome (WS) is the hallmark premature aging syndrome in which the patients appear much older than their actual chronological age. The disorder is associated with significantly increased genome instability and with transcriptional deficiencies. There has been some uncertainty about whether WS cells are defective in DNA repair. We thus examined repair in vitro in nuclear and mitochondrial DNA. Whereas cellular studies so far do not show significant DNA repair deficiencies, biochemical studies with the Werner protein clearly indicate that it plays a role in DNA repair. JF - Environmental and molecular mutagenesis AU - Bohr, V A AU - Souza Pinto, N AU - Nyaga, S G AU - Dianov, G AU - Kraemer, K AU - Seidman, M M AU - Brosh, R M AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. vbohr@nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 227 EP - 234 VL - 38 IS - 2-3 SN - 0893-6692, 0893-6692 KW - DNA, Mitochondrial KW - 0 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - Humans KW - DNA Helicases -- genetics KW - Cell Line KW - DNA, Mitochondrial -- genetics KW - DNA Repair KW - Werner Syndrome -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72356309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=DNA+repair+and+mutagenesis+in+Werner+syndrome.&rft.au=Bohr%2C+V+A%3BSouza+Pinto%2C+N%3BNyaga%2C+S+G%3BDianov%2C+G%3BKraemer%2C+K%3BSeidman%2C+M+M%3BBrosh%2C+R+M&rft.aulast=Bohr&rft.aufirst=V&rft.date=2001-01-01&rft.volume=38&rft.issue=2-3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-09 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-mediated apoptosis and genomic instability diseases. AN - 72355559; 11765063 AB - Mutations in several DExH-containing DNA helicases, including XPD, XPB, WRN, and BLM, are associated with rare familial cancer syndromes characterized by genomic instability and cancer susceptibility. Known cellular activities of these helicases include DNA replication, repair, recombination, and/or transcription. The p53 tumor suppressor is a regulator of cellular responses to stress, and is biochemically involved in the induction of cell-cycle arrest, apoptosis and DNA repair, all of which contribute to maintenance of genomic integrity. Physical and functional interactions of p53 with DExH-containing DNA helicases have been described. We propose that such interactions could be compromised in inherited disorders and contribute to their cancer susceptibility. In particular, the role of DNA helicases in p53-mediated apoptotic pathways is reviewed. JF - Acta oncologica (Stockholm, Sweden) AU - Robles, A I AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 696 EP - 701 VL - 40 IS - 6 SN - 0284-186X, 0284-186X KW - Tumor Suppressor Protein p53 KW - 0 KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - DNA Damage KW - Humans KW - Cell Cycle KW - Tumor Suppressor Protein p53 -- biosynthesis KW - DNA Repair KW - Apoptosis KW - DNA Helicases -- metabolism KW - Neoplasms -- physiopathology KW - Genetic Predisposition to Disease KW - Tumor Suppressor Protein p53 -- pharmacology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72355559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=p53-mediated+apoptosis+and+genomic+instability+diseases.&rft.au=Robles%2C+A+I%3BHarris%2C+C+C&rft.aulast=Robles&rft.aufirst=A&rft.date=2001-01-01&rft.volume=40&rft.issue=6&rft.spage=696&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-28 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic factors involved in central nervous system/immune interactions. AN - 72313635; 11727781 AB - Analysis of several inbred rat strains has led us to hypothesize that HPA axis abnormalities may contribute, in part, to susceptibility to both autoimmune disease and addiction. In this article we review the evidence for this hypothesis and describe our ongoing efforts to genetically characterize these traits. We have mapped the locations of 23 loci that regulate autoimmune disease in rats, and are currently constructing QTL congenic lines in which a genomic region from the resistant strain is transferred to the susceptible strain or vice versa. These QTL congenic lines will be valuable to test whether genes encoding autoimmune regulation also control neuroendocrine traits. Further genetic dissection and identification of the underlying genes will be necessary to infer a mechanistic link between autoimmune and neuroendocrine traits. JF - Advances in experimental medicine and biology AU - Wilder, R L AU - Griffiths, M M AU - Cannon, G W AU - Caspi, R AU - Gulko, P S AU - Remmers, E F AD - Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 59 EP - 67 VL - 493 SN - 0065-2598, 0065-2598 KW - Narcotics KW - 0 KW - Opioid Peptides KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Quantitative Trait, Heritable KW - Autoimmune Diseases -- genetics KW - Animals KW - Opioid Peptides -- physiology KW - Models, Genetic KW - Humans KW - Narcotics -- toxicity KW - Drug Resistance KW - Animals, Congenic KW - Models, Neurological KW - Substance-Related Disorders -- genetics KW - Pituitary-Adrenal System -- immunology KW - Hypothalamo-Hypophyseal System -- immunology KW - Neuroimmunomodulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72313635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Genetic+factors+involved+in+central+nervous+system%2Fimmune+interactions.&rft.au=Wilder%2C+R+L%3BGriffiths%2C+M+M%3BCannon%2C+G+W%3BCaspi%2C+R%3BGulko%2C+P+S%3BRemmers%2C+E+F&rft.aulast=Wilder&rft.aufirst=R&rft.date=2001-01-01&rft.volume=493&rft.issue=&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-20 N1 - Date created - 2001-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of effect of moderate Purkinje cell loss on working memory. AN - 72292359; 11718998 AB - 192 immunoglobulin G-saporin (192-sap) is an immunotoxin which targets the cholinergic basal forebrain after injection into either the ventricular system or the parenchyma of the rat brain. When injected by the i.c.v. route, 192-sap kills some cerebellar Purkinje cells in addition to its more extensive killing of the cholinergic basal forebrain. Behaviorally, i.c.v. injections of 192-sap result in impaired performance in a variety of experimental paradigms of learning and memory including a working memory task in the radial maze. The current study examined the contribution, if any, of immunotoxin-induced Purkinje cell loss to impaired performance in the radial maze. To meet this aim, we used i.c.v. injection of another immunotoxin, OX7-saporin (OX7-sap), at a dose that produced Purkinje cell loss of similar extent to that produced by i.c.v. 192-sap. We then compared these OX7-sap-injected rats with 192-sap-injected rats in a radial maze working memory task. We found a working memory impairment only in the 192-sap-injected rats. These data show that moderate Purkinje cell loss alone is insufficient to impair working memory. Furthermore, the data are consistent with the idea that the working memory deficit observed in 192-sap-injected animals is likely due to lesioning of the cholinergic basal forebrain. JF - Neuroscience AU - Wrenn, C C AU - Wiley, R G AD - Laboratory of Experimental Neurology, Veterans Administration Medical Center, Nashville, TN 37212, USA. wrennc@intra.nimh.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 433 EP - 445 VL - 107 IS - 3 SN - 0306-4522, 0306-4522 KW - Antibodies, Monoclonal KW - 0 KW - Immunoconjugates KW - Immunotoxins KW - OX7-saporin KW - Ribosome Inactivating Proteins, Type 1 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - Index Medicus KW - Animals KW - Maze Learning -- physiology KW - Neurons -- drug effects KW - Cholinergic Fibers -- physiology KW - Rats, Inbred BN KW - Rats KW - Choice Behavior -- drug effects KW - Prosencephalon -- physiology KW - Immunotoxins -- pharmacology KW - Injections KW - Memory -- physiology KW - Purkinje Cells -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72292359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Lack+of+effect+of+moderate+Purkinje+cell+loss+on+working+memory.&rft.au=Wrenn%2C+C+C%3BWiley%2C+R+G&rft.aulast=Wrenn&rft.aufirst=C&rft.date=2001-01-01&rft.volume=107&rft.issue=3&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-15 N1 - Date created - 2001-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine. AN - 72276033; 11705118 JF - The Alkaloids. Chemistry and biology AU - Baumann, M H AU - Pablo, J AU - Ali, S F AU - Rothman, R B AU - Mash, D C AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 79 EP - 113 VL - 56 SN - 1099-4831, 1099-4831 KW - noribogaine KW - 0 KW - Serotonin KW - 333DO1RDJY KW - Ibogaine KW - 3S814I130U KW - Dopamine KW - VTD58H1Z2X KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Serotonin -- physiology KW - Corticosterone -- blood KW - Humans KW - Brain -- drug effects KW - Dopamine -- physiology KW - Opioid-Related Disorders -- drug therapy KW - Ibogaine -- toxicity KW - Ibogaine -- analogs & derivatives KW - Ibogaine -- pharmacology KW - Ibogaine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72276033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Alkaloids.+Chemistry+and+biology&rft.atitle=Comparative+neuropharmacology+of+ibogaine+and+its+O-desmethyl+metabolite%2C+noribogaine.&rft.au=Baumann%2C+M+H%3BPablo%2C+J%3BAli%2C+S+F%3BRothman%2C+R+B%3BMash%2C+D+C&rft.aulast=Baumann&rft.aufirst=M&rft.date=2001-01-01&rft.volume=56&rft.issue=&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=The+Alkaloids.+Chemistry+and+biology&rft.issn=10994831&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tg.AC genetically altered mouse: assay working group overview of available data. AN - 72252657; 11695563 AB - In a Government/Industry/Academic partnership to evaluate alternative approaches to carcinogenicity testing, 21 pharmaceutical agents representing a variety of chemical and pharmacological classes and possessing known human and or rodent carcinogenic potential were selected for study in several rodent models. The studies from this partnership project, coordinated by the International Life Sciences Institute, provide additional data to better understand the models' limitations and sensitivity in identifying carcinogens. The results of these alternative model studies were reviewed by members of Assay Working Groups (AWG) composed of scientists from government and industry with expertise in toxicology, genetics, statistics, and pathology. The Tg.AC genetically manipulated mouse was one of the models selected for this project based on previous studies indicating that Tg.AC mice seem to respond to topical application of either mutagenic or nonmutagenic carcinogens with papilloma formation at the site of application. This communication describes the results and AWG interpretations of studies conducted on 14 chemicals administered by the topical and oral (gavage and/or diet) routes to Tg.AC genetically manipulated mice. Cyclosporin A, an immunosuppresant human carcinogen, ethinyl estradiol and diethylstilbestrol (human hormone carcinogens) and clofibrate, an hepatocarcinogenic peroxisome proliferator in rodents, were considered clearly positive in the topical studies. In the oral studies, ethinyl estradiol and diethylstilbestrol were negative, cyclosporin was considered equivocal, and results were not available for the clofibrate study. Of the 3 genotoxic human carcinogens (phenacetin, melphalan, and cyclophosphamide), phenacetin was negative by both the topical and oral routes. Melphalan and cyclophosphamide are, respectively, direct and indirect DNA alkylating agents and topical administration of both caused equivocal responses. With the exception of clofibrate, Tg.AC mice did not exhibit tumor responses to the rodent carcinogens that were putative human noncarcinogens, (di(2-ethylhexyl) phthalate, methapyraline HCl, phenobarbital Na, reserpine, sulfamethoxazole or WY-14643, or the nongenotoxic, noncarcinogen, sulfisoxazole) regardless of route of administration. Based on the observed responses in these studies, it was concluded by the AWG that the Tg.AC model was not overly sensitive and possesses utility as an adjunct to the battery of toxicity studies used to establish human carcinogenic risk. JF - Toxicologic pathology AU - Eastin, W C AU - Mennear, J H AU - Tennant, R W AU - Stoll, R E AU - Branstetter, D G AU - Bucher, J R AU - McCullough, B AU - Binder, R L AU - Spalding, J W AU - Mahler, J F AD - National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27713-2233, USA. eastin@niehs.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 60 EP - 80 VL - 29 Suppl SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Genotype KW - Animals KW - Animal Testing Alternatives KW - Reproducibility of Results KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Male KW - Female KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Papilloma -- pathology KW - Skin Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Skin Neoplasms -- pathology KW - Papilloma -- genetics KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72252657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Tg.AC+genetically+altered+mouse%3A+assay+working+group+overview+of+available+data.&rft.au=Eastin%2C+W+C%3BMennear%2C+J+H%3BTennant%2C+R+W%3BStoll%2C+R+E%3BBranstetter%2C+D+G%3BBucher%2C+J+R%3BMcCullough%2C+B%3BBinder%2C+R+L%3BSpalding%2C+J+W%3BMahler%2C+J+F&rft.aulast=Eastin&rft.aufirst=W&rft.date=2001-01-01&rft.volume=29+Suppl&rft.issue=&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-21 N1 - Date created - 2001-11-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The Tg.AC (v-Ha-ras) transgenic mouse: nature of the model. AN - 72252619; 11695562 AB - The Tg.AC (v-Ha-ras) transgenic mouse model provides a reporter phenotype of skin papillomas in response to either genotoxic or nongenotoxic carcinogens. In common with the conventional bioassay, the Tg.AC model responds to known human carcinogens and does not respond to noncarcinogens. It also does not respond to most chemicals that are positive in conventional bioassays principally at sites of high spontaneous tumor incidence. The mechanism of response of the Tg.AC model is related to the structure and genomic position of the transgene and the induction of transgene expression through specific mediated interactions between the chemicals and target cells in the skin. JF - Toxicologic pathology AU - Tennant, R W AU - Stasiewicz, S AU - Eastin, W C AU - Mennear, J H AU - Spalding, J W AD - National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709, USA. tennant@niehs.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 51 EP - 59 VL - 29 Suppl SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animal Testing Alternatives KW - Animals KW - Carcinogens -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Societies, Scientific KW - Academies and Institutes KW - Carcinogens -- toxicity KW - Mice KW - Mice, Transgenic KW - Administration, Topical KW - Female KW - Male KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Papilloma -- pathology KW - Skin Neoplasms -- chemically induced KW - Carcinogenicity Tests -- methods KW - Skin Neoplasms -- pathology KW - Disease Models, Animal KW - Papilloma -- genetics KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72252619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+Tg.AC+%28v-Ha-ras%29+transgenic+mouse%3A+nature+of+the+model.&rft.au=Tennant%2C+R+W%3BStasiewicz%2C+S%3BEastin%2C+W+C%3BMennear%2C+J+H%3BSpalding%2C+J+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=2001-01-01&rft.volume=29+Suppl&rft.issue=&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-21 N1 - Date created - 2001-11-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The nature of the heterozygous Trp53 knockout model for identification of mutagenic carcinogens. AN - 72251776; 11695559 AB - The heterozygous Trp53 null allele C57BL/6 (N5) mouse is susceptible to the rapid development of neoplasia by mutagenic carcinogens relative to control strains. This mouse model of chemical carcinogenesis demonstrates 1) dose-related rapid induction of tumors (26 wks), 2) multiple sites of carcinogen-specific tissue susceptibility, and 3) carcinogen-induced loss of heterozygosity involving the Trp53 wild-type allele or a p53 haploinsufficiency permitting mutation of other critical protooncogenes and/or inactivation of tumor suppressor genes driving tumorigenesis. Demonstration of mutation or loss of heterozygosity involving the Trp53 locus is consistent with a common finding in human cancers and supports extrapolation between rodents and humans. Using diverse experimental protocols, almost all mutagenic rodent carcinogens (including all mutagens that are carcinogenic to humans), but not nonmutagenic rodent carcinogens, induce tumors within 26 weeks of continuous exposure. These characteristics and results indicate that the mouse heterozygous for the Trp53 null allele may be of significant use for the prospective identification of mutagenic carcinogens of potential risk to human health. JF - Toxicologic pathology AU - French, J AU - Storer, R D AU - Donehower, L A AD - National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 24 EP - 29 VL - 29 Suppl SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Loss of Heterozygosity KW - Heterozygote KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Female KW - Risk Assessment KW - Mice, Knockout KW - Genes, p53 KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mutagens -- toxicity KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72251776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+nature+of+the+heterozygous+Trp53+knockout+model+for+identification+of+mutagenic+carcinogens.&rft.au=French%2C+J%3BStorer%2C+R+D%3BDonehower%2C+L+A&rft.aulast=French&rft.aufirst=J&rft.date=2001-01-01&rft.volume=29+Suppl&rft.issue=&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-21 N1 - Date created - 2001-11-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The 5-year course of alcohol abuse among young adults. AN - 72248186; 11693449 AB - This study describes the course of alcohol abuse among a nationally representative sample of young adults over a 5-year time period for the purpose of examining the validity of the DSM-IV alcohol abuse category. DSM-IV diagnoses of alcohol abuse at baseline and follow-up were examined using logistic regression analyses. Alcohol abuse and dependence were shown to have different courses. Very few abusers at Time 1 became dependent at Time 2, suggesting that abuse is not merely prodromal to dependence. Females, Blacks, and high school dropouts were less likely to receive an abuse diagnosis at baseline. Marital status, family history, earlier onset of drinking, and heavy drinking were also related to abuse at baseline. Alcohol abuse at baseline, in addition to gender, marital status, family history, early onset drinking, and heavy drinking, predicted abuse at follow-up. Exclusion of the hazardous criterion item "driving after drinking too much" from the abuse diagnosis yielded similar results. The DSM-IV alcohol abuse category was shown to have some diagnostic utility. JF - Journal of substance abuse AU - Grant, B F AU - Stinson, F S AU - Harford, T AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. bg17j@nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 229 EP - 238 VL - 13 IS - 3 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Regression Analysis KW - Reproducibility of Results KW - Risk Factors KW - Humans KW - Adult KW - Follow-Up Studies KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Time Factors KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcoholism -- classification KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72248186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=The+5-year+course+of+alcohol+abuse+among+young+adults.&rft.au=Grant%2C+B+F%3BStinson%2C+F+S%3BHarford%2C+T&rft.aulast=Grant&rft.aufirst=B&rft.date=2001-01-01&rft.volume=13&rft.issue=3&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship of early-onset regular smoking to alcohol use, depression, illicit drug use, and other risky behaviors during early adolescence: results from the youth supplement to the third national health and nutrition examination survey. AN - 72245897; 11693451 AB - Recently we found that the early onset of regular tobacco use is as predictive of lifetime drug use and depressive disorders as it is of alcohol use disorders [Alcohol.: Clin. Exp. Res. 23 (1999) 513.]. This finding, which paralleled findings regarding early onset of alcohol use [J. Subst. Abuse 10 (1998) 59.], suggested that early regular use of any drug might simply be an indicator of risk for a constellation of problem behaviors. The purpose of the present study is to test this hypothesis as well as to study the strength and patterns of associations among these problem behaviors already present among youth. The results will permit description of more precise profiles to identify groups of children at risk. Using data for respondents aged 12-16 from the Third National Health and Nutrition Examination Survey (NHANES III), descriptive statistics were calculated and logistic regression models were estimated. Descriptive analyses indicated that in comparison with those who never smoked, or who simply experimented, early-onset regular smokers, both those who began at age 13 or younger and those who did so between 14 and 16, were those most likely to use alcohol and other drugs as well as have school problems and early sexual experiences culminating in pregnancy. Multivariate logistic regression analyses were conducted to assess the associations among these high-risk behaviors. These results support the hypothesis that early onset of smoking is but an indicator of a syndrome of problem behaviors already in place during childhood. They also suggest that the significance of an age onset variable may differ depending on the age of the sample used. As follow-up data are collected, we expect to learn much about the natural course of the distinct risk groups identified in the analyses by studying longitudinally this nationally representative group of early adolescents. JF - Journal of substance abuse AU - Hanna, E Z AU - Yi, H Y AU - Dufour, M C AU - Whitmore, C C AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. ehanna@willco.niaaa.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 265 EP - 282 VL - 13 IS - 3 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - United States KW - Age Factors KW - Risk-Taking KW - Age of Onset KW - Humans KW - Child KW - Multivariate Analysis KW - Pregnancy KW - Adaptation, Psychological KW - Logistic Models KW - Adolescent Behavior -- psychology KW - Surveys and Questionnaires KW - Adolescent KW - Female KW - Male KW - Depressive Disorder -- psychology KW - Health Surveys KW - Alcohol Drinking -- psychology KW - Alcohol Drinking -- prevention & control KW - Smoking -- psychology KW - Smoking -- prevention & control KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72245897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=The+relationship+of+early-onset+regular+smoking+to+alcohol+use%2C+depression%2C+illicit+drug+use%2C+and+other+risky+behaviors+during+early+adolescence%3A+results+from+the+youth+supplement+to+the+third+national+health+and+nutrition+examination+survey.&rft.au=Hanna%2C+E+Z%3BYi%2C+H+Y%3BDufour%2C+M+C%3BWhitmore%2C+C+C&rft.aulast=Hanna&rft.aufirst=E&rft.date=2001-01-01&rft.volume=13&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppressor and oncogenic roles of transforming growth factor-beta and its signaling pathways in tumorigenesis. AN - 72218764; 11665716 AB - Transforming growth factor-beta (TGF-beta) has been implicated in oncogenesis since the time of its discovery almost 20 years ago. The complex, multifunctional activities of TGF-beta endow it with both tumor suppressor and tumor promoting activities, depending on the stage of carcinogenesis and the responsivity of the tumor cell. Dysregulation or alteration of TGF-beta signaling in tumorigenesis can occur at many different levels, including activation of the ligand, mutation or transcriptional suppression of the receptors, or alteration of downstream signal transduction pathways resulting from mutation or changes in expression patterns of signaling intermediates or from changes in expression of other proteins which modulate signaling. New insights into signaling from the TGF-beta receptors, including the identification of Smad signaling pathways and their interaction with mitogen-activated protein (MAP) kinase pathways, are providing an understanding of the changes involved in the change from tumor suppressor to tumor promoting activities of TGF-beta. It is now appreciated that loss of sensitivity to inhibition of growth by TGF-beta by most tumor cells is not synonymous with complete loss of TGF-beta signaling but rather suggests that tumor cells gain advantage by selective inactivation of the tumor suppressor activities of TGF-beta with retention of its tumor promoting activities, especially those dependent on cross talk with MAP kinase pathways and AP-1. JF - Advances in cancer research AU - Piek, E AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-8395, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 1 EP - 54 VL - 83 SN - 0065-230X, 0065-230X KW - Protein Isoforms KW - 0 KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Genes, Tumor Suppressor KW - Humans KW - Cell Differentiation KW - Mutation KW - Models, Biological KW - Signal Transduction KW - Transforming Growth Factor beta -- physiology KW - Transforming Growth Factor beta -- chemistry KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72218764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+cancer+research&rft.atitle=Suppressor+and+oncogenic+roles+of+transforming+growth+factor-beta+and+its+signaling+pathways+in+tumorigenesis.&rft.au=Piek%2C+E%3BRoberts%2C+A+B&rft.aulast=Piek&rft.aufirst=E&rft.date=2001-01-01&rft.volume=83&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Advances+in+cancer+research&rft.issn=0065230X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-11 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neoadjuvant chemotherapy plus conventional radiotherapy or accelerated hyperfractionation in stage III and IV nasopharyngeal carcinoma--a phase II study. AN - 72218700; 11669328 AB - A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal carcinoma (NPC). The goal was to achieve improvement in locoregional control, disease-free interval and overall survival using induction chemotherapy and to compare conventional fractionation (CF) with an accelerated hyperfractionation (AHF) regimen. Fifty patients were treated (5 AJCC Stage III, 45 Stage IV) with induction chemotherapy consisting of two cycles of cisplatin and 5-fluorouracil. Patients were then randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86% of patients prior to radiotherapy (44% complete response, 42% partial response). Patients with complete or major partial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and disease-free interval (59%) than those with no response or minor partial response (15% and 18% p = 0.009 and 0.0009). Acute radiation reactions were more pronounced in the AHF group (p = 0.0002), and the incidence of late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.52; 95%, Cl, 0.15-2.83; p = 0.186). With a median follow-up period of 55 months (range 4-120), the 5-year disease-free interval and overall survival rates were more favorable in the AHF group than in the CF group, but the differences were not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval = 0.71; 95% CI, 0.27-1.88; p=0.198 and HR for overall survival = 0.81; 95% CI, 0.37-1.78; p=0.433). The overall treatment failure rate was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached 30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval and overall survival. Accelerated hyperfractionation was associated with high incidence of acute and late toxicity without significant improvement in locoregional control rate. The optimal chemotherapy dose and sequencing with radiotherapy needs to be investigated in future studies. Distant metastases remain the main cause of treatment failure in NPC. JF - Acta oncologica (Stockholm, Sweden) AU - El-Weshi, A AU - Khafaga, Y AU - Allam, A AU - Mosseri, V AU - Ibrahim, E AU - El-Serafi, M AU - El-Badawi, S AD - Department of Medical Oncology, National Cancer Institute of Cairo, Egypt. elweshiamr@yahoo.com Y1 - 2001 PY - 2001 DA - 2001 SP - 574 EP - 581 VL - 40 IS - 5 SN - 0284-186X, 0284-186X KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Aged KW - Fluorouracil -- therapeutic use KW - Cisplatin -- therapeutic use KW - Fluorouracil -- adverse effects KW - Life Tables KW - Prospective Studies KW - Adult KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Cisplatin -- adverse effects KW - Adolescent KW - Female KW - Male KW - Survival Analysis KW - Radiation Injuries -- etiology KW - Nasopharyngeal Neoplasms -- radiotherapy KW - Nasopharyngeal Neoplasms -- mortality KW - Dose Fractionation KW - Carcinoma -- radiotherapy KW - Carcinoma, Squamous Cell -- mortality KW - Radioisotope Teletherapy -- methods KW - Radioisotope Teletherapy -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Chemotherapy, Adjuvant -- adverse effects KW - Nasopharyngeal Neoplasms -- drug therapy KW - Carcinoma -- pathology KW - Carcinoma, Squamous Cell -- pathology KW - Carcinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma -- mortality KW - Carcinoma, Squamous Cell -- drug therapy KW - Carcinoma, Squamous Cell -- radiotherapy KW - Nasopharyngeal Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72218700?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Addiction+Research&rft.atitle=%22Eyes+Wide+Shut%3F--A+Conceptual+and+Empirical+Critique+of+Methadone+Maintenance+Treatment%22%3A+Comment&rft.au=Newman%2C+Robert+G.&rft.aulast=Newman&rft.aufirst=Robert&rft.date=2005-03-01&rft.volume=11&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=European+Addiction+Research&rft.issn=10226877&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The origin of radiophobias. AN - 72201751; 11600800 JF - Perspectives in biology and medicine AU - Myslobodsky, M AD - College of Arts and Sciences, Howard University, Washington, DC 20059, USA. myslobom@codon.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 543 EP - 555 VL - 44 IS - 4 SN - 0031-5982, 0031-5982 KW - Index Medicus KW - United States KW - Radiation Dosage KW - Neoplasms, Radiation-Induced -- etiology KW - Occupational Exposure -- standards KW - Fear KW - Humans KW - Ethics KW - Interpersonal Relations KW - Social Responsibility KW - Radiation, Ionizing KW - Environmental Exposure -- standards KW - Radiation Protection -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72201751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Perspectives+in+biology+and+medicine&rft.atitle=The+origin+of+radiophobias.&rft.au=Myslobodsky%2C+M&rft.aulast=Myslobodsky&rft.aufirst=M&rft.date=2001-01-01&rft.volume=44&rft.issue=4&rft.spage=543&rft.isbn=&rft.btitle=&rft.title=Perspectives+in+biology+and+medicine&rft.issn=00315982&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic uses of non-steroidal anti-inflammatory drugs in dentistry. AN - 72197827; 11603504 AB - The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing. JF - Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists AU - Dionne, R A AU - Berthold, C W AD - Pain & Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892-1258, USA. rdionne@dir.nidcr.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 315 EP - 330 VL - 12 IS - 4 SN - 1045-4411, 1045-4411 KW - Analgesics, Opioid KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Drug Combinations KW - Isoenzymes KW - Membrane Proteins KW - beta-Endorphin KW - 60617-12-1 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Ketorolac KW - YZI5105V0L KW - Dentistry KW - Index Medicus KW - Humans KW - Periodontitis -- drug therapy KW - beta-Endorphin -- blood KW - Edema -- drug therapy KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Isoenzymes -- antagonists & inhibitors KW - Analgesics, Opioid -- therapeutic use KW - Ketorolac -- therapeutic use KW - Temporomandibular Joint Disorders -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Toothache -- drug therapy KW - Facial Pain -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72197827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oral+biology+and+medicine+%3A+an+official+publication+of+the+American+Association+of+Oral+Biologists&rft.atitle=Therapeutic+uses+of+non-steroidal+anti-inflammatory+drugs+in+dentistry.&rft.au=Dionne%2C+R+A%3BBerthold%2C+C+W&rft.aulast=Dionne&rft.aufirst=R&rft.date=2001-01-01&rft.volume=12&rft.issue=4&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oral+biology+and+medicine+%3A+an+official+publication+of+the+American+Association+of+Oral+Biologists&rft.issn=10454411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroleptic effects on autonomic activity in schizophrenia: between-group and within-subject paradigms and comparisons with controls. AN - 72189615; 11596851 AB - Effects of fluphenazine on electrodermal activity (EDA) and heart rate (HR) were studied in patients with schizophrenia and normal control subjects during rest periods, presentation of innocuous tones, and a reaction time (RT) task. Two types of analyses were used: (1) between-group analyses-patients taking placebo were compared with patients taking fluphenazine and with control subjects using only data from the first test session; and (2) within-subject analyses-the same patients were tested when taking fluphenazine and when taking placebo. Results showed higher resting EDA and HR and smaller increments to task performance in placebo patients than in control subjects. Fluphenazine attenuated EDA levels but not the tonic response. Fluphenazine attenuated the HR response but did not affect HR level. Placebo patients were electrodermally hyporesponsive to the RT stimuli but not to simple tones. Fluphenazine markedly attenuated responsivity to simple tones but it attenuated responsivity less for RT stimuli. Testing medicated patients may thus produce misleading results with respect to many, but not all, purported autonomic markers of diagnosis in schizophrenia studies. JF - Schizophrenia bulletin AU - Zahn, T P AU - Pickar, D AU - van Kammen, D P AD - Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1366, USA. tpz@mail.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 503 EP - 515 VL - 27 IS - 3 SN - 0586-7614, 0586-7614 KW - Antiparkinson Agents KW - 0 KW - Antipsychotic Agents KW - Benztropine KW - 1NHL2J4X8K KW - Fluphenazine KW - S79426A41Z KW - Index Medicus KW - Reaction Time -- drug effects KW - Humans KW - Electrocardiography KW - Parkinsonian Disorders -- chemically induced KW - Adult KW - Antiparkinson Agents -- therapeutic use KW - Benztropine -- therapeutic use KW - Parkinsonian Disorders -- drug therapy KW - Male KW - Female KW - Heart Rate -- drug effects KW - Fluphenazine -- pharmacology KW - Fluphenazine -- adverse effects KW - Antipsychotic Agents -- therapeutic use KW - Antipsychotic Agents -- pharmacology KW - Fluphenazine -- therapeutic use KW - Schizophrenia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72189615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+bulletin&rft.atitle=Neuroleptic+effects+on+autonomic+activity+in+schizophrenia%3A+between-group+and+within-subject+paradigms+and+comparisons+with+controls.&rft.au=Zahn%2C+T+P%3BPickar%2C+D%3Bvan+Kammen%2C+D+P&rft.aulast=Zahn&rft.aufirst=T&rft.date=2001-01-01&rft.volume=27&rft.issue=3&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+bulletin&rft.issn=05867614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-07 N1 - Date created - 2001-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene-environment interrelations in prostate cancer. AN - 72185624; 11588843 JF - Epidemiologic reviews AU - Hayes, R B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. hayesr@mail.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 163 EP - 167 VL - 23 IS - 1 SN - 0193-936X, 0193-936X KW - Index Medicus KW - Polymorphism, Genetic KW - Molecular Epidemiology KW - Epidemiologic Studies KW - Humans KW - Male KW - Prostatic Neoplasms -- epidemiology KW - Cocarcinogenesis KW - Prostatic Neoplasms -- genetics KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72185624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologic+reviews&rft.atitle=Gene-environment+interrelations+in+prostate+cancer.&rft.au=Hayes%2C+R+B&rft.aulast=Hayes&rft.aufirst=R&rft.date=2001-01-01&rft.volume=23&rft.issue=1&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Epidemiologic+reviews&rft.issn=0193936X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-23 N1 - Date created - 2001-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease. AN - 72182425; 11591460 AB - Huntington's disease is a progressive, inherited neurodegenerative disorder characterized by the loss of subsets of neurons primarily in the striatum. In this study, we assessed the neuroprotective effect of lithium against striatal lesion formation in a rat model of Huntington's disease in which quinolinic acid was unilaterally infused into the striatum. For this purpose, we used a dopamine receptor autoradiography and glutamic acid decarboxylase mRNA in situ hybridization analysis, methods previously shown to be adequate for quantitative analysis of the excitotoxin-induced striatal lesion size. Here we demonstrated that subcutaneous injections of LiCl for 16 days prior to quinolinic acid infusion considerably reduced the size of quinolinic acid-induced striatal lesion. Furthermore, these lithium pre-treatments also decreased the number of striatal neurons labeled with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Immunohistochemistry and western blotting demonstrated that lithium-elicited neuroprotection was associated with an increase in Bcl-2 protein levels. Our results raise the possibility that lithium may be considered as a neuroprotective agent in treatment of neurodegenerative diseases such as Huntington's disease. JF - Neuroscience AU - Wei, H AU - Qin, Z H AU - Senatorov, V V AU - Wei, W AU - Wang, Y AU - Qian, Y AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1363, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 603 EP - 612 VL - 106 IS - 3 SN - 0306-4522, 0306-4522 KW - Antimanic Agents KW - 0 KW - Benzazepines KW - Dopamine Antagonists KW - Isoenzymes KW - Neuroprotective Agents KW - Neurotoxins KW - RNA, Messenger KW - Receptors, Dopamine D1 KW - Cyclin D1 KW - 136601-57-5 KW - Lithium KW - 9FN79X2M3F KW - Glutamate Decarboxylase KW - EC 4.1.1.15 KW - glutamate decarboxylase 1 KW - Quinolinic Acid KW - F6F0HK1URN KW - Lithium Chloride KW - G4962QA067 KW - Index Medicus KW - Animals KW - Antimanic Agents -- pharmacology KW - RNA, Messenger -- drug effects KW - Glutamate Decarboxylase -- genetics KW - Quinolinic Acid -- pharmacology KW - Cyclin D1 -- drug effects KW - Disease Models, Animal KW - Receptors, Dopamine D1 -- drug effects KW - Radioligand Assay KW - Isoenzymes -- genetics KW - Receptors, Dopamine D1 -- metabolism KW - Rats KW - In Situ Nick-End Labeling KW - Rats, Sprague-Dawley KW - Cyclin D1 -- metabolism KW - RNA, Messenger -- metabolism KW - Dopamine Antagonists -- pharmacokinetics KW - Lithium Chloride -- pharmacology KW - Immunohistochemistry KW - Male KW - Benzazepines -- pharmacokinetics KW - Cell Death -- physiology KW - Neurons -- metabolism KW - Huntington Disease -- chemically induced KW - Neurons -- drug effects KW - Huntington Disease -- drug therapy KW - Cell Death -- drug effects KW - Neostriatum -- physiopathology KW - Neurotoxins -- antagonists & inhibitors KW - Neuroprotective Agents -- pharmacology KW - Neurons -- pathology KW - Neostriatum -- drug effects KW - Neostriatum -- pathology KW - Huntington Disease -- pathology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72182425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Lithium+suppresses+excitotoxicity-induced+striatal+lesions+in+a+rat+model+of+Huntington%27s+disease.&rft.au=Wei%2C+H%3BQin%2C+Z+H%3BSenatorov%2C+V+V%3BWei%2C+W%3BWang%2C+Y%3BQian%2C+Y%3BChuang%2C+D+M&rft.aulast=Wei&rft.aufirst=H&rft.date=2001-01-01&rft.volume=106&rft.issue=3&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emerging role of drug interaction studies in drug development: the good, the bad, and the unknown. AN - 71334372; 12397858 AB - Significant scientific advancements in the last decade have armed researchers with tools to assess drug metabolism and the effects of drugs on metabolic pathways; however, most of this research has focused on cytochrome P450 isozymes. Early delineation of this information aids in the prediction of potential drug-drug interactions, which may ultimately determine whether a compound is pursued in the drug development process. The recent withdrawals of medications such as terfenadine, astemizole, cisapride, and mibefradil from the market demonstrate the relevance of this a priori approach--the risk of drug interactions was largely unrecognized prior to their approval by the Food and Drug Administration (FDA). Drug interaction studies for new drug applications (NDAs) field between 1987 and 1991 were largely in vivo studies with potential coadministered drugs, whereas for NDAs field between 1992 and 1997, the majority of studies involved metabolic mechanisms and in vitro methodology. Despite current limitations in the extrapolation of in vitro drug metabolism data to the in vivo environment, in vitro studies remain the mainstay of initial evaluations in this area primarily because of the high throughput nature of these investigations and the reduced cost compared with in vivo studies. The FDA has published several guidance documents in the area of drug metabolism and drug interaction studies in drug development with suggestions for in vitro as well as in vivo approaches to these investigations. Current and future research will likely focus on in vitro models for cytochrome P450 induction, Phase II metabolism, and drug transporters, and include validation and extrapolation of these approaches in vivo. JF - Psychopharmacology bulletin AU - Alfaro, C L AD - National Institutes of Health Clinical Center Pharmacy Department, 10 Center Drive, Building 10, Room 1N257, Bethesda, MD 20892, USA. calfaro@nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 80 EP - 93 VL - 35 IS - 4 SN - 0048-5764, 0048-5764 KW - Isoenzymes KW - 0 KW - Pharmaceutical Preparations KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - United States KW - Pharmaceutical Preparations -- metabolism KW - United States Food and Drug Administration KW - Humans KW - Isoenzymes -- metabolism KW - Pharmacology, Clinical -- trends KW - Drug Interactions KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71334372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology+bulletin&rft.atitle=Emerging+role+of+drug+interaction+studies+in+drug+development%3A+the+good%2C+the+bad%2C+and+the+unknown.&rft.au=Alfaro%2C+C+L&rft.aulast=Alfaro&rft.aufirst=C&rft.date=2001-01-01&rft.volume=35&rft.issue=4&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-13 N1 - Date created - 2002-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. AN - 71331125; 11208925 AB - Dietary restriction (DR; reduced calorie intake) increases the lifespan of rodents and increases their resistance to cancer, diabetes and other age-related diseases. DR also exerts beneficial effects on the brain including enhanced learning and memory and increased resistance of neurons to excitotoxic, oxidative and metabolic insults. The mechanisms underlying the effects of DR on neuronal plasticity and survival are unknown. In the present study we show that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex and striatum of mice maintained on an alternate day feeding DR regimen compared to animals fed ad libitum. Damage to hippocampal neurons induced by the excitotoxin kainic acid was significantly reduced in mice maintained on DR, and this neuroprotective effect was attenuated by intraventricular administration of a BDNF-blocking antibody. Our findings show that simply reducing food intake results in increased levels of BDNF in brain cells, and suggest that the resulting activation of BDNF signaling pathways plays a key role in the neuroprotective effect of DR. These results bolster accumulating evidence that DR may be an effective approach for increasing the resistance of the brain to damage and enhancing brain neuronal plasticity. JF - Journal of neurochemistry AU - Duan, W AU - Guo, Z AU - Mattson, M P AD - Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 619 EP - 626 VL - 76 IS - 2 SN - 0022-3042, 0022-3042 KW - Antibodies KW - 0 KW - Brain-Derived Neurotrophic Factor KW - Neurotoxins KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Kainic Acid -- administration & dosage KW - Animals KW - Cerebral Cortex -- cytology KW - Corpus Striatum -- cytology KW - Antibodies -- administration & dosage KW - Cell Count KW - Cerebral Cortex -- metabolism KW - Corpus Striatum -- metabolism KW - Cytoprotection KW - Neuronal Plasticity -- physiology KW - Energy Intake KW - Mice KW - Injections, Intraventricular KW - Body Weight KW - Signal Transduction -- physiology KW - Cell Survival -- drug effects KW - Neurotoxins -- administration & dosage KW - Mice, Inbred C57BL KW - Enzyme-Linked Immunosorbent Assay KW - Male KW - Brain-Derived Neurotrophic Factor -- metabolism KW - Neurons -- metabolism KW - Brain-Derived Neurotrophic Factor -- antagonists & inhibitors KW - Neurons -- drug effects KW - Neurons -- cytology KW - Hippocampus -- metabolism KW - Hippocampus -- cytology KW - Diet KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71331125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Brain-derived+neurotrophic+factor+mediates+an+excitoprotective+effect+of+dietary+restriction+in+mice.&rft.au=Duan%2C+W%3BGuo%2C+Z%3BMattson%2C+M+P&rft.aulast=Duan&rft.aufirst=W&rft.date=2001-01-01&rft.volume=76&rft.issue=2&rft.spage=619&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-15 N1 - Date created - 2002-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the dietary phytoestrogens daidzein and genistein on the incidence of vulvar carcinomas in 129/J mice. AN - 71330853; 12132873 AB - The objective of this study was to determine the effect of dietary phytoestrogens on the incidence of spontaneous vulvar carcinomas in 129/J mice using three natural ingredient diets and two purified diets containing predetermined levels of daidzein and genistein. Eighty weanling female mice without clinical evidence of vulvar carcinomas were randomly assigned 16 per diet to each of 5 test diets. Mice were clinically examined for vulvar masses weekly for 3 months and at monthly intervals thereafter. Vulvar carcinomas in representative groups of mice were confirmed using routine histological procedures. The incidence of vulvar carcinomas increased sharply in mice on all test diets during the first 2 months with minor changes during the remainder of the study. Within one month, the incidence of vulvar carcinomas in mice fed the AIN-76A modified soy protein diet was significantly (P < .05) increased over those of mice fed the AIN-76A modified casein diet, the #5K96, or the # 5058 diet. At three months, the incidence of vulvar carcinomas in mice fed the soy protein diet was significantly (P < .05) increased over those of mice fed the NIH-31 diet or the PMI #5K96 diet. There was a marginally significant (P < .10) correlation between the total daidzein and genistein levels in the five test diets and the incidence of vulvar carcinomas in mice as determined by clinical examination. We concluded that dietary levels of daidzein and genistein were associated with an increase in the incidence of vulvar carcinomas in mice and that the 129/J mouse may provide an animal model for studying the development of vulvar carcinomas. JF - Cancer detection and prevention AU - Thigpen, J E AU - Locklear, J AU - Haseman, J K AU - Saunders, H AU - Grant, M F AU - Forsythe, D B AD - Comparative Medicine Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 527 EP - 532 VL - 25 IS - 6 SN - 0361-090X, 0361-090X KW - Estrogens, Non-Steroidal KW - 0 KW - Isoflavones KW - Phytoestrogens KW - Plant Preparations KW - daidzein KW - 6287WC5J2L KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Animals KW - Incidence KW - Mice KW - Diet KW - Female KW - Vulvar Neoplasms -- pathology KW - Vulvar Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- pathology KW - Isoflavones -- toxicity KW - Estrogens, Non-Steroidal -- toxicity KW - Genistein -- toxicity KW - Carcinoma, Squamous Cell -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71330853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+detection+and+prevention&rft.atitle=Effects+of+the+dietary+phytoestrogens+daidzein+and+genistein+on+the+incidence+of+vulvar+carcinomas+in+129%2FJ+mice.&rft.au=Thigpen%2C+J+E%3BLocklear%2C+J%3BHaseman%2C+J+K%3BSaunders%2C+H%3BGrant%2C+M+F%3BForsythe%2C+D+B&rft.aulast=Thigpen&rft.aufirst=J&rft.date=2001-01-01&rft.volume=25&rft.issue=6&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Cancer+detection+and+prevention&rft.issn=0361090X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-06 N1 - Date created - 2002-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular targets for nutrients involved with cancer prevention. AN - 71312749; 12094610 AB - Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention. JF - Nutrition and cancer AU - Milner, J A AU - McDonald, S S AU - Anderson, D E AU - Greenwald, P AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA. jm524n@nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 1 EP - 16 VL - 41 IS - 1-2 SN - 0163-5581, 0163-5581 KW - Anticarcinogenic Agents KW - 0 KW - Stilbenes KW - Vitamin D KW - 1406-16-2 KW - Folic Acid KW - 935E97BOY8 KW - Genistein KW - DH2M523P0H KW - Selenium KW - H6241UJ22B KW - resveratrol KW - Q369O8926L KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Polymorphism, Genetic KW - Humans KW - Food Technology KW - Neoplasms -- prevention & control KW - Nutritional Physiological Phenomena KW - Diet KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71312749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Molecular+targets+for+nutrients+involved+with+cancer+prevention.&rft.au=Milner%2C+J+A%3BMcDonald%2C+S+S%3BAnderson%2C+D+E%3BGreenwald%2C+P&rft.aulast=Milner&rft.aufirst=J&rft.date=2001-01-01&rft.volume=41&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-13 N1 - Date created - 2002-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lactacystin enhances cisplatin sensitivity in resistant human ovarian cancer cell lines via inhibition of DNA repair and ERCC-1 expression. AN - 71302566; 11936875 AB - Cisplatin is among the most effective chemotherapeutic agents in the treatment of human ovarian cancer. The cytotoxicity of cisplatin results primarily from its ability to bind covalently to DNA and prevent DNA replication and transcription. The ubiquitin-proteasome pathway plays important roles in a broad array of basic cellular processes. Lactacystin is a selective inhibitor of the proteasome that can inhibit the ubiquitin pathway. However, the effect of lactacystin on DNA repair and the antitumor activity of cisplatin in ovarian cancer have not been evaluated. We report in this work that lactacystin, at concentrations that do not appear harmful, increased cisplatin toxicity in three resistant human ovarian carcinoma cell lines. In addition, lactacystin significantly enhanced DNA platination and decreased DNA repair of cisplatin-DNA adducts in these cell lines, as measured by atomic absorption spectrometry. Furthermore, Northem blot analysis and in vitro nuclear transcript elongation assay demonstrated that lactacystin dramatically reduced the steady-state mRNA expression and the rate of transcription of the DNA repair gene ERCC-1 in these cells. These observations indicate that proteasome inhibition has impact on nucleotide excision repair in several ways: i/ the normal ERCC-1 message upregulation is suppressed; ii/ cisplatin-DNA adduct repair is inhibited, and iii/ DNA platination, as well as cisplatin cytotoxicity, is enhanced. JF - Cellular and molecular biology (Noisy-le-Grand, France) AU - Li, Q Q AU - Yunmbam, M K AU - Zhong, X AU - Yu, J J AU - Mimnaugh, E G AU - Neckers, L AU - Reed, E AD - Medical Ovarian Cancer Section, Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. qli@hsc.wvu.edu Y1 - 2001 PY - 2001 DA - 2001 SP - OL61 EP - OL72 VL - 47 Online Pub SN - 0145-5680, 0145-5680 KW - Antineoplastic Agents KW - 0 KW - Cysteine Proteinase Inhibitors KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - Multienzyme Complexes KW - Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - lactacystin KW - 133343-34-7 KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Cisplatin KW - Q20Q21Q62J KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Gene Expression -- drug effects KW - DNA Damage KW - Humans KW - Cysteine Proteinase Inhibitors -- administration & dosage KW - Drug Resistance, Neoplasm KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - DNA, Neoplasm -- drug effects KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Multienzyme Complexes -- antagonists & inhibitors KW - DNA, Neoplasm -- genetics KW - Drug Synergism KW - DNA, Neoplasm -- metabolism KW - Female KW - RNA, Neoplasm -- metabolism KW - DNA Repair -- genetics KW - Ovarian Neoplasms -- metabolism KW - Antineoplastic Agents -- administration & dosage KW - Acetylcysteine -- analogs & derivatives KW - Ovarian Neoplasms -- genetics KW - Acetylcysteine -- administration & dosage KW - Proteins -- genetics KW - Ovarian Neoplasms -- drug therapy KW - DNA Repair -- drug effects KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71302566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+biology+%28Noisy-le-Grand%2C+France%29&rft.atitle=Lactacystin+enhances+cisplatin+sensitivity+in+resistant+human+ovarian+cancer+cell+lines+via+inhibition+of+DNA+repair+and+ERCC-1+expression.&rft.au=Li%2C+Q+Q%3BYunmbam%2C+M+K%3BZhong%2C+X%3BYu%2C+J+J%3BMimnaugh%2C+E+G%3BNeckers%2C+L%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=2001-01-01&rft.volume=47+Online+Pub&rft.issue=&rft.spage=OL61&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+biology+%28Noisy-le-Grand%2C+France%29&rft.issn=01455680&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-04 N1 - Date created - 2002-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophil-derived neurotoxin. AN - 71212220; 11582783 JF - Methods in enzymology AU - Rosenberg, H F AU - Domachowske, J B AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 273 EP - 286 VL - 341 SN - 0076-6879, 0076-6879 KW - Antiviral Agents KW - 0 KW - Recombinant Proteins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Eosinophils -- enzymology KW - Humans KW - Escherichia coli -- genetics KW - Cloning, Molecular -- methods KW - Ribonucleases -- isolation & purification KW - Ribonucleases -- genetics KW - Antiviral Agents -- isolation & purification KW - Antiviral Agents -- metabolism KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71212220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Eosinophil-derived+neurotoxin.&rft.au=Rosenberg%2C+H+F%3BDomachowske%2C+J+B&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=2001-01-01&rft.volume=341&rft.issue=&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2001-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Utilization of selenocysteine as a source of selenium for selenophosphate biosynthesis. AN - 71187784; 11568442 AB - Selenophosphate synthetase (SPS), the selD gene product from Escherichia coli, catalyzes the biosynthesis of monoselenophosphate from selenide and ATP. Characterization of selenophosphate synthetase revealed the determined K(m) value for selenide is far above the optimal concentration needed for growth and approached levels which are toxic. Selenocysteine lyase enzymes, which decompose selenocysteine to elemental selenium (Se(0)) and alanine, were considered as candidates for the control of free selenium levels in vivo. The ability of a lyase protein to generate Se(0) in the proximity of SPS maybe an attractive solution to selenium toxicity as well as the high K(m) value for selenide. Recently, three E. coli NifS-like proteins, CsdB, CSD, and IscS, were characterized. All three proteins exhibit lyase activity on L-cysteine and L-selenocysteine and produce sulfane sulfur, S(0), or Se(0) respectively. Each lyase can effectively mobilize Se(0) from L-selenocysteine for selenophosphate biosynthesis. JF - BioFactors (Oxford, England) AU - Lacourciere, G M AU - Stadtman, T C AD - Laboratory of Biochemistry, National Institutes of Health, NHLBI, 50 South Drive, Room 2126, Bethesda, MD 20892, USA. lacourcg@nhlbi.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 69 EP - 74 VL - 14 IS - 1-4 SN - 0951-6433, 0951-6433 KW - Drosophila Proteins KW - 0 KW - Phosphates KW - Proteins KW - Selenium Compounds KW - Selenoproteins KW - Selenocysteine KW - 0CH9049VIS KW - selenophosphate KW - 12509-41-0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Phosphotransferases KW - EC 2.7.- KW - selenophosphate synthetase KW - EC 2.7.9.3 KW - Lyases KW - EC 4.- KW - Carbon-Sulfur Lyases KW - EC 4.4.- KW - cysteine desulfurase KW - EC 4.4.1.- KW - selenocysteine lyase KW - EC 4.4.1.16 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Protein Biosynthesis KW - Carbon-Sulfur Lyases -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Lyases -- metabolism KW - Phosphotransferases -- genetics KW - Phosphates -- metabolism KW - Selenium -- metabolism KW - Escherichia coli -- metabolism KW - Selenocysteine -- metabolism KW - Selenium -- pharmacology KW - Escherichia coli -- genetics KW - Phosphotransferases -- metabolism KW - Selenium Compounds -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71187784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioFactors+%28Oxford%2C+England%29&rft.atitle=Utilization+of+selenocysteine+as+a+source+of+selenium+for+selenophosphate+biosynthesis.&rft.au=Lacourciere%2C+G+M%3BStadtman%2C+T+C&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=2001-01-01&rft.volume=14&rft.issue=1-4&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=BioFactors+%28Oxford%2C+England%29&rft.issn=09516433&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sustained elevation of calcium induces Ca(2+)/calmodulin-dependent protein kinase II clusters in hippocampal neurons. AN - 71186083; 11564417 AB - Treatment of cultured hippocampal neurons with the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) in the absence of glucose mimics ischemic energy depletion and induces formation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) clusters, spherical structures with diameters of 75-175 nm [Dosemeci et al., J. Neurosci. 20 (2000) 3076-3084]. The demonstration that CaMKII clustering occurs in the intact, adult rat brain upon interruption of blood flow indicates that clustering is not confined to cell cultures. Application of N-methyl-D-aspartate (250 microM, 15 min) to hippocampal cultures also induces cluster formation, suggesting a role for Ca(2+). Indeed, intracellular Ca(2+) monitored with Fluo3-AM by confocal microscopy reaches a sustained high level within 5 min of CCCP treatment. The appearance of immunolabeled CaMKII clusters, detected by electron microscopy, follows the onset of the sustained increase in intracellular Ca(2+). Moreover, CaMKII does not cluster when the rise in intracellular Ca(2+) is prevented by the omission of extracellular Ca(2+) during CCCP treatment, confirming that clustering is Ca(2+)-dependent. A lag period of 1-2 min between the onset of high intracellular Ca(2+) levels and the formation of CaMKII clusters suggests that a sustained increase in Ca(2+) level is necessary for the clustering. CaMKII clusters disappear within 2 h of returning the cultures to normal incubation conditions, at which time no significant cell death is detected. These results indicate that pathological conditions that promote sustained episodes of Ca(2+) overload result in a transitory clustering of CaMKII into spherical structures. CaMKII clustering may represent a cellular defense mechanism to sequester a portion of the CaMKII pool, thereby preventing excessive protein phosphorylation. JF - Neuroscience AU - Tao-Cheng, J H AU - Vinade, L AU - Smith, C AU - Winters, C A AU - Ward, R AU - Brightman, M W AU - Reese, T S AU - Dosemeci, A AD - Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 69 EP - 78 VL - 106 IS - 1 SN - 0306-4522, 0306-4522 KW - Chelating Agents KW - 0 KW - Excitatory Amino Acid Agonists KW - Neurotoxins KW - Uncoupling Agents KW - Carbonyl Cyanide m-Chlorophenyl Hydrazone KW - 555-60-2 KW - N-Methylaspartate KW - 6384-92-5 KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Fetus KW - Age Factors KW - Cytoplasm -- ultrastructure KW - Protein Structure, Tertiary -- drug effects KW - Neurotoxins -- pharmacology KW - Cytoplasm -- pathology KW - Rats KW - Chelating Agents -- pharmacology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Protein Structure, Tertiary -- physiology KW - Microscopy, Electron KW - Extracellular Space -- enzymology KW - Time Factors KW - Extracellular Space -- drug effects KW - Carbonyl Cyanide m-Chlorophenyl Hydrazone -- pharmacology KW - Cell Culture Techniques KW - Cells, Cultured -- ultrastructure KW - Cells, Cultured -- pathology KW - Uncoupling Agents -- pharmacology KW - Rats, Sprague-Dawley KW - N-Methylaspartate -- pharmacology KW - Cells, Cultured -- enzymology KW - Cytoplasm -- enzymology KW - Immunohistochemistry KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Energy Metabolism -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- drug effects KW - Neurons -- ultrastructure KW - Neurons -- pathology KW - Calcium -- metabolism KW - Energy Metabolism -- drug effects KW - Hippocampus -- physiopathology KW - Neurons -- enzymology KW - Hippocampus -- enzymology KW - Hippocampus -- pathology KW - Intracellular Fluid -- drug effects KW - Intracellular Fluid -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71186083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Sustained+elevation+of+calcium+induces+Ca%282%2B%29%2Fcalmodulin-dependent+protein+kinase+II+clusters+in+hippocampal+neurons.&rft.au=Tao-Cheng%2C+J+H%3BVinade%2C+L%3BSmith%2C+C%3BWinters%2C+C+A%3BWard%2C+R%3BBrightman%2C+M+W%3BReese%2C+T+S%3BDosemeci%2C+A&rft.aulast=Tao-Cheng&rft.aufirst=J&rft.date=2001-01-01&rft.volume=106&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide and vasospasm. AN - 71183720; 11563311 JF - Acta neurochirurgica. Supplement AU - Pluta, R M AU - Thompson, B G AU - Afshar, J K AU - Boock, R J AU - Iuliano, B AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 67 EP - 72 VL - 77 SN - 0065-1419, 0065-1419 KW - Hydrazines KW - 0 KW - Nitric Oxide Donors KW - Nitrogen Oxides KW - Oxidants KW - proline-nitric oxide KW - Nitric Oxide KW - 31C4KY9ESH KW - 1,1-diethyl-2-hydroxy-2-nitrosohydrazine KW - 86831-65-4 KW - Arginine KW - 94ZLA3W45F KW - Proline KW - 9DLQ4CIU6V KW - Hydrogen Peroxide KW - BBX060AN9V KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Arginine -- therapeutic use KW - Animals KW - Humans KW - Astrocytes -- physiology KW - Oxidants -- poisoning KW - Haplorhini KW - Rats KW - Hydrogen Peroxide -- poisoning KW - Nitric Oxide Donors -- pharmacology KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Hydrazines -- pharmacology KW - Nitric Oxide Donors -- therapeutic use KW - Nitric Oxide Synthase -- metabolism KW - Vasospasm, Intracranial -- physiopathology KW - Nitric Oxide -- physiology KW - Vasospasm, Intracranial -- drug therapy KW - Proline -- therapeutic use KW - Nitric Oxide -- therapeutic use KW - Proline -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71183720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+neurochirurgica.+Supplement&rft.atitle=Nitric+oxide+and+vasospasm.&rft.au=Pluta%2C+R+M%3BThompson%2C+B+G%3BAfshar%2C+J+K%3BBoock%2C+R+J%3BIuliano%2C+B%3BOldfield%2C+E+H&rft.aulast=Pluta&rft.aufirst=R&rft.date=2001-01-01&rft.volume=77&rft.issue=&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Acta+neurochirurgica.+Supplement&rft.issn=00651419&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-06 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Animal models used in the screening of antiepileptic drugs. AN - 71180141; 11564118 AB - The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. These models can be either in vivo or in vitro, mechanism specific, mechanism independent, or seizure specific. To be predictive of therapeutic activity in patients, the models should approximate the events that precipitate seizures in humans. Model validation is defined by determining the pharmacologic characteristics using known clinically effective drugs. Mechanism-independent models were used to identify the first antiepileptic drugs [AEDs; e.g., phenobarbital (PB) and phenytoin (PHT)]. Mechanism-specific models are based on the fundamental process by which seizure propagation and inhibition occurs. Seizure-type models identify a compound's potential based on its effects on electrographic and behavioral response. No single model can be used to identify potential compounds adequately for development. The full pharmacologic-anticonvulsant profile of a potentially useful new therapeutic agent is required to ensure successful development. JF - Epilepsia AU - Kupferberg, H AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-9523, USA. hkupfer@worldnet.att.net Y1 - 2001 PY - 2001 DA - 2001 SP - 7 EP - 12 VL - 42 Suppl 4 SN - 0013-9580, 0013-9580 KW - Anticonvulsants KW - 0 KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Papio KW - Animals KW - Gerbillinae KW - Electrodes, Implanted KW - Mice KW - Electric Stimulation KW - Rats, Inbred Strains KW - Rats KW - Mice, Inbred Strains KW - Amygdala -- physiology KW - Acoustic Stimulation KW - Kindling, Neurologic -- physiology KW - Drug Evaluation, Preclinical KW - Anticonvulsants -- pharmacology KW - Epilepsy -- physiopathology KW - Anticonvulsants -- toxicity KW - Disease Models, Animal KW - Epilepsy -- drug therapy KW - Anticonvulsants -- therapeutic use KW - Epilepsy -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71180141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Animal+models+used+in+the+screening+of+antiepileptic+drugs.&rft.au=Kupferberg%2C+H&rft.aulast=Kupferberg&rft.aufirst=H&rft.date=2001-01-01&rft.volume=42+Suppl+4&rft.issue=&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opioids in non-cancer pain: a life-time sentence? AN - 71179004; 11558990 AB - There is continuing reluctance to prescribe strong opioids for the management of chronic non-cancer pain due to concerns about side-effects, physical tolerance, withdrawal and addiction. Randomized controlled trials have now provided evidence for the efficacy of opioids against both nociceptive and neuropathic pain. However, there is considerable variability in response rates, possibly depending on the type of pain, the type of opioid and its route of administration, the time to follow-up, compliance and the development of tolerance. Five patients were selected with nociceptive or neuropathic pain in whom other pharmacological or physical therapies had failed to provide satisfactory pain relief. They received transdermal fentanyl (starting dose 25 microg/h) for at least 6 weeks. Transdermal fentanyl dosage was titrated upwards as required. Transdermal fentanyl provided adequate pain relief in patients with nociceptive pain (diabetic ulcer, osteoporotic vertebral fracture, ankylosing spondylitis) or neuropathic pain with a nociceptive component (radicular pain due to disc protrusion, herpetic neuralgia). The duration of treatment ranged from 6 weeks to 6 months for four cases. In the case of ankylosing spondylitis, treatment was carried out for 2 years, stopped and then restarted successfully. There were no withdrawal effects or addictive behaviour on treatment cessation, regardless of duration of the treatment. In conclusion, strong opioids may provide prolonged effective pain relief in selected patients with nociceptive and neuropathic non-cancer pain. Transdermal fentanyl treatment can often be temporary and can easily be stopped following adequate pain relief without withdrawal effects or any evidence of addictive behaviour. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain. JF - European journal of pain (London, England) AU - Dellemijn, P L AD - Department of Neurology and Neurophysiology, Saint Joseph Hospital, P.O. Box 7777, 5500 MB Veldhoven, Netherlands. NEI@sjz.nl Y1 - 2001 PY - 2001 DA - 2001 SP - 333 EP - 339 VL - 5 IS - 3 SN - 1090-3801, 1090-3801 KW - Analgesics, Opioid KW - 0 KW - Fentanyl KW - UF599785JZ KW - Index Medicus KW - Low Back Pain -- drug therapy KW - Administration, Cutaneous KW - Drug Administration Schedule KW - Herpes Zoster -- drug therapy KW - Diabetic Neuropathies -- physiopathology KW - Humans KW - Aged KW - Quality of Life -- psychology KW - Herpes Zoster -- physiopathology KW - Diabetic Neuropathies -- drug therapy KW - Adult KW - Treatment Outcome KW - Low Back Pain -- physiopathology KW - Middle Aged KW - Chronic Disease KW - Spondylitis, Ankylosing -- drug therapy KW - Spondylitis, Ankylosing -- physiopathology KW - Male KW - Female KW - Pain, Intractable -- drug therapy KW - Fentanyl -- adverse effects KW - Analgesics, Opioid -- adverse effects KW - Analgesics, Opioid -- administration & dosage KW - Fentanyl -- administration & dosage KW - Pain, Intractable -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71179004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pain+%28London%2C+England%29&rft.atitle=Opioids+in+non-cancer+pain%3A+a+life-time+sentence%3F&rft.au=Dellemijn%2C+P+L&rft.aulast=Dellemijn&rft.aufirst=P&rft.date=2001-01-01&rft.volume=5&rft.issue=3&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pain+%28London%2C+England%29&rft.issn=10903801&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Base excision repair in nuclear and mitochondrial DNA. AN - 71163322; 11554304 AB - Base excision repair mechanisms have been analyzed in nuclear and mitochondrial DNA. We measured the size and position of the newly incorporated DNA repair patch in various DNA substrates containing single oxidative lesions. Repair of 8-oxoguanine and of thymine glycol is almost exclusively via the base excision repair (BER) pathway with little or no involvement of nucleotide excision repair (NER). The repair mode is generally via the single-nucleotide replacement pathway with little incorporation into longer patches. Extension of these studies suggests that DNA polymerase beta plays a critical role not only in the short-patch repair process but also in the long-patch, PCNA-dependent pathway. Mitochondria are targets for a heavy load of oxidative DNA damage. They have efficient BER repair capacity, but cannot repair most bulky lesions normally repaired by NER. In vitro experiments performed using rat and human mitochondrial extracts suggest that the repair incorporation during the removal of uracil in DNA occurs via the short-patch repair BER pathway. Oxidative DNA damage accumulates with age in mitochondrial DNA, but this cannot be explained by an attenuation of DNA repair. In contrast, we observe that mitochondrial incision of 8-oxoG increases with age in rodents. JF - Progress in nucleic acid research and molecular biology AU - Dianov, G L AU - Souza-Pinto, N AU - Nyaga, S G AU - Thybo, T AU - Stevnsner, T AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, NIH Baltimore, Maryland 21224, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 285 EP - 297 VL - 68 SN - 0079-6603, 0079-6603 KW - DNA, Mitochondrial KW - 0 KW - Oxidants KW - Proliferating Cell Nuclear Antigen KW - 1,N(6)-ethenoadenine KW - 13875-63-3 KW - thymine glycol KW - 2943-56-8 KW - Hypoxanthine KW - 2TN51YD919 KW - 3-methyladenine KW - 5142-23-4 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - 3-methyladenine-DNA glycosylase KW - EC 3.2.2.- KW - DNA Glycosylases KW - N-Glycosyl Hydrolases KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - Adenine KW - JAC85A2161 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Aging -- metabolism KW - Animals KW - DNA Damage KW - Mitochondria -- enzymology KW - Hypoxanthine -- metabolism KW - Lymphocytes -- metabolism KW - Mice KW - Mammals -- genetics KW - Rats KW - Oxidation-Reduction KW - Base Sequence KW - Proliferating Cell Nuclear Antigen -- physiology KW - DNA Polymerase beta -- physiology KW - Oxidative Stress KW - Point Mutation KW - Oxidants -- toxicity KW - Molecular Sequence Data KW - Mammals -- metabolism KW - Lymphocytes -- ultrastructure KW - Aging -- genetics KW - Cell Line KW - N-Glycosyl Hydrolases -- physiology KW - Cell-Free System KW - Thymine -- analogs & derivatives KW - DNA Repair KW - Adenine -- metabolism KW - Thymine -- metabolism KW - Cell Nucleus -- metabolism KW - DNA -- metabolism KW - DNA, Mitochondrial -- metabolism KW - DNA -- genetics KW - Guanine -- analogs & derivatives KW - Adenine -- analogs & derivatives KW - Guanine -- metabolism KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71163322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+nucleic+acid+research+and+molecular+biology&rft.atitle=Base+excision+repair+in+nuclear+and+mitochondrial+DNA.&rft.au=Dianov%2C+G+L%3BSouza-Pinto%2C+N%3BNyaga%2C+S+G%3BThybo%2C+T%3BStevnsner%2C+T%3BBohr%2C+V+A&rft.aulast=Dianov&rft.aufirst=G&rft.date=2001-01-01&rft.volume=68&rft.issue=&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Progress+in+nucleic+acid+research+and+molecular+biology&rft.issn=00796603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelial monocyte activating polypeptide II (EMAP II) enhances the effect of TNF on tumor-associated vasculature. AN - 71131075; 11527006 AB - Endothelial monocyte activating polypeptide II (EMAP II) was initially identified as a factor that may modulate the interaction of tumor necrosis factor (TNF) with tumor vascular endothelium. Since the toxicity of TNF has continued to hamper its clinical use in cancer patients, investigators have developed a renewed interest in modulators such as EMAP II. Over a period of 25 years, investigations into the mechanism of antitumor action of TNF have yielded important observations concerning the role of the microvasculature as the target for TNF's activity. EMAP II was identified as an endothelial response mediator secreted by a highly TNF-sensitive tumor line, the Meth A fibrosarcoma. When used to treat tumors, either by systemic administration of recombinant protein or by gene transfer, EMAP II upregulates cellular receptors for TNF on endothelial cells and confers TNF sensitivity to tumors previously believed to be TNF-resistant. Potential mechanisms for EMAP II's selective effects on endothelial cells have been described. These include induction of endothelial cell apoptosis and upregulation of TNF receptor I (TNFR1). Other recent investigations have posited various physiological roles for EMAP II, ranging from the mediation of inflammation to the vascular remodeling that occurs during normal embryogenesis. EMAP II has generated interest as a modulator of TNF response for isolated whole-organ, isolated limb, or systemic perfusion. By enhancing the tumor vasculature response to TNF, EMAP II may enable lower, non-toxic doses of TNF to be used to clinical advantage. JF - Current opinion in investigational drugs (London, England : 2000) AU - Kayton, M L AU - Libutti, S K AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. KaytonM@pop.nci.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 136 EP - 138 VL - 2 IS - 1 SN - 1472-4472, 1472-4472 KW - Cytokines KW - 0 KW - Neoplasm Proteins KW - RNA-Binding Proteins KW - Receptors, Tumor Necrosis Factor KW - Tumor Necrosis Factor-alpha KW - small inducible cytokine subfamily E, member 1 KW - Index Medicus KW - Animals KW - Humans KW - Apoptosis -- drug effects KW - Receptors, Tumor Necrosis Factor -- analysis KW - Receptors, Tumor Necrosis Factor -- drug effects KW - Drug Synergism KW - RNA-Binding Proteins -- analysis KW - Neoplasms -- blood supply KW - RNA-Binding Proteins -- therapeutic use KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Neoplasm Proteins -- therapeutic use KW - RNA-Binding Proteins -- pharmacology KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Neoplasm Proteins -- analysis KW - Neoplasm Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71131075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.atitle=Endothelial+monocyte+activating+polypeptide+II+%28EMAP+II%29+enhances+the+effect+of+TNF+on+tumor-associated+vasculature.&rft.au=Kayton%2C+M+L%3BLibutti%2C+S+K&rft.aulast=Kayton&rft.aufirst=M&rft.date=2001-01-01&rft.volume=2&rft.issue=1&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.issn=14724472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Survival effects of pigment epithelium-derived factor expressed by a lentiviral vector in rat cerebellar granule cells. AN - 71105893; 11509837 AB - We have previously shown that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cells (CGCs), by blocking apoptotic death, and can also protect these cells against glutamate-induced neurotoxicity. In preparation for gene therapy studies, pseudotyped HIV-1-based lentiviral vectors containing the PEDF gene, as well as either green fluorescent protein or beta-galactosidase, were prepared. These bicistronic vectors are unique in that they express two genes efficiently under one promoter. Primary cell cultures of CGCs from postnatal day 8 rats were infected with the vectors encoding PEDF. RT-PCR demonstrated expression of mRNA and Western blot analysis confirmed that infected CGCs secrete PEDF protein to the medium. Assays for cell survival demonstrated that PEDF-infected cells were significantly more protected compared with mock-infected controls for 6-8 days in culture, as well as against induced apoptosis. The PEDF vectors expressing tat (trans-acting transcription factor) provided more protection than the tat(-) vectors. These results demonstrate that while the lentiviral vectors expressing PEDF are as neuroprotective as the protein itself for CGCs, the vectors have the advantage of providing long-lasting expression of PEDF protein, which will be more effective in in vivo studies. The present results suggest that this system may be useful for gene therapy for neurodegenerative disorders. Copyright 2001 S. Karger AG, Basel JF - Developmental neuroscience AU - Nomura, T AU - Yabe, T AU - Mochizuki, H AU - Reiser, J AU - Becerra, S P AU - Schwartz, J P AD - Neurotrophic Factors Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. 20892-4126, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 145 EP - 152 VL - 23 IS - 2 SN - 0378-5866, 0378-5866 KW - Eye Proteins KW - 0 KW - Gene Products, tat KW - Nerve Growth Factors KW - Proteins KW - RNA, Messenger KW - Serpins KW - pigment epithelium-derived factor KW - Index Medicus KW - Animals KW - Apoptosis KW - Gene Expression Regulation, Viral KW - RNA, Messenger -- analysis KW - Cell Survival KW - Rats KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Cells, Cultured KW - Gene Products, tat -- genetics KW - Immunohistochemistry KW - Lac Operon KW - Gene Expression Regulation, Developmental KW - Serpins -- secretion KW - Proteins -- secretion KW - Cerebellum -- cytology KW - Lentivirus KW - Genetic Vectors KW - Serpins -- analysis KW - Proteins -- analysis KW - Serpins -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71105893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+neuroscience&rft.atitle=Survival+effects+of+pigment+epithelium-derived+factor+expressed+by+a+lentiviral+vector+in+rat+cerebellar+granule+cells.&rft.au=Nomura%2C+T%3BYabe%2C+T%3BMochizuki%2C+H%3BReiser%2C+J%3BBecerra%2C+S+P%3BSchwartz%2C+J+P&rft.aulast=Nomura&rft.aufirst=T&rft.date=2001-01-01&rft.volume=23&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Developmental+neuroscience&rft.issn=03785866&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Self-reported alcohol use and abuse by arrestees in the 1998 Arrestee Drug Abuse Monitoring Program. AN - 71103813; 11496970 AB - Data collected in the Arrestee Drug Abuse Monitoring (ADAM) program on alcohol and other drug use among arrestees provide a valuable opportunity to examine the relationship between alcohol use and violence. The data are used to explore the combined use of alcohol and other drugs among offenders and the relationships between substance use and the offenders' demographic characteristics and offenses. These findings are used to identify changes in the offenders' alcohol and other drug use over time. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Martin, S E AU - Bryant, K AU - Fitzgerald, N AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 72 EP - 79 VL - 25 IS - 1 SN - 1535-7414, 1535-7414 KW - Street Drugs KW - 0 KW - Index Medicus KW - Aged, 80 and over KW - Substance Abuse Detection KW - Humans KW - Adult KW - Aged KW - Substance-Related Disorders -- complications KW - Middle Aged KW - Self-Assessment KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- epidemiology KW - Alcohol Drinking -- psychology KW - Crime -- statistics & numerical data KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71103813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Self-reported+alcohol+use+and+abuse+by+arrestees+in+the+1998+Arrestee+Drug+Abuse+Monitoring+Program.&rft.au=Martin%2C+S+E%3BBryant%2C+K%3BFitzgerald%2C+N&rft.aulast=Martin&rft.aufirst=S&rft.date=2001-01-01&rft.volume=25&rft.issue=1&rft.spage=72&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Individual differences in alcohol-induced aggression. A nonhuman-primate model. AN - 71071613; 11496962 AB - Some people are more likely than others to become aggressive after consuming alcohol. Researchers studying alcohol use and aggression hope to identify individual differences in behavior and biochemistry that exist among subjects who become aggressive following alcohol consumption. Research with nonhuman primates has shown that individual differences in brain chemistry predict impulsivity, aggression, and alcohol-induced aggression. These differences appear to be associated with early rearing experiences and remain stable throughout the individual's life. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Higley, J D AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 12 EP - 19 VL - 25 IS - 1 SN - 1535-7414, 1535-7414 KW - Serotonin KW - 333DO1RDJY KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Central Nervous System -- growth & development KW - Serotonin -- physiology KW - Brain Chemistry KW - Violence KW - Primates KW - Models, Animal KW - Ethanol -- adverse effects KW - Behavior, Animal -- drug effects KW - Aggression -- drug effects KW - Behavior, Animal -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71071613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Individual+differences+in+alcohol-induced+aggression.+A+nonhuman-primate+model.&rft.au=Higley%2C+J+D&rft.aulast=Higley&rft.aufirst=J&rft.date=2001-01-01&rft.volume=25&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerability of postexposure antiretroviral prophylaxis for occupational exposures to HIV. AN - 71044999; 11480491 AB - A substantial body of evidence provides support (but not definitive proof of efficacy) for the use of antiretroviral agents as postexposure prophylaxis for occupational exposures to HIV in the healthcare workplace. Despite the lack of definitive evidence of the efficacy of these agents in this setting, over the past decade this intervention has become the standard of care for healthcare workers who sustain occupational exposures to HIV. Administration of these agents--even for a relatively short 28-day postexposure course--is often fraught with difficulty. All of the agents currently used for postexposure prophylaxis regimens have substantial adverse effects, and significant adverse effects occur in more than two-thirds of individuals electing prophylaxis. This manuscript reiterates current US Federal Government guidelines for the administration of postexposure prophylaxis, specifically noting that zidovudine plus lamivudine (with or without a protease inhibitor) remains the recommended regimen. The paper summarises the significant toxicities associated with nucleoside reverse transcriptase inhibitors (primarily nausea, vomiting, diarrhoea and bone marrow suppression), non-nucleoside reverse transcriptase inhibitors (rash, fever, gastrointestinal symptoms and hepatitis, including hepatic decompensation necessitating liver transplantation) and protease inhibitors (nausea, vomiting, diarrhoea, abdominal pain, hyperglycaemia, hyperlipidaemia, headache and anorexia). As a class, the antiretroviral agents have an extraordinary number of drug interactions. The non-nucleoside reverse transcriptase inhibitors and the protease inhibitors are metabolised through the cytochrome P450 pathway, and the effects of concomitant administration of protease inhibitors with other agents in the same class are discussed, as well as the effects of concomitant administration of protease inhibitors with non-nucleoside agents. The potential for numerous and medically risky drug interactions emphasises the importance of planning antiretroviral prophylaxis in consultation with practitioners or clinical pharmacists who are skilled in the use of these agents and knowledgeable about the potential for significant drug interactions that could either reduce the benefit of prophylaxis or increase the potential for toxicity. Another common problem encountered by individuals managing postexposure prophylaxis programmes relates to the administration of chemoprophylaxis to a pregnant healthcare worker who has sustained an occupational exposure to HIV. We address what is known about the potential for toxicity and emphasise the recently published warning concerning the deaths of pregnant women and their offspring from lactic acidosis while receiving regimens containing stavudine and didanosine. JF - Drug safety AU - Lee, L M AU - Henderson, D K AD - Office of the Deputy Director for Clinical Care, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 587 EP - 597 VL - 24 IS - 8 SN - 0114-5916, 0114-5916 KW - Anti-HIV Agents KW - 0 KW - HIV Protease Inhibitors KW - Reverse Transcriptase Inhibitors KW - Index Medicus KW - United States KW - Drug Interactions KW - Reverse Transcriptase Inhibitors -- administration & dosage KW - Humans KW - Infectious Disease Transmission, Patient-to-Professional KW - HIV Protease Inhibitors -- therapeutic use KW - Pregnancy KW - Reverse Transcriptase Inhibitors -- adverse effects KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - Patient Compliance KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - HIV Protease Inhibitors -- administration & dosage KW - Female KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- prevention & control KW - Health Personnel KW - Anti-HIV Agents -- adverse effects KW - Anti-HIV Agents -- administration & dosage KW - Occupational Exposure -- adverse effects KW - HIV Infections -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71044999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+safety&rft.atitle=Tolerability+of+postexposure+antiretroviral+prophylaxis+for+occupational+exposures+to+HIV.&rft.au=Lee%2C+L+M%3BHenderson%2C+D+K&rft.aulast=Lee&rft.aufirst=L&rft.date=2001-01-01&rft.volume=24&rft.issue=8&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Drug+safety&rft.issn=01145916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA amplification associated with double minutes originating from chromosome 19 in mouse hepatocellular carcinoma. AN - 71040042; 11474192 AB - DNA amplification is associated with genomic instability, the main characteristic of cancer cells, and it frequently involves protooncogenes. Double minute chromosomes (DM) and homogeneously stained regions (HSR) are cytological manifestations of DNA amplification. Gain of chromosome 19 is a recurrent alteration in mouse hepatocellular carcinoma (HCC). In one tumor cell line established from HCC developed in myc transgenic mice, DM derived from chromosome 19 were identified by spectral karyotyping and confirmed by fluorescence in situ hybridization (FISH). A probe generated by PCR from microdissected DM was localized by FISH on normal and HCC-derived cell lines on DM and chromosome 19 at two sites separated by several medium size G-bands. This organization of DM containing amplified sequences from separate loci of the same chromosome, indicates a complex mechanism of DNA amplification, possibly involving more than one gene. DM or HSR were not previously identified in mouse HCC and adult human HCC. The recognition of these loci could lead to the cloning of new genes or identification of known genes important in development or progression of HCC. Copyright 2001 S. Karger AG, Basel JF - Cytogenetics and cell genetics AU - Zimonjic, D B AU - Zhang, H AU - Shan, Z AU - Factor, V AU - Trent, J AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute/NIH, 37 Convent Drive MSC 4255, Bethesda, Maryland 20892-4255, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 114 EP - 116 VL - 93 IS - 1-2 SN - 0301-0171, 0301-0171 KW - DNA Probes KW - 0 KW - Index Medicus KW - Karyotyping KW - Animals KW - Tumor Cells, Cultured KW - Chromosome Banding KW - In Situ Hybridization, Fluorescence KW - Disease Progression KW - Mice KW - Mice, Transgenic KW - Genes, myc -- genetics KW - Liver Neoplasms, Experimental -- genetics KW - Gene Amplification -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Mutation -- genetics KW - Chromosomes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71040042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=DNA+amplification+associated+with+double+minutes+originating+from+chromosome+19+in+mouse+hepatocellular+carcinoma.&rft.au=Zimonjic%2C+D+B%3BZhang%2C+H%3BShan%2C+Z%3BFactor%2C+V%3BTrent%2C+J%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=2001-01-01&rft.volume=93&rft.issue=1-2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGF-beta signaling in mammary gland development and tumorigenesis. AN - 71031776; 11467453 AB - Ligands of the TGF-beta superfamily are unique in that they signal through transmembrane receptor serine-threonine kinases, rather than tyrosine kinases. The receptor complex couples to a signal transduction pathway involving a novel family of proteins, the Smads. On phosphorylation, Smads translocate to the nucleus where they modulate transcriptional responses. However, TGF-betas can also activate the mitogen-activated protein kinase (MAPK)4 pathway, and the different biological responses to TGF-beta depend to varying degrees on activation of either or both of these two pathways. The Smad pathway is a nexus for cross-talk with other signal transduction pathways and for modulation by many different interacting proteins. Despite compelling evidence that TGF-beta has tumor suppressor activity in the mammary gland, neither TGF-beta receptors nor Smads are genetically inactivated in human breast cancer, though receptor expression is reduced. Possible reasons are discussed in relation to the dual role of TGF-beta as tumor suppressor and oncogene. JF - Journal of mammary gland biology and neoplasia AU - Wakefield, L M AU - Piek, E AU - Böttinger, E P AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. wakefiel@dce41.nci.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 67 EP - 82 VL - 6 IS - 1 SN - 1083-3021, 1083-3021 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Female KW - Signal Transduction -- physiology KW - Mammary Neoplasms, Animal -- metabolism KW - Breast -- growth & development KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71031776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+mammary+gland+biology+and+neoplasia&rft.atitle=TGF-beta+signaling+in+mammary+gland+development+and+tumorigenesis.&rft.au=Wakefield%2C+L+M%3BPiek%2C+E%3BB%C3%B6ttinger%2C+E+P&rft.aulast=Wakefield&rft.aufirst=L&rft.date=2001-01-01&rft.volume=6&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Journal+of+mammary+gland+biology+and+neoplasia&rft.issn=10833021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-20 N1 - Date created - 2001-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Understanding the interaction between environmental exposures and molecular events in colorectal carcinogenesis. AN - 71027625; 11458819 JF - Cancer investigation AU - Ishibe, N AU - Freedman, A N AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., EPS 7236, Rockville, MD 20892, USA. Ishiben@exchange.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 524 EP - 539 VL - 19 IS - 5 SN - 0735-7907, 0735-7907 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cell Cycle Proteins KW - Enzyme Inhibitors KW - Microtubule-Associated Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Folic Acid KW - 935E97BOY8 KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - Methylenetetrahydrofolate Reductase (NADPH2) KW - EC 1.5.1.20 KW - Index Medicus KW - Genes, DCC -- genetics KW - Humans KW - Smoking -- adverse effects KW - Genes, bcl-2 -- drug effects KW - Microtubule-Associated Proteins -- genetics KW - Genes, APC -- drug effects KW - Genes, ras -- genetics KW - Folic Acid -- metabolism KW - Dietary Fiber -- administration & dosage KW - Oxidoreductases Acting on CH-NH Group Donors -- genetics KW - Genes, p53 -- genetics KW - Adenoma -- chemically induced KW - Apoptosis -- drug effects KW - Cell Transformation, Neoplastic -- chemically induced KW - Enzyme Inhibitors -- pharmacology KW - Adenoma -- genetics KW - Methylation KW - Cell Transformation, Neoplastic -- genetics KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Carcinoma -- chemically induced KW - Carcinoma -- genetics KW - Mutation -- drug effects KW - Genes, Tumor Suppressor -- drug effects KW - Colorectal Neoplasms -- genetics KW - Environmental Exposure -- adverse effects KW - Colorectal Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71027625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=Understanding+the+interaction+between+environmental+exposures+and+molecular+events+in+colorectal+carcinogenesis.&rft.au=Ishibe%2C+N%3BFreedman%2C+A+N&rft.aulast=Ishibe&rft.aufirst=N&rft.date=2001-01-01&rft.volume=19&rft.issue=5&rft.spage=524&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The links between alcohol, crime and the criminal justice system: explanations, evidence and interventions. AN - 71023182; 11444156 AB - Many studies indicate that alcohol abuse and dependence are closely linked with the criminal justice system (CJS). Alcohol was consumed prior to about half of all homicides and assaults, and nearly 40 percent of state prisoners report committing their current offense under the influence of alcohol. Alcohol abuse cost approximately $13 billion in 1992 non-health related costs. This article seeks to address this burden on the CJS and society. It presents a conceptual framework for explaining the alcohol-crime nexus, reviews empirical evidence of the complex associations between alcohol consumption and crime, and links these with promising intervention strategies to reduce alcohol-related crime. JF - The American journal on addictions AU - Martin, S E AD - National Institute on Alcohol Abuse and Alcoholism, 6000 Executive Blvd., Rockville, MD 20982, USA. smartin@willco.niaaa.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 136 EP - 158 VL - 10 IS - 2 SN - 1055-0496, 1055-0496 KW - Index Medicus KW - Cognitive Therapy KW - Humans KW - Adult KW - Community-Institutional Relations KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Crime -- statistics & numerical data KW - Criminal Law KW - Alcoholism -- prevention & control KW - Crime -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71023182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+on+addictions&rft.atitle=The+links+between+alcohol%2C+crime+and+the+criminal+justice+system%3A+explanations%2C+evidence+and+interventions.&rft.au=Martin%2C+S+E&rft.aulast=Martin&rft.aufirst=S&rft.date=2001-01-01&rft.volume=10&rft.issue=2&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-02 N1 - Date created - 2001-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The outcome of treatment. Overview. AN - 70992520; 11449750 JF - Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism AU - Huebner, R B AU - Fuller, R K AD - Division of Clinical and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 301 EP - 305 VL - 15 SN - 0738-422X, 0738-422X KW - Index Medicus KW - United States KW - Behavior Therapy KW - Humans KW - Health Services Research KW - Alcoholism -- rehabilitation KW - Managed Care Programs KW - Outcome and Process Assessment (Health Care) KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70992520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.atitle=The+outcome+of+treatment.+Overview.&rft.au=Huebner%2C+R+B%3BFuller%2C+R+K&rft.aulast=Huebner&rft.aufirst=R&rft.date=2001-01-01&rft.volume=15&rft.issue=&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.issn=0738422X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The combination of zidovudine and interferon alpha-2B in the treatment of adult T-cell leukemia/lymphoma. AN - 70988567; 11426550 AB - Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretroviral drug zidovudine (AZT) and interferon alpha (IFNalpha) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFNalpha-2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic. crisis, acute or lymphoma type) were treated with the combination of AZT (50 - 200 mg orally 5 times a day) and IFNalpha-2b (2.5 - 10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission, lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival time after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received. JF - Leukemia & lymphoma AU - White, J D AU - Wharfe, G AU - Stewart, D M AU - Maher, V E AU - Eicher, D AU - Herring, B AU - Derby, M AU - Jackson-Booth, P G AU - Marshall, M AU - Lucy, D AU - Jain, A AU - Cranston, B AU - Hanchard, B AU - Lee, C C AU - Top, L E AU - Fleisher, T A AU - Nelson, D L AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institute, University of the West Indies, Kingston, Jamaica. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 287 EP - 294 VL - 40 IS - 3-4 SN - 1042-8194, 1042-8194 KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2b KW - 43K1W2T1M6 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Skin Tests KW - Aged KW - Neutropenia -- chemically induced KW - Adult KW - Treatment Outcome KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Maximum Tolerated Dose KW - Female KW - Male KW - Remission Induction KW - Interferon-alpha -- toxicity KW - Zidovudine -- toxicity KW - Interferon-alpha -- administration & dosage KW - Leukemia-Lymphoma, Adult T-Cell -- complications KW - Zidovudine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Leukemia-Lymphoma, Adult T-Cell -- drug therapy KW - Leukemia-Lymphoma, Adult T-Cell -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70988567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=The+combination+of+zidovudine+and+interferon+alpha-2B+in+the+treatment+of+adult+T-cell+leukemia%2Flymphoma.&rft.au=White%2C+J+D%3BWharfe%2C+G%3BStewart%2C+D+M%3BMaher%2C+V+E%3BEicher%2C+D%3BHerring%2C+B%3BDerby%2C+M%3BJackson-Booth%2C+P+G%3BMarshall%2C+M%3BLucy%2C+D%3BJain%2C+A%3BCranston%2C+B%3BHanchard%2C+B%3BLee%2C+C+C%3BTop%2C+L+E%3BFleisher%2C+T+A%3BNelson%2C+D+L%3BWaldmann%2C+T+A&rft.aulast=White&rft.aufirst=J&rft.date=2001-01-01&rft.volume=40&rft.issue=3-4&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=10428194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-21 N1 - Date created - 2001-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease. AN - 70979038; 11447832 AB - Endoplasmic reticulum (ER) appears to be a focal point for alterations that result in neuronal dysfunction and death in Alzheimer's disease (AD). Aberrant proteolytic processing and/or trafficking of the beta-amyloid precursor protein (APP) in ER may promote neuronal degeneration by increasing the levels of the neurotoxic forms of beta-amyloid (A beta) and by decreasing the levels of the neuroprotective secreted form of APP (sAPP alpha). Some cases of AD are caused by mutations in the genes encoding presenilin 1 (PS1). When expressed in cultured neuronal cells and transgenic mice, PS1 mutations cause abnormalities in ER calcium homoeostasis, enhancing the calcium responses to stimuli that activate IP3- and ryanodine-sensitive ER calcium pools. Two major consequences of this disrupted ER calcium regulation are altered proteolytic processing of APP and increased vulnerability of neurons to apoptosis and excitotoxicity. The impact of PS1 mutations and aberrant APP processing is particularly great in synaptic terminals. Perturbed synaptic calcium homoeostasis promotes activation of apoptotic cascades involving production of Par-4 (prostate apoptosis response-4), mitochondrial dysfunction and caspase activation. A beta 42 (the 42-amino-acid form of A beta) induces membrane lipid peroxidation in synapses and dendrites resulting in impairment of membrane ion-motive ATPases and glucose and glutamate transporters. This disrupts synaptic ion and energy homoeostasis thereby promoting synaptic degeneration. In contrast, sAPP alpha activates signalling pathways that protect synapses against excitotoxicity and apoptosis. In the more common sporadic forms of AD, the initiating causes of the neurodegenerative cascade are less well defined, but probably involve increased levels of oxidative stress and impaired energy metabolism. Such alterations have been shown to disrupt neuronal calcium homoeostasis in experimental models, and may therefore feed into the same neurodegenerative cascade initiated by mutations in presenilins and APP. Perturbed synaptic ER calcium homoeostasis and consequent alterations in APP processing appear to be pivotal events in both sporadic and familial forms of AD. JF - Biochemical Society symposium AU - Mattson, M P AU - Gary, D S AU - Chan, S L AU - Duan, W AD - Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Centre, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 151 EP - 162 IS - 67 SN - 0067-8694, 0067-8694 KW - Amyloid beta-Protein Precursor KW - 0 KW - Apoptosis Regulatory Proteins KW - Carrier Proteins KW - Intracellular Signaling Peptides and Proteins KW - Membrane Proteins KW - PSEN1 protein, human KW - Presenilin-1 KW - prostate apoptosis response-4 protein KW - Index Medicus KW - Animals KW - Apoptosis KW - Nerve Degeneration -- physiopathology KW - Carrier Proteins -- genetics KW - Humans KW - Protein Processing, Post-Translational KW - Amyloid beta-Protein Precursor -- metabolism KW - Membrane Proteins -- genetics KW - Amyloid beta-Protein Precursor -- genetics KW - Nerve Degeneration -- etiology KW - Synapses -- physiology KW - Nerve Degeneration -- pathology KW - Synapses -- pathology KW - Carrier Proteins -- physiology KW - Models, Neurological KW - Mutation KW - Membrane Proteins -- physiology KW - Alzheimer Disease -- physiopathology KW - Endoplasmic Reticulum -- physiology KW - Alzheimer Disease -- etiology KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70979038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Society+symposium&rft.atitle=Perturbed+endoplasmic+reticulum+function%2C+synaptic+apoptosis+and+the+pathogenesis+of+Alzheimer%27s+disease.&rft.au=Mattson%2C+M+P%3BGary%2C+D+S%3BChan%2C+S+L%3BDuan%2C+W&rft.aulast=Mattson&rft.aufirst=M&rft.date=2001-01-01&rft.volume=&rft.issue=67&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+symposium&rft.issn=00678694&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-14 N1 - Date created - 2001-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategies for the treatment of cancer pain in the new millennium. AN - 70976734; 11434451 AB - As was the case in the era before us, in the new millennium we will continue to see an abundance of patients experiencing cancer-related pain for different reasons. Although much needless pain and suffering still affects many of those with cancer, we are presented with a medical dichotomy. With the analgesic drugs available today, and the relatively simple and effective guidelines to treat cancer pain published and disseminated by the World Health Organization, why do people with cancer continue to experience pain? As we search for the answer, the horizon may hold promising new drugs, 'old drugs' with new interest and applications, and new strategies for the field of pain therapy. Possibilities include the isolation and development of analgesics or analgesic combinations that may minimise the adverse effects which are often associated with the current therapeutic class of opioid analgesics. In addition, current research points to promising results identifying the N-methyl D-aspartate non-opioid receptor as a likely component of neuropathic pain. Drugs such as gabapentin, the mechanism of action of which is not well known, have found favour within the clinical community for their analgesic properties and good tolerability. Methadone, in a phase of resurgence, has garnered the attention of the clinical community because of its unique receptor activity and pharmacoeconomic benefits. A number of clinical studies have demonstrated that methadone has a valuable role in treating cancer pain. Perhaps, an unbalanced focus on the risks of inappropriate use, rather than the benefits, should not compromise or distract from the use of methadone as an alternative to morphine. Studies are on going to assess the potential role of methadone in treating neuropathic pain. Drugs such as cannabinoids, although currently applicable for patients with anorexia, nausea and/or vomiting, may offer benefits to patients experiencing pain. Other opportunities exist with such compounds as alpha2-adrenergic agonists, nicotine, lidocaine and ketamine. New strategies such as the switching opioids and/or their route of administration may offer improved analgesia with fewer adverse effects, thus providing therapeutic alternatives for the clinical community. In addition, there is interest in the co-administration of opioids that act on different receptors. For instance, oxycodone appears to be a kappa opioid receptor agonist and may offer enhanced analgesia when combined with morphine. JF - Drugs AU - Ripamonti, C AU - Dickerson, E D AD - Rehabilitation and Palliative Care Division, National Cancer Institute of Milan, Italy. ripamonti@istitutotumori.mi.it Y1 - 2001 PY - 2001 DA - 2001 SP - 955 EP - 977 VL - 61 IS - 7 SN - 0012-6667, 0012-6667 KW - Analgesics, Opioid KW - 0 KW - Cannabinoids KW - Nicotine KW - 6M3C89ZY6R KW - Morphine KW - 76I7G6D29C KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Drug Therapy, Combination KW - Nicotine -- therapeutic use KW - Dose-Response Relationship, Drug KW - Humans KW - Cannabinoids -- therapeutic use KW - Pain -- etiology KW - Pain -- drug therapy KW - Neoplasms KW - Morphine -- therapeutic use KW - Methadone -- therapeutic use KW - Morphine -- adverse effects KW - Analgesics, Opioid -- therapeutic use KW - Methadone -- administration & dosage KW - Analgesics, Opioid -- adverse effects KW - Analgesics, Opioid -- administration & dosage KW - Morphine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70976734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs&rft.atitle=Strategies+for+the+treatment+of+cancer+pain+in+the+new+millennium.&rft.au=Ripamonti%2C+C%3BDickerson%2C+E+D&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=2001-01-01&rft.volume=61&rft.issue=7&rft.spage=955&rft.isbn=&rft.btitle=&rft.title=Drugs&rft.issn=00126667&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Real-time and quantitative PCR: applications to mechanism-based toxicology. AN - 70958046; 11424221 AB - There is increasing awareness that quantitative analysis of changes in molecular targets plays a key role in addressing scientific questions in molecular toxicology, molecular epidemiology, and human risk assessment. One of the emerging technologies that is being used to analyze these molecular targets is real-time and quantitative (RTAQ) polymerase chain reaction (PCR). The aim of this review is to provide the reader with an overview of this technology and to highlight specific applications of this technology to some key areas of molecular toxicology. Copyright 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:121-127, 2001 JF - Journal of biochemical and molecular toxicology AU - Walker, N J AD - Molecular Epidemiology and Dosimetry Section, Laboratory of Computational Biology and Risk Analysis, NIEHS, 111 Alexander Drive, PO Box 12233, MD D4-01, Research Triangle Park, NC 27709, USA. walker3@niehs.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 121 EP - 127 VL - 15 IS - 3 SN - 1095-6670, 1095-6670 KW - Fluorescent Dyes KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Models, Biological KW - Risk Assessment KW - Fluorescent Dyes -- metabolism KW - Polymerase Chain Reaction -- methods KW - Toxicology -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70958046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+and+molecular+toxicology&rft.atitle=Real-time+and+quantitative+PCR%3A+applications+to+mechanism-based+toxicology.&rft.au=Walker%2C+N+J&rft.aulast=Walker&rft.aufirst=N&rft.date=2001-01-01&rft.volume=15&rft.issue=3&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+and+molecular+toxicology&rft.issn=10956670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-27 N1 - Date created - 2001-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct separation of in vivo and in vitro am3 revertants in transgenic mice carrying the phiX174 am3, cs70 vector. AN - 70949358; 11424185 AB - Target genes in most transgenic systems have higher spontaneous mutation frequencies than do endogenous mammalian genes. Spontaneous mutations in transgenes predominantly arise from three sources: (1) mutations fixed in the animals, (2) mutations arising from replication errors caused by damage to the DNA that may have occurred in vivo or in vitro and then was fixed during amplification of the vector in vitro, and (3) mutations arising during replication of non-revertant phages in non-permissive bacteria. An assay based on single bursts was developed to directly distinguish between the in vivo and in vitro origins of revertants. The size of the aliquot is determined by mutant frequency and is adjusted so that ideally no more than 10 to 20% of the aliquots contain a bacterial cell transformed with a mutant phage. Mutations are detected as revertants of an amber mutation (am3) in phiX174 am3, cs70. The minimum burst size of non-revertant phiX am3, cs70 from splenic DNA on a permissive bacterial strain was larger than 30 plaque-forming units (pfu). Based on this observation, a burst size of 31 plaque-forming revertants was chosen as the minimum burst size of a fixed mutation. The single burst assay was tested on DNA from spleens of animals that were treated with 150 mg/kg 1-ethyl-1 nitrosurea. Only the fraction of aliquots with single bursts of revertants (> 30) increased in the treated animals compared to the controls. In contrast, there was no difference between treated and control animals for revertant frequencies calculated for burst sizes 30 pfu). Total average revertant frequency measured in DNA from treated animals was less than twofold more than the average spontaneous frequency (P = 0.048). When frequencies were based on burst sizes >30, there was a 4.6-fold increase among treated animals compared with controls (P = 0.026). The single burst-assay resulted in a more sensitive test for mutagenicity because it eliminated noise from in-vitro mutations. JF - Environmental and molecular mutagenesis AU - Malling, H V AU - Delongchamp, R R AD - Mammalian Mutagenesis Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute Of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. malling@niehs.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 345 EP - 355 VL - 37 IS - 4 SN - 0893-6692, 0893-6692 KW - DNA Adducts KW - 0 KW - Mutagens KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Spleen -- metabolism KW - Transformation, Genetic KW - Genetic Vectors KW - Transgenes KW - Mice KW - Mice, Transgenic KW - Mutation KW - DNA Mutational Analysis -- methods KW - Bacteriophage phi X 174 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70949358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Direct+separation+of+in+vivo+and+in+vitro+am3+revertants+in+transgenic+mice+carrying+the+phiX174+am3%2C+cs70+vector.&rft.au=Malling%2C+H+V%3BDelongchamp%2C+R+R&rft.aulast=Malling&rft.aufirst=H&rft.date=2001-01-01&rft.volume=37&rft.issue=4&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-09 N1 - Date created - 2001-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Quality control of spirometric tests used in health surveillance for occupational exposure risk, in the province of Viterbo]. TT - Controllo di qualità delle prove spirometriche eseguite nell'ambito della sorveglianza sanitaria per esposizione a rischio lavorativo, in provincia di Viterbo. AN - 70860959; 11367827 AB - A quality control survey on spirometry assessments carried out in a number of factories in the province of Viterbo (Lazio Region) was made by the Local Health Unit in Viterbo, as required by law 626/94 on the promotion of workers health. The survey concerned 734 measurements concerning the same number of employees from 29 different factories. Each spirometry assessment was repeated in this study according to the quality standards defined in the literature and our own results were compared with the values which had been obtained over one year during the health surveillance program (ASP). A few main functional parameters were considered according to the following criteria: percentage of agreement (tolerance +/- 5%) between the two FVC, FEV1 and FEF25-75 measures or degree of discrepancy; for FEV1/FVC ratio, the occurrence of 90 values (reflecting poor reliability in the measurement of the lung volumes) in the two sets of data. Further criteria concerned the comparison of the height of the individuals (tolerance range +/- 1 cm), and the comparison of the overall spirometry rating expressed as the number of tests rated normal or abnormal (during the first assessment as compared to the second). The results show poor agreement (11.4%) for FVC with as many as 85.8% underestimated values; 30.1% agreement and 64.2% underestimate for FEV1; 17% agreement and 53.5% overestimate for FEF25-75. There were 6.5% fewer 90 ratios in the tests carried out in the factories as compared to our own. There was 32.9% agreement on the height, with overestimation in 63.7% of the cases. There were 12.3% "false abnormal" and 2.6% "false normal" results in the overall rating of the spirometry (as carried out by the factories compared to our own). In conclusion, the survey revealed a trend in the measurements carried out by the factories to underestimate the volumes, overestimate the flows, improperly select the theoretical reference values because of a mistake in measuring the height, to overestimate restrictive abnormalities, and underestimate the obstructive ones. JF - La Medicina del lavoro AU - Valenti, E AU - Manzari, G AU - De Angelis, V AU - Ercolani, S AU - Liberati, A AU - Capitta, C AU - Mancini, G AU - Scrocchia, I AU - Quercia, A AD - Servizio di Prevenzione, Igiene e Sicurezza nei Luoghi di Lavoro, A.S.L. Viterbo, Via Ferretti 169, 01033 Civita Castellana. spisllcc@tin.it PY - 2001 SP - 5 EP - 11 VL - 92 IS - 1 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Adult KW - Forced Expiratory Volume KW - Quality Control KW - Italy KW - Occupational Exposure KW - Spirometry -- standards KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70860959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BQuality+control+of+spirometric+tests+used+in+health+surveillance+for+occupational+exposure+risk%2C+in+the+province+of+Viterbo%5D.&rft.au=Valenti%2C+E%3BManzari%2C+G%3BDe+Angelis%2C+V%3BErcolani%2C+S%3BLiberati%2C+A%3BCapitta%2C+C%3BMancini%2C+G%3BScrocchia%2C+I%3BQuercia%2C+A&rft.aulast=Valenti&rft.aufirst=E&rft.date=2001-01-01&rft.volume=92&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-06 N1 - Date created - 2001-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New approaches to the understanding of the molecular basis of oral cancer. AN - 70844250; 11349962 AB - Cancers of the oral cavity, salivary glands, larynx, and pharynx, collectively referred to as squamous cell carcinomas of the head and neck (HNSCC), are the sixth most common cancer among men in the developed world. The prognosis of HNSCC patients is still poor, which reflects the fact that although the risk factors for HNSCC are well-recognized, very little is known about the molecular mechanisms responsible for this malignancy. This review describes some of the current efforts and technological advances that have focused on the creation of a complete information infrastructure for genes expressed during squamous cell carcinogenesis. These include: the recently described HNSCC-specific chromosomal alterations (cCAP); the Head and Neck Cancer Genome Anatomy Project (HN-CGAP), whose goal is the systematic identification and cataloguing of known and novel genes expressed during tumor development; and the use of laser-capture microdissection (LCM), which is pivotal for the comprehensive molecular characterization of normal, pre-cancerous, and malignant cells by means of DNA-array technology. The latter provides the means for the analysis of expression patterns of thousands of genes simultaneously. The use of LCM for proteomics and DNA analysis is also included in this review. These revolutionary approaches are likely to have an unprecedented impact on cancer biology, and provide exciting opportunities to unravel the still-unknown mechanisms involved in squamous cell carcinogenesis. They are also expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of preneoplastic lesions, as well as novel targets for pharmacological intervention in this disease. JF - Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists AU - Patel, V AU - Leethanakul, C AU - Gutkind, J S AD - Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 55 EP - 63 VL - 12 IS - 1 SN - 1045-4411, 1045-4411 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - Dentistry KW - Index Medicus KW - United States KW - Proto-Oncogenes -- physiology KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - National Institutes of Health (U.S.) KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Chromosome Aberrations KW - Genes, Tumor Suppressor -- physiology KW - DNA, Neoplasm -- analysis KW - Neoplasm Proteins -- analysis KW - Genomic Library KW - Gene Expression Regulation, Neoplastic KW - Carcinoma, Squamous Cell -- genetics KW - Head and Neck Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70844250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oral+biology+and+medicine+%3A+an+official+publication+of+the+American+Association+of+Oral+Biologists&rft.atitle=New+approaches+to+the+understanding+of+the+molecular+basis+of+oral+cancer.&rft.au=Patel%2C+V%3BLeethanakul%2C+C%3BGutkind%2C+J+S&rft.aulast=Patel&rft.aufirst=V&rft.date=2001-01-01&rft.volume=12&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oral+biology+and+medicine+%3A+an+official+publication+of+the+American+Association+of+Oral+Biologists&rft.issn=10454411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-20 N1 - Date created - 2001-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of common genetic polymorphisms to enhance the epidemiologic study of environmental carcinogens. AN - 70843179; 11342183 AB - Overwhelming evidence indicates that environmental exposures, broadly defined, are responsible for most cancer. There is reason to believe, however, that relatively common polymorphisms in a wide spectrum of genes may modify the effect of these exposures. We discuss the rationale for using common polymorphisms to enhance our understanding of how environmental exposures cause cancer and comment on epidemiologic strategies to assess these effects, including study design, genetic and statistical analysis, and sample size requirements. Special attention is given to sources of potential bias in population studies of gene--environment interactions, including exposure and genotype misclassification and population stratification (i.e., confounding by ethnicity). Nevertheless, by merging epidemiologic and molecular approaches in the twenty-first century, there will be enormous opportunities for unraveling the environmental determinants of cancer. In particular, studies of genetically susceptible subgroups may enable the detection of low levels of risk due to certain common exposures that have eluded traditional epidemiologic methods. Further, by identifying susceptibility genes and their pathways of action, it may be possible to identify previously unsuspected carcinogens. Finally, by gaining a more comprehensive understanding of environmental and genetic risk factors, there should emerge new clinical and public health strategies aimed at preventing and controlling cancer. JF - Biochimica et biophysica acta AU - Rothman, N AU - Wacholder, S AU - Caporaso, N E AU - Garcia-Closas, M AU - Buetow, K AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA. rothmann@epndce.nci.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - C1 EP - 10 VL - 1471 IS - 2 SN - 0006-3002, 0006-3002 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Animals KW - Molecular Epidemiology KW - Models, Genetic KW - Humans KW - Environmental Exposure KW - Models, Statistical KW - Genetic Predisposition to Disease KW - Epidemiologic Research Design KW - Carcinogens, Environmental -- adverse effects KW - Polymorphism, Genetic KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Carcinogens, Environmental -- toxicity KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70843179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=The+use+of+common+genetic+polymorphisms+to+enhance+the+epidemiologic+study+of+environmental+carcinogens.&rft.au=Rothman%2C+N%3BWacholder%2C+S%3BCaporaso%2C+N+E%3BGarcia-Closas%2C+M%3BBuetow%2C+K%3BFraumeni%2C+J+F&rft.aulast=Rothman&rft.aufirst=N&rft.date=2001-01-01&rft.volume=1471&rft.issue=2&rft.spage=C1&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structurally related nucleotides as selective agonists and antagonists at P2Y1 receptors. AN - 70839875; 11347970 AB - The P2Y1 receptor responds to adenine nucleotides and is present in platelets, heart, smooth muscles prostate, ovary, and brain. A selective antagonist may be useful as an antithrombotic agent. We have analyzed the binding site of this G protein-coupled receptor using ligand design, site-directed mutagenesis, and homology modeling based on rhodopsin. We have designed and synthesized a series of deoxyadenosine 3',5'-bisphosphate derivatives that act as antagonists, or, in some cases with small structural changes, as agonists or partial agonists. The 2-position accommodates Cl or thioethers, whereas the N6-position is limited to Me or Et. 2'-Substitution with OH or OMe increases agonist efficacy over 2'-H. Using molecular modeling of the binding site, the oxygen atoms of the ribose moiety were predicted to be non-essential, i.e. no specific H-bonds with the receptor protein appear in the model. We have, therefore, substituted this moiety with carbocylics, smaller and larger rings, conformationally constrained rings, and acyclics, with retention of affinity for the receptor. With simplified pharmacophores we are exploring the steric and electronic requirements of the receptor binding site, and the structural basis of receptor activation. JF - Farmaco (Societa chimica italiana : 1989) AU - Jacobson, K A AU - Moro, S AU - Hoffmann, C AU - Kim, Y C AU - Kim, H S AU - Ravi, R G AU - Harden, T K AU - Boyer, J L AD - Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892-0810, USA. kajacobs@helix.nih.gov PY - 2001 SP - 71 EP - 75 VL - 56 IS - 1-2 SN - 0014-827X, 0014-827X KW - Nucleotides KW - 0 KW - P2RY1 protein, human KW - Purinergic P2 Receptor Agonists KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Index Medicus KW - Humans KW - Molecular Conformation KW - Structure-Activity Relationship KW - Binding Sites KW - Receptors, Purinergic P2 -- drug effects KW - Nucleotides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70839875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Farmaco+%28Societa+chimica+italiana+%3A+1989%29&rft.atitle=Structurally+related+nucleotides+as+selective+agonists+and+antagonists+at+P2Y1+receptors.&rft.au=Jacobson%2C+K+A%3BMoro%2C+S%3BHoffmann%2C+C%3BKim%2C+Y+C%3BKim%2C+H+S%3BRavi%2C+R+G%3BHarden%2C+T+K%3BBoyer%2C+J+L&rft.aulast=Jacobson&rft.aufirst=K&rft.date=2001-01-01&rft.volume=56&rft.issue=1-2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Farmaco+%28Societa+chimica+italiana+%3A+1989%29&rft.issn=0014827X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of the varicella-zoster virus genome: lessons learned. AN - 70830055; 11339555 AB - The varicella-zoster virus (VZV) genome encodes at least 70 genes. We have developed a cosmid based system to inactivate individual viral genes or to insert foreign genes into the genome. We have shown that many VZV genes are not required for replication of the virus in cell culture. Several of these genes, including VZV ORF61, ORF47, and ORF10, have unexpected phenotypes in cell culture and differ from their homologs in the better studied herpes simplex virus (HSV). We have also used the Oka strain of VZV as a live virus vaccine vector. Guinea pigs vaccinated with recombinant VZV expressing HSV-2 glycoprotein D and challenged with HSV-2 have reduced severity of primary genital herpes and reduced mortality compared to animals receiving parental VZV. Recently we have inserted the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) glycoprotein 160 genes into the Oka strain of VZV and have shown that these proteins are expressed in recombinant virus-infected cells. Thus, directed mutagenesis of the VZV genome is providing new insights into viral pathogenesis and may provide new candidate vaccines. JF - Archives of virology. Supplementum AU - Cohen, J I AD - Medical Virology Section, Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 91 EP - 97 IS - 17 SN - 0939-1983, 0939-1983 KW - ORF 10 protein, varicella-zoster virus KW - 0 KW - Trans-Activators KW - Viral Proteins KW - Viral Vaccines KW - protein 61, Varicella-zoster virus KW - 106121-63-5 KW - Protein Kinases KW - EC 2.7.- KW - Varicella-Zoster ORF47-associated protein kinase KW - EC 2.7.1.- KW - Index Medicus KW - Viral Proteins -- genetics KW - Animals KW - Protein Kinases -- physiology KW - Trans-Activators -- genetics KW - Humans KW - Genetic Vectors KW - Protein Kinases -- genetics KW - Trans-Activators -- physiology KW - Viral Proteins -- physiology KW - Mutagenesis KW - Herpesvirus 3, Human -- genetics KW - Genome, Viral KW - Herpesvirus 3, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70830055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+virology.+Supplementum&rft.atitle=Mutagenesis+of+the+varicella-zoster+virus+genome%3A+lessons+learned.&rft.au=Cohen%2C+J+I&rft.aulast=Cohen&rft.aufirst=J&rft.date=2001-01-01&rft.volume=&rft.issue=17&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Archives+of+virology.+Supplementum&rft.issn=09391983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-06-07 N1 - Date created - 2001-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic drug monitoring in methadone maintenance: choosing a matrix. AN - 70792654; 11318398 AB - Methadone maintenance is the premier pharmacological treatment for opioid addiction, but it is rarely informed by evidence-based practice guidelines for dosage monitoring and adjustment. Such guidelines are crucial because the pharmacokinetics of methadone vary greatly among patients, and this variation may account for differences in treatment outcome. We review the pharmacokinetics of methadone and factors that may alter it (including drug interactions, disease states, and idiosyncratic differences among patients). Also reviewed are prospects for therapeutic drug monitoring (TDM) of methadone in plasma, urine, sweat, and saliva. Due to its ease of collection and its presumed representation of the bioavailable free-fraction of methadone, saliva may be a promising matrix. However, saliva methadone concentrations are influenced by salivary pH, and future studies are needed to determine how to control for that. Administrative, medical, and social implications of methadone TDM are briefly discussed. JF - Journal of addictive diseases AU - Moolchan, E T AU - Umbricht, A AU - Epstein, D AD - Department of Health and Human Services, National Institute of Health, National Institute of Drug Abuse, Baltimore, MD 21224, USA. emoolcha@intra.nida.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 55 EP - 73 VL - 20 IS - 2 SN - 1055-0887, 1055-0887 KW - Narcotics KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Drug Interactions KW - Sweat -- metabolism KW - Mixed Function Oxygenases -- metabolism KW - Half-Life KW - Humans KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Saliva -- metabolism KW - Male KW - Female KW - Methadone -- therapeutic use KW - Drug Monitoring KW - Narcotics -- therapeutic use KW - Narcotics -- metabolism KW - Methadone -- pharmacokinetics KW - Opioid-Related Disorders -- rehabilitation KW - Narcotics -- pharmacokinetics KW - Methadone -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70792654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+addictive+diseases&rft.atitle=Therapeutic+drug+monitoring+in+methadone+maintenance%3A+choosing+a+matrix.&rft.au=Moolchan%2C+E+T%3BUmbricht%2C+A%3BEpstein%2C+D&rft.aulast=Moolchan&rft.aufirst=E&rft.date=2001-01-01&rft.volume=20&rft.issue=2&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Journal+of+addictive+diseases&rft.issn=10550887&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Amotivational syndrome in organic solvent abusers]. AN - 70678613; 11233295 AB - Amotivational syndrome is a chronic psychiatric disorder characterized by a variety of changes in personality, emotions and cognitive functions such as lack of activity, inward-turning, avolition, apathy, incoherence, blunted affect, inability to concentrate and memory disturbance. The syndrome was first described among those patients with a history of longtime cannabis use in the 1960's. Since then, there have been several reports describing similar psychiatric disorders to amotivational syndrome among patients with the history of some other psychoactive substances use including solvents, methamphetamine and OTC cough syrups. Therefore, the syndrome has been recognized as one of the common psychiatric conditions that might develop in patients with a history of any psychoactive substance use. Recently, more attention has been paid to the biological basis of amotivational syndrome. Several studies using MRI, SPECT or neuropsychological measures have revealed white matter changes, hypoperfusion in the frontal cortex of the brain and impairment of frontal lobe function. Those findings suggest that amotivational syndrome might be related to "hypofrontality" of the brain. Although no specific treatments have been reported to be definitely effective for patients with amotivational syndrome, some neuroleptics with activating properties or antidepressants can be given appropriately to treat the chief symptoms of the patients. JF - Nihon yakurigaku zasshi. Folia pharmacologica Japonica AU - Ozaki, S AU - Wada, K AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa-shi, Chiba-ken 272-0827, Japan. ozaki@ncnp-k.go.jp Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 42 EP - 48 VL - 117 IS - 1 SN - 0015-5691, 0015-5691 KW - Antidepressive Agents KW - 0 KW - Antipsychotic Agents KW - Solvents KW - Index Medicus KW - Frontal Lobe -- pathology KW - Syndrome KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Antidepressive Agents -- therapeutic use KW - Atrophy KW - Neuropsychological Tests KW - Motivation KW - Substance-Related Disorders -- pathology KW - Substance-Related Disorders -- drug therapy KW - Solvents -- adverse effects KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70678613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+yakurigaku+zasshi.+Folia+pharmacologica+Japonica&rft.atitle=%5BAmotivational+syndrome+in+organic+solvent+abusers%5D.&rft.au=Ozaki%2C+S%3BWada%2C+K&rft.aulast=Ozaki&rft.aufirst=S&rft.date=2001-01-01&rft.volume=117&rft.issue=1&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Nihon+yakurigaku+zasshi.+Folia+pharmacologica+Japonica&rft.issn=00155691&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioural, histological and immunocytochemical consequences following 192 IgG-saporin immunolesions of the basal forebrain cholinergic system. AN - 70655166; 11226712 AB - Use of the selective immunotoxin; 192 IgG-saporin, is helping to elucidate the role of the cholinergic system in cognition by overcoming the problems of interpretation associated with the use of non-specific lesioning agents. In separate studies, we have compared the long- and short-term effects of single site and combined saporin lesions of the nucleus basalis magnocellularis and medial septal area, on spatial learning and memory in radial arm and water maze tasks. At 11 months, only rats with combined lesions showed deficits in both radial and water maze tasks, although terminal cholinergic deafferentation was substantial and extensive tissue loss was seen at the injection sites in both single and combined lesions. However, the extensive tissue loss with long-term lesions suggested that behavioural deficits were not solely attributable to cholinergic deafferentation. In contrast, when rats with combined lesions were tested 5 months after lesioning, no deficits were apparent, although there was almost complete loss of choline acetyltransferase- and nerve growth factor receptor-immunoreactivity in the basal forebrain with no tissue damage at the injection sites. This study supports existing literature that selective loss of cholinergic neurons in the basal forebrain does not produce behavioural impairments in standard tasks of learning and memory, but deficits are apparent when damage is non-selective as occurs late after lesioning, confounding interpretation of behavioural data. It further highlights potential problems with this immunotoxin in long-term studies. JF - Brain research bulletin AU - Perry, T AU - Hodges, H AU - Gray, J A AD - Department of Psychology, Institute of Psychiatry, King's College London, London, United Kingdom. perryt@grc.nia.nih.gov Y1 - 2001/01/01/ PY - 2001 DA - 2001 Jan 01 SP - 29 EP - 48 VL - 54 IS - 1 SN - 0361-9230, 0361-9230 KW - 192 IgG-saporin KW - 0 KW - Antibodies KW - Antibodies, Monoclonal KW - Biomarkers KW - Cholinergic Agents KW - Glial Fibrillary Acidic Protein KW - Immunotoxins KW - Receptor, Nerve Growth Factor KW - Ribosome Inactivating Proteins, Type 1 KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Acetylcholinesterase KW - EC 3.1.1.7 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Maze Learning -- physiology KW - Calcium -- analysis KW - Receptor, Nerve Growth Factor -- analysis KW - Choline O-Acetyltransferase -- immunology KW - Cerebral Cortex -- physiopathology KW - Rats KW - Glial Fibrillary Acidic Protein -- immunology KW - Cerebral Cortex -- pathology KW - Septal Nuclei -- pathology KW - Glial Fibrillary Acidic Protein -- analysis KW - Hippocampus -- physiopathology KW - Acetylcholinesterase -- analysis KW - Male KW - Receptor, Nerve Growth Factor -- immunology KW - Cell Count KW - Choline O-Acetyltransferase -- analysis KW - Memory -- physiology KW - Septal Nuclei -- physiopathology KW - Rats, Sprague-Dawley KW - Locomotion -- physiology KW - Hippocampus -- pathology KW - Immunohistochemistry KW - Cholinergic Fibers -- enzymology KW - Cholinergic Fibers -- pathology KW - Nerve Degeneration -- physiopathology KW - Nerve Degeneration -- pathology KW - Cholinergic Fibers -- chemistry KW - Behavior, Animal -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70655166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research+bulletin&rft.atitle=Behavioural%2C+histological+and+immunocytochemical+consequences+following+192+IgG-saporin+immunolesions+of+the+basal+forebrain+cholinergic+system.&rft.au=Perry%2C+T%3BHodges%2C+H%3BGray%2C+J+A&rft.aulast=Perry&rft.aufirst=T&rft.date=2001-01-01&rft.volume=54&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Brain+research+bulletin&rft.issn=03619230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical modulation of 5-FU in systemic treatment of advanced colorectal cancer. AN - 70654320; 11219972 AB - Randomized studies have tested a variety of strategies to improve the activity of 5-fluorouracil (5-FU) in colorectal cancer patients. Results from 14 randomized trials comparing 5-FU administered via intravenous (i.v.) bolus either as a single agent or modulated by leucovorin indicate a significantly higher response rate with 5-FU/leucovorin (25% vs 13% of assessable patients). Sequential methotrexate followed by i.v. bolus 5-FU is associated with a higher response rate. Continuous infusion schedules also produce superior response rates compared to bolus 5-FU alone. Published meta-analyses indicate a small, but statistically significant, survival advantage for methotrexate/5-FU and infusional 5-FU, but not for leucovorin-modulated 5-FU. Although the incidence of hand-foot syndrome is higher with protracted infusional 5-FU, the incidence of other toxicities including myelosuppression, diarrhea, and mucositis is low. Oral administration of 5-FU may simulate infusional schedules while avoiding catheter-related complications. JF - Oncology (Williston Park, N.Y.) AU - Grem, J L AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland, USA. jgrem@helix.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 13 EP - 19 VL - 15 IS - 1 Suppl 2 SN - 0890-9091, 0890-9091 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Randomized Controlled Trials as Topic KW - Infusions, Intra-Arterial KW - Injections, Intravenous KW - Infusions, Intravenous KW - Leucovorin -- administration & dosage KW - Humans KW - Drug Synergism KW - Methotrexate -- administration & dosage KW - Meta-Analysis as Topic KW - Colorectal Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70654320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+%28Williston+Park%2C+N.Y.%29&rft.atitle=Biochemical+modulation+of+5-FU+in+systemic+treatment+of+advanced+colorectal+cancer.&rft.au=Grem%2C+J+L&rft.aulast=Grem&rft.aufirst=J&rft.date=2001-01-01&rft.volume=15&rft.issue=1+Suppl+2&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Oncology+%28Williston+Park%2C+N.Y.%29&rft.issn=08909091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surrogate end-point biomarkers in chemopreventive drug development. AN - 70652556; 11220652 AB - Relevant and feasible surrogate end-points are needed for the evaluation of intervention strategies against cancer and other chronic, life-threatening diseases. Carcinogenesis can be viewed as a process of progressive disorganization. This process is characterized by the accumulation of genotypic lesions and corresponding tissue and cellular abnormalities, including loss of proliferation and apoptosis controls. Potential surrogate end-points for cancer incidence include both phenotypic and genotypic biomarkers of this progression. In the US National Cancer Institute chemoprevention programme, histological modulation of a precancer (intraepithelial neoplasia) has so far been the primary phenotypic surrogate end-point in chemoprevention trials. Additionally, high priority has been given to biomarkers measuring specific and general genotypic changes correlated with the carcinogenesis progression model for the targeted cancer (e.g., progressive genomic instability as measured by loss of heterozygosity or amplification at specific microsatellite loci). Other potential surrogate end-points include proliferation and differentiation indices, specific gene and general chromosome damage, cell growth regulatory molecules, and biochemical activities (e.g., enzyme inhibition). Serum biomarkers thought to be associated with cancer progression (e.g., prostate-specific antigen) are particularly appealing surrogate end-points because of accessibility. Potentially chemopreventive effects of the test agent may also be measured (e.g., tissue and serum estrogen levels in studies of steroid aromatase inhibitors). To establish chemopreventive efficacy, prevention of virtually all biomarker lesions, or of those lesions with particular propensity for progression, may be required. Ideally, the phenotype and genotype of any new or remaining precancers in the target tissue of chemopreventive agent-treated subjects would show less, and certainly no greater, potential for progression than those of placebo-treated subjects. JF - IARC scientific publications AU - Kelloff, G J AU - Sigman, C C AU - Hawk, E T AU - Johnson, K M AU - Crowell, J A AU - Guyton, K Z AD - National Cancer Institute, Division of Cancer Prevention, Bethesda, MD 20892-7322, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 13 EP - 26 VL - 154 SN - 0300-5038, 0300-5038 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - Biomarkers, Tumor KW - Index Medicus KW - Models, Genetic KW - Humans KW - Precancerous Conditions -- diagnosis KW - Patient Selection KW - Precancerous Conditions -- epidemiology KW - Biomarkers, Tumor -- genetics KW - Anticarcinogenic Agents -- therapeutic use KW - Drug Evaluation -- methods KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70652556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Surrogate+end-point+biomarkers+in+chemopreventive+drug+development.&rft.au=Kelloff%2C+G+J%3BSigman%2C+C+C%3BHawk%2C+E+T%3BJohnson%2C+K+M%3BCrowell%2C+J+A%3BGuyton%2C+K+Z&rft.aulast=Kelloff&rft.aufirst=G&rft.date=2001-01-01&rft.volume=154&rft.issue=&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. AN - 70651115; 11181997 AB - In a phase III trial, 191 patients aged over 70 with stage IIIB/IV non-small cell lung cancer were randomized to receive best supportive care (BSC) alone or BSC plus vinorelbine on days 1 and 8, q 21 days for up to six cycles. Increasing difficulties in recruitment meant that the investigators, blinded to the results, stopped the trial early. Data from 161 patients have been analyzed. The vinorelbine regimen was well tolerated. Grade 3/4 neutropenia occurred in 10% of patients and grade 2/3 anemia in 16%. The principle nonhematological toxicities were constipation and fatigue. An objective response rate was recorded in 19.7% of the 76 patients treated with vinorelbine. The survival experience of these patients was significantly superior to that among control patients. The median duration of survival was longer (28 versus 21 weeks) and patients receiving vinorelbine were significantly more likely to survive to one year (32% versus 14%). The relative risk of death in the vinorelbine group was 0.65 (95% confidence interval: 0.45-0.93). Quality of life was extensively investigated using European Organization for Research and Treatment of Cancer scales. While aspects of quality-of-life issues that were directly related to drug toxicity (such as nausea and constipation) were lower in the vinorelbine group, patients who received vinorelbine fared better than controls on measures related to lung cancer symptoms and pain and on social, cognitive, and physical functioning. JF - The oncologist AU - Gridelli, C AD - National Cancer Institute, Division of Medical Oncology B, Naples, Italy. cgridelli@sirio-oncology.it Y1 - 2001 PY - 2001 DA - 2001 SP - 4 EP - 7 VL - 6 Suppl 1 SN - 1083-7159, 1083-7159 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Vinblastine KW - 5V9KLZ54CY KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Age Factors KW - Aged, 80 and over KW - Humans KW - Treatment Outcome KW - Quality of Life KW - Neutropenia -- chemically induced KW - Aged KW - Male KW - Female KW - Survival Analysis KW - Vinblastine -- therapeutic use KW - Vinblastine -- analogs & derivatives KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70651115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=The+ELVIS+trial%3A+a+phase+III+study+of+single-agent+vinorelbine+as+first-line+treatment+in+elderly+patients+with+advanced+non-small+cell+lung+cancer.+Elderly+Lung+Cancer+Vinorelbine+Italian+Study.&rft.au=Gridelli%2C+C&rft.aulast=Gridelli&rft.aufirst=C&rft.date=2001-01-01&rft.volume=6+Suppl+1&rft.issue=&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=10837159&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Composite active site of an ABC ATPase: MutS uses ATP to verify mismatch recognition and authorize DNA repair. AN - 70646627; 11172706 AB - The MutS protein initiates DNA mismatch repair by recognizing mispaired and unpaired bases embedded in duplex DNA and activating endo- and exonucleases to remove the mismatch. Members of the MutS family also possess a conserved ATPase activity that belongs to the ATP binding cassette (ABC) superfamily. Here we report the crystal structure of a ternary complex of MutS-DNA-ADP and assays of initiation of mismatch repair in conjunction with perturbation of the composite ATPase active site by mutagenesis. These studies indicate that MutS has to bind both ATP and the mismatch DNA simultaneously in order to activate the other mismatch repair proteins. We propose that the MutS ATPase activity plays a proofreading role in DNA mismatch repair, verification of mismatch recognition, and authorization of repair. JF - Molecular cell AU - Junop, M S AU - Obmolova, G AU - Rausch, K AU - Hsieh, P AU - Yang, W AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 1 EP - 12 VL - 7 IS - 1 SN - 1097-2765, 1097-2765 KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - MutL protein, E coli KW - Nucleic Acid Heteroduplexes KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Endodeoxyribonucleases KW - EC 3.1.- KW - methyl-directed mismatch repair protein, E coli KW - EC 3.1.21.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - MutL Proteins KW - EC 3.6.1.3 KW - MutS DNA Mismatch-Binding Protein KW - MutS protein, E coli KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Protein Structure, Secondary KW - Enzyme Activation KW - ATP-Binding Cassette Transporters -- metabolism KW - Humans KW - Nucleic Acid Heteroduplexes -- chemistry KW - DNA-Binding Proteins -- genetics KW - Endodeoxyribonucleases -- genetics KW - Endodeoxyribonucleases -- metabolism KW - Hydrolysis KW - Nucleic Acid Heteroduplexes -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - Crystallography KW - Protein Binding -- genetics KW - Binding Sites -- genetics KW - Protein Structure, Tertiary KW - DNA-Binding Proteins -- metabolism KW - DNA Repair -- genetics KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Bacterial Proteins -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Base Pair Mismatch -- genetics KW - Adenosine Triphosphate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70646627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cell&rft.atitle=Composite+active+site+of+an+ABC+ATPase%3A+MutS+uses+ATP+to+verify+mismatch+recognition+and+authorize+DNA+repair.&rft.au=Junop%2C+M+S%3BObmolova%2C+G%3BRausch%2C+K%3BHsieh%2C+P%3BYang%2C+W&rft.aulast=Junop&rft.aufirst=M&rft.date=2001-01-01&rft.volume=7&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1FW6; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of CD8+ cytotoxic T lymphocyte/tumor cell interactions reflecting recognition of an endogenously expressed murine wild-type p53 determinant. AN - 70644185; 11225991 AB - p53 mutations are frequently found in human cancers and are often associated with the overexpression of wild-type (WT) protein or peptide sequences, supporting the notion that WT p53 epitopes may serve as potential targets for tumor immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor-associated antigen (TAA) model, based on immune recognition of a WT p53 determinant. WT p53-peptide-specific, major histocompatibility complex (MHC) classI-restricted CTL were produced from immunocompetent C57BL/6 (H-2b) mice after immunization with a previously defined WT p53 peptide (p53(232-240)) Epitope-specific CTL were then employed to identify syngeneic tumor cell populations expressing that antigenic determinant. Two syngeneic tumor cell lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express the endogenous WT p53(232-240) determinant naturally, as defined by CD8 + CTL recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was due to immune recognition of the p53(232-240) peptide epitope. The p53(232-240)-specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53-specific CTL could distinguish between tumor cells expressing self-TAA and normal host cells. We have demonstrated, for the first time, that the adoptive transfer of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8- CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent mice, which display antitumor activity both in vitro and in vivo (by adoptive transfer), may have implications for the immunotherapy of certain p53-expressing malignancies. JF - Cancer immunology, immunotherapy : CII AU - Hilburger Ryan, M AU - Abrams, S I AD - Laboratory of Tumor Immunology and Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1402, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 603 EP - 612 VL - 49 IS - 11 SN - 0340-7004, 0340-7004 KW - Antigens, Neoplasm KW - 0 KW - Cytokines KW - Epitopes KW - Peptides KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Lymphocyte Activation KW - Animals KW - Tumor Cells, Cultured KW - Cytokines -- biosynthesis KW - Mice, Inbred C57BL KW - Peptides -- immunology KW - Cytotoxicity Tests, Immunologic KW - Mice KW - Epitopes -- immunology KW - Antigens, Neoplasm -- immunology KW - Immunization KW - Female KW - Epitopes -- metabolism KW - T-Lymphocytes, Cytotoxic -- transplantation KW - Lung Neoplasms -- secondary KW - Immunotherapy, Adoptive KW - Lung Neoplasms -- therapy KW - T-Lymphocytes, Cytotoxic -- immunology KW - Tumor Suppressor Protein p53 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70644185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.atitle=Characterization+of+CD8%2B+cytotoxic+T+lymphocyte%2Ftumor+cell+interactions+reflecting+recognition+of+an+endogenously+expressed+murine+wild-type+p53+determinant.&rft.au=Hilburger+Ryan%2C+M%3BAbrams%2C+S+I&rft.aulast=Hilburger+Ryan&rft.aufirst=M&rft.date=2001-01-01&rft.volume=49&rft.issue=11&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=03407004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-08 N1 - Date created - 2001-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single-nucleotide primer extension assay by capillary electrophoresis laser-induced fluorescence. AN - 70639899; 11242966 JF - Methods in molecular biology (Clifton, N.J.) AU - Piggee, C A AU - Karger, B L AD - Laboratory of Neurotoxicology, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 89 EP - 94 VL - 163 SN - 1064-3745, 1064-3745 KW - DNA Primers KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Humans KW - DNA -- genetics KW - DNA -- analysis KW - Lasers KW - Fluorescence KW - Point Mutation KW - Electrophoresis, Capillary -- methods KW - Electrophoresis, Capillary -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70639899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Single-nucleotide+primer+extension+assay+by+capillary+electrophoresis+laser-induced+fluorescence.&rft.au=Piggee%2C+C+A%3BKarger%2C+B+L&rft.aulast=Piggee&rft.aufirst=C&rft.date=2001-01-01&rft.volume=163&rft.issue=&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates. AN - 70632839; 11221960 AB - Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment derived from the plant Hypericum perforatum (St John's Wort). The compound has been synthesized and shown to inhibit the growth of malignant glioma cell lines in vitro via inhibition of protein kinase C. Oral hypericin has entered clinical trials in adults with recurrent malignant glioma. The present study was performed to characterize the plasma pharmacokinetics (PK) and cerebrospinal fluid (CSF) penetration of hypericin in nonhuman primates. Hypericin was administered as an intravenous bolus dose of 2 mg/kg (n = 3) or 5 mg/kg (n = 1). Plasma and CSF (ventricular or lumbar) were sampled prior to administration and at frequent intervals for up to 50 h after administration of the drug. Hypericin concentrations in plasma and CSF were determined using a specific reverse-phase HPLC assay. Mean peak plasma concentration of hypericin following the 2 mg/kg dose was 142 +/- 45 microM. Elimination of hypericin from plasma was biexponential, with an average alpha half-life of 2.8 +/- 0.3 h and average terminal half-life of 26 +/- 14 h. The 2 mg/kg dose in the nonhuman primate was sufficient to maintain plasma concentrations above 10 microM (the in vitro concentration required for growth inhibition of human glioma cell lines) for up to 12 h. No hypericin was detected in the CSF of any animal (lower limit of detection 0.1 microM); the CSF penetration is therefore less than 1%. A severe dose-limiting photosensitivity skin rash was seen at the 5 mg/kg dose level. JF - Cancer chemotherapy and pharmacology AU - Fox, E AU - Murphy, R F AU - McCully, C L AU - Adamson, P C AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 41 EP - 44 VL - 47 IS - 1 SN - 0344-5704, 0344-5704 KW - Antineoplastic Agents KW - 0 KW - Perylene KW - 5QD5427UN7 KW - hypericin KW - 7V2F1075HD KW - Index Medicus KW - Animals KW - Injections, Intravenous KW - Half-Life KW - Macaca mulatta KW - Time Factors KW - Drug Evaluation, Preclinical KW - Male KW - Chromatography, High Pressure Liquid KW - Perylene -- analogs & derivatives KW - Perylene -- blood KW - Antineoplastic Agents -- cerebrospinal fluid KW - Antineoplastic Agents -- blood KW - Perylene -- adverse effects KW - Perylene -- cerebrospinal fluid KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70632839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Plasma+pharmacokinetics+and+cerebrospinal+fluid+penetration+of+hypericin+in+nonhuman+primates.&rft.au=Fox%2C+E%3BMurphy%2C+R+F%3BMcCully%2C+C+L%3BAdamson%2C+P+C&rft.aulast=Fox&rft.aufirst=E&rft.date=2001-01-01&rft.volume=47&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of heterozygosity frequency at the Trp53 locus in p53-deficient (+/-) mouse tumors is carcinogen-and tissue-dependent. AN - 70630382; 11159747 AB - Mutagenic carcinogens rapidly induced tumors in the p53 haploinsufficient mouse. Heterozygous p53-deficient (+/-) mice were exposed to different mutagenic carcinogens to determine whether p53 loss of heterozygosity (LOH) was carcinogen-and tissue-dependent. For 26 weeks, C57BL/6 (N4) [corrected] p53-deficient (+/-) male or female mice were exposed to p-cresidine, benzene or phenolphthalein. Tumors were examined first for loss of the wild-type p53 allele. p-cresidine induced p53 LOH in three of 13 bladder tumors, whereas hepatocellular tumors showed p53 LOH in carcinomas (2/2), but not in adenomas (0/3). Benzene induced p53 LOH in 13 of 16 tumors examined. Finally, phenolphthalein induced p53 LOH in all tumors analyzed (21/21). Analysis of the p-cresidine-induced bladder tumors by cold single-strand conformation polymorphism (SSCP) analysis of exon 4-9 amplicons failed to demonstrate polymorphisms associated with mutations in tumors that retained the p53 wild-type allele. p-cresidine induced a dose-related increase in lacI mutations in bladder DNA. In summary, these data demonstrate that loss of the wild-type allele occurred frequently in thymic lymphomas and sarcomas, but less frequently in carcinomas of the urinary bladder. In the bladder carcinomas other mechanisms may be operational. These might include (i) other mechanisms of p53 inactivation, (ii) inactivating mutations occurring outside exons 4-9 or (iii) p53 haploinsufficiency creating a condition that favors other critical genetic events which drive bladder carcinogenesis, as evidenced by the significant decrease in tumor latency. Understanding the mechanisms of p53 LOH and chemical carcinogenesis in this genetically altered model could lead to better models for prospective identification and understanding of potential human carcinogens and the role of the p53 tumor suppressor gene in different pathways of chemical carcinogenesis. JF - Carcinogenesis AU - French, J E AU - Lacks, G D AU - Trempus, C AU - Dunnick, J K AU - Foley, J AU - Mahler, J AU - Tice, R R AU - Tennant, R W AD - Laboratory of Environmental Mutagenesis and Carcinogenesis, Research Triangle Park, NC 27709, USA. french@niehs.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 99 EP - 106 VL - 22 IS - 1 SN - 0143-3334, 0143-3334 KW - Aniline Compounds KW - 0 KW - Bacterial Proteins KW - Carcinogens KW - Escherichia coli Proteins KW - Lac Repressors KW - Repressor Proteins KW - Tumor Suppressor Protein p53 KW - cresidine KW - 4C11L78UR3 KW - Phenolphthalein KW - 6QK969R2IF KW - Benzene KW - J64922108F KW - Index Medicus KW - Mutagenesis -- drug effects KW - Animals KW - Bacterial Proteins -- genetics KW - Urinary Bladder Neoplasms -- pathology KW - Sarcoma, Experimental -- chemically induced KW - Urinary Bladder Neoplasms -- genetics KW - Benzene -- toxicity KW - Lymphoma -- chemically induced KW - Sarcoma, Experimental -- pathology KW - Mice KW - Aniline Compounds -- toxicity KW - Sarcoma, Experimental -- genetics KW - Repressor Proteins -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Alleles KW - Lymphoma -- genetics KW - Mice, Inbred C57BL KW - Phenolphthalein -- toxicity KW - Lymphoma -- pathology KW - Female KW - Male KW - Urinary Bladder Neoplasms -- chemically induced KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Genes, p53 -- drug effects KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Genes, p53 -- genetics KW - Carcinogens -- toxicity KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms, Experimental -- pathology KW - Loss of Heterozygosity -- drug effects KW - Tumor Suppressor Protein p53 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70630382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Loss+of+heterozygosity+frequency+at+the+Trp53+locus+in+p53-deficient+%28%2B%2F-%29+mouse+tumors+is+carcinogen-and+tissue-dependent.&rft.au=French%2C+J+E%3BLacks%2C+G+D%3BTrempus%2C+C%3BDunnick%2C+J+K%3BFoley%2C+J%3BMahler%2C+J%3BTice%2C+R+R%3BTennant%2C+R+W&rft.aulast=French&rft.aufirst=J&rft.date=2001-01-01&rft.volume=22&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Carcinogenesis 2002 Feb;23(2):373 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosome 11 allelotypes reflect a mechanism of chemical carcinogenesis in heterozygous p53-deficient mice. AN - 70617072; 11159746 AB - Mice heterozygous for a null p53 allele were administered three well-characterized carcinogens to learn more about mechanisms of carcinogenesis and to evaluate the p53-deficient mouse as a tool for identifying potential human carcinogens. Benzene-induced sarcomas, p-cresidine-induced bladder carcinomas and phenolphthalein-induced thymic lymphomas were allelotyped at the Trp53 locus and chromosome 11 simple sequence length polymorphic (SSLP) loci. Loss of Trp53 and loss of one copy of chromosome 11 occurred in each of 10 lymphomas examined and each of the eight sarcomas examined. Loss of Trp53 and loss of heterozygosity (LOH) at SSLP loci were sporadic in the bladder carcinomas. However, LOH was detected at two or more SSLP loci in six of the eight bladder tumors examined. Loss of one complete copy of chromosome 11 was implicated in three of the bladder tumors where LOH occurred at seven or more widely dispersed SSLP loci. Loss of one copy of chromosome 11 likely occurred through a p53-mediated selection process since Trp53 is located on mouse chromosome 11 and only one copy harbored a functional gene. The data suggest that loss occurred through a mechanism common among the three tumor types. Allelotype patterns of the maternal chromosome 11 were inconsistent with those expected from a nullizygous C57BL/6-Trp53 (N4) x inbred C57BL/6 cross which was reported for production of the mice under investigation. However, comparison with individual control tissues still allowed deduction of maternal chromosome loss. If the breeding protocols were carried out as described, the unexpected allelotype patterns observed in histologically normal tissues might be due to mitotic homologous recombination during embryogenesis. JF - Carcinogenesis AU - Hulla, J E AU - French, J E AU - Dunnick, J K AD - University of North Dakota School of Medicine, Grand Forks, ND, USA. hulla@niehs.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 89 EP - 98 VL - 22 IS - 1 SN - 0143-3334, 0143-3334 KW - Aniline Compounds KW - 0 KW - Carcinogens KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - cresidine KW - 4C11L78UR3 KW - Phenolphthalein KW - 6QK969R2IF KW - Benzene KW - J64922108F KW - Index Medicus KW - Animals KW - Sarcoma, Experimental -- chemically induced KW - Polymorphism, Genetic KW - Urinary Bladder Neoplasms -- genetics KW - Benzene -- toxicity KW - Thymus Neoplasms -- chemically induced KW - Lymphoma -- chemically induced KW - Mice KW - Aniline Compounds -- toxicity KW - Sarcoma, Experimental -- genetics KW - DNA, Neoplasm -- isolation & purification KW - Chromosomes -- genetics KW - Alleles KW - Loss of Heterozygosity KW - Lymphoma -- genetics KW - Heterozygote KW - Thymus Neoplasms -- genetics KW - Mice, Inbred C57BL KW - Carcinogenicity Tests KW - Crosses, Genetic KW - DNA, Neoplasm -- genetics KW - Phenolphthalein -- toxicity KW - Male KW - Female KW - Urinary Bladder Neoplasms -- chemically induced KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Genes, p53 -- genetics KW - Carcinogens -- toxicity KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70617072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Chromosome+11+allelotypes+reflect+a+mechanism+of+chemical+carcinogenesis+in+heterozygous+p53-deficient+mice.&rft.au=Hulla%2C+J+E%3BFrench%2C+J+E%3BDunnick%2C+J+K&rft.aulast=Hulla&rft.aufirst=J&rft.date=2001-01-01&rft.volume=22&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Carcinogenesis. 2001 Nov;22(11):1891 [11698354] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia. AN - 70613173; 11163778 AB - The specific intracellular effects of antipsychotic drugs are largely unknown. Studies in animals have suggested that antipsychotics modify the expression of various intraneuronal proteins, but no analogous in vivo data in humans are available. The objective of the present study was to assess whether antipsychotics modify N-acetylaspartate (an intraneuronal marker of neuronal functional integrity) measures in brains of patients with schizophrenia. We used proton magnetic resonance spectroscopic imaging to study 23 patients with schizophrenia (DSM-IV diagnosis) using a within-subject design. Patients were studied twice: once while on a stable regimen of antipsychotic drug treatment (for at least 4 weeks) and once while off medication for at least 2 weeks. Several cortical and subcortical regions were assessed, including the dorsolateral prefrontal cortex and the hippocampal area. Analysis of variance showed that, while on antipsychotics, patients had significantly higher N-acetylaspartate measures in the dorsolateral prefrontal cortex (p =.002). No other region showed any significant effect of treatment. These results indicate that antipsychotic drugs increase N-acetylaspartate measures selectively in the dorsolateral prefrontal cortices of patients with schizophrenia, suggesting that these drugs modify in a regionally specific manner the function of a population of cortical neurons. N-Acetylaspartate measures may provide a useful tool to further investigate the effects of antipsychotics at the intracellular level. JF - Biological psychiatry AU - Bertolino, A AU - Callicott, J H AU - Mattay, V S AU - Weidenhammer, K M AU - Rakow, R AU - Egan, M F AU - Weinberger, D R AD - Clinical Brain Disorders Branch, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Room 4S235 (MSC 1379), Bethesda, MD 20892, USA. Y1 - 2001/01/01/ PY - 2001 DA - 2001 Jan 01 SP - 39 EP - 46 VL - 49 IS - 1 SN - 0006-3223, 0006-3223 KW - Antipsychotic Agents KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - N-acetylaspartate KW - 997-55-7 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Psychiatric Status Rating Scales KW - Humans KW - Brain -- pathology KW - Adult KW - Male KW - Female KW - Magnetic Resonance Spectroscopy KW - Aspartic Acid -- metabolism KW - Aspartic Acid -- analogs & derivatives KW - Schizophrenia -- metabolism KW - Brain Chemistry -- drug effects KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia -- drug therapy KW - Schizophrenia -- pathology KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70613173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=The+effect+of+treatment+with+antipsychotic+drugs+on+brain+N-acetylaspartate+measures+in+patients+with+schizophrenia.&rft.au=Bertolino%2C+A%3BCallicott%2C+J+H%3BMattay%2C+V+S%3BWeidenhammer%2C+K+M%3BRakow%2C+R%3BEgan%2C+M+F%3BWeinberger%2C+D+R&rft.aulast=Bertolino&rft.aufirst=A&rft.date=2001-01-01&rft.volume=49&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats. AN - 70604481; 11215676 AB - We investigated the effects of altered endogenous nighttime melatonin concentrations on mammary tumor production in an N-nitroso-N-methylurea (NMU)-induced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting in a decrease in nighttime serum melatonin concentrations, 2) to evaluate whether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppressed serum melatonin concentrations on the incidence and progression of NMU-induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-induced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light: dark cycle decreased the magnitude of the nocturnal rise of serum melatonin concentrations in rats by approximately 65%. After 2 weeks of nightly intermittent light exposures, an average decrease of the peak nighttime serum melatonin concentrations of approximately 35% occurred. The amelioration continued and, at 10 weeks, peak nighttime serum melatonin concentrations were still decreased, by approximately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multiplicity, and weight of NMU-induced mammary tumors were assessed. A group of pinealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were moderately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 NMU controls, 28/40 NMU + light, 31/40 NMU + Px), multiplicity (2.18 tumors/tumor-bearing NMU control, 1.89 NMU + light, 2.39 NMU + Px), or average tumor weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Px). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, animals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additionally, rats that had been pinealectomized at 4 weeks of age had serum melatonin concentrations that were markedly higher than the expected baseline concentrations for pinealectomized rats (<15 pg/ml), suggesting the reestablishment of a melatonin cycle. This finding was unexpected and suggests that melatonin can be produced by an organ or tissue other than the pineal gland. JF - Toxicologic pathology AU - Travlos, G S AU - Wilson, R E AU - Murrell, J A AU - Chignell, C F AU - Boorman, G A AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. travlos@niehs.nih.gov PY - 2001 SP - 126 EP - 136 VL - 29 IS - 1 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Methylnitrosourea KW - 684-93-5 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Light KW - Pineal Gland -- physiology KW - Female KW - Organ Size -- drug effects KW - Melatonin -- blood KW - Mammary Neoplasms, Experimental -- chemically induced KW - Circadian Rhythm -- physiology KW - Methylnitrosourea -- toxicity KW - Carcinogens -- toxicity KW - Melatonin -- metabolism KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70604481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+effect+of+short+intermittent+light+exposures+on+the+melatonin+circadian+rhythm+and+NMU-induced+breast+cancer+in+female+F344%2FN+rats.&rft.au=Travlos%2C+G+S%3BWilson%2C+R+E%3BMurrell%2C+J+A%3BChignell%2C+C+F%3BBoorman%2C+G+A&rft.aulast=Travlos&rft.aufirst=G&rft.date=2001-01-01&rft.volume=29&rft.issue=1&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reproductive endocrinology and toxicological pathology over the life span of the female rodent. AN - 70600159; 11215687 AB - Understanding the pathology of the female reproductive system with respect to toxicology requires a basic understanding of morphology and function of the system over time because the nature of the female reproductive system is cyclical. Thus, the morphology and the endocrinology is dependent on age and time, as form follows function and function follows form. The life span of the rodent is used as an outline to present an overview of key morphological and endocrinological events important for toxicologic pathologists to consider in study evaluations. Environmental and pharmaceutical compounds differentially impact the organs individually and/or the system in its entirety in a time- and dose-dependent way. Examples are used to illustrate the consequences of exposures at different times and with different outcomes. JF - Toxicologic pathology AU - Davis, B J AU - Travlos, G AU - McShane, T AD - Laboratory of Women's Health, NIEHS, Research Triangle Park, North Carolina 27709, USA. Davis1@niehs.nih.gov PY - 2001 SP - 77 EP - 83 VL - 29 IS - 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Estrus -- drug effects KW - Female KW - Infertility, Female -- pathology KW - Rodentia -- physiology KW - Reproduction -- physiology KW - Endocrine Glands -- drug effects KW - Endocrine Glands -- pathology KW - Endocrine Glands -- physiology KW - Infertility, Female -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70600159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Reproductive+endocrinology+and+toxicological+pathology+over+the+life+span+of+the+female+rodent.&rft.au=Davis%2C+B+J%3BTravlos%2C+G%3BMcShane%2C+T&rft.aulast=Davis&rft.aufirst=B&rft.date=2001-01-01&rft.volume=29&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer prevention studies in p53-deficient mice. AN - 70599403; 11215677 AB - Future progress in mechanism-based cancer prevention research may be facilitated by animal models displaying specific genetic susceptibilities for cancer, such as mice deficient in 1 (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. We observed in p53-/- mice that calorie restriction (CR) increased the latency of spontaneous tumor development (mostly lymphomas) by approximately 75%, decreased serum insulin-like growth factor-1 (IGF-1) and leptin levels, slowed thymocyte cell cycle traverse, and induced apoptosis in immature thymocytes. In p53+/- mice, CR and a 1 d/wk fast each delayed spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreased serum IGF-1 and leptin levels, even when begun late in life. In p53+/-Wnt-1 transgenic mice, a mammary tumor model, the same interventions increased mammary tumor latency and reduced mean serum IGF-1 and leptin levels to <50% of those of control mice. We capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches. These examples clearly indicate that mice with specific (and humanlike) genetic susceptibilities for cancer are powerful models for testing interventions that may inhibit carcinogenesis in humans. JF - Toxicologic pathology AU - Hursting, S D AU - Perkins, S N AU - Donehower, L A AU - Davis, B J AD - Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. PY - 2001 SP - 137 EP - 141 VL - 29 IS - 1 SN - 0192-6233, 0192-6233 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Mice KW - Mice, Transgenic KW - Female KW - Pregnancy KW - Neoplasms -- prevention & control KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70599403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Cancer+prevention+studies+in+p53-deficient+mice.&rft.au=Hursting%2C+S+D%3BPerkins%2C+S+N%3BDonehower%2C+L+A%3BDavis%2C+B+J&rft.aulast=Hursting&rft.aufirst=S&rft.date=2001-01-01&rft.volume=29&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. AN - 70599235; 11205902 AB - We sought to characterize the interactions of flavopiridol with members of the ATP-binding cassette (ABC) transporter family. Cells overexpressing multidrug resistance-1 (MDR-1) and multidrug resistance-associated protein (MRP) did not exhibit appreciable flavopiridol resistance, whereas cell lines overexpressing the ABC half-transporter, ABCG2 (MXR/BCRP/ABCP1), were found to be resistant to flavopiridol. Flavopiridol at a concentration of 10 microM was able to prevent MRP-mediated calcein efflux, whereas Pgp-mediated transport of rhodamine 123 was unaffected at flavopiridol concentrations of up to 100 microM. To determine putative mechanisms of resistance to flavopiridol, we exposed the human breast cancer cell line MCF-7 to incrementally increasing concentrations of flavopiridol. The resulting resistant subline, MCF-7 FLV1000, is maintained in 1,000 nM flavopiridol and was found to be 24-fold resistant to flavopiridol, as well as highly cross-resistant to mitoxantrone (675-fold), topotecan (423-fold), and SN-38 (950-fold), the active metabolite of irinotecan. Because this cross-resistance pattern is consistent with that reported for ABCG2-overexpressing cells, cytotoxicity studies were repeated in the presence of 5 microM of the ABCG2 inhibitor fumitremorgin C (FTC), and sensitivity of MCF-7 FLV1000 cells to flavopiridol, mitoxantrone, SN-38, and topotecan was restored. Mitoxantrone efflux studies were performed, and high levels of FTC-reversible mitoxantrone efflux were found. Northern blot and PCR analysis revealed overexpression of the ABCG2 gene. Western blot confirmed overexpression of ABCG2; neither P-glycoprotein nor MRP overexpression was detected. These results suggest that ABCG2 plays a role in resistance to flavopiridol. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Robey, R W AU - Medina-Pérez, W Y AU - Nishiyama, K AU - Lahusen, T AU - Miyake, K AU - Litman, T AU - Senderowicz, A M AU - Ross, D D AU - Bates, S E AD - Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 145 EP - 152 VL - 7 IS - 1 SN - 1078-0432, 1078-0432 KW - ABCG2 protein, human KW - 0 KW - ATP Binding Cassette Transporter, Sub-Family G, Member 2 KW - Antineoplastic Agents KW - DNA Primers KW - Flavonoids KW - Indoles KW - Mycotoxins KW - Neoplasm Proteins KW - P-Glycoproteins KW - Piperidines KW - Radiopharmaceuticals KW - alvocidib KW - 45AD6X575G KW - Mitoxantrone KW - BZ114NVM5P KW - tryptoquivaline KW - CW5S8OP3VO KW - Index Medicus KW - Blotting, Northern KW - Mycotoxins -- pharmacology KW - Radiopharmaceuticals -- metabolism KW - Humans KW - Cell Division -- drug effects KW - Mitoxantrone -- pharmacology KW - Drug Resistance, Neoplasm KW - P-Glycoproteins -- metabolism KW - Polymerase Chain Reaction KW - Blotting, Western KW - Indoles -- pharmacology KW - P-Glycoproteins -- antagonists & inhibitors KW - Fluorescent Antibody Technique KW - DNA Primers -- chemistry KW - Breast Neoplasms -- drug therapy KW - Neoplasm Proteins -- biosynthesis KW - Tumor Cells, Cultured -- metabolism KW - Neoplasm Proteins -- antagonists & inhibitors KW - Tumor Cells, Cultured -- drug effects KW - Antineoplastic Agents -- metabolism KW - Breast Neoplasms -- metabolism KW - Piperidines -- pharmacology KW - Breast Neoplasms -- pathology KW - ATP-Binding Cassette Transporters -- biosynthesis KW - Tumor Cells, Cultured -- pathology KW - Flavonoids -- pharmacology KW - ATP-Binding Cassette Transporters -- antagonists & inhibitors KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70599235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Overexpression+of+the+ATP-binding+cassette+half-transporter%2C+ABCG2+%28Mxr%2FBCrp%2FABCP1%29%2C+in+flavopiridol-resistant+human+breast+cancer+cells.&rft.au=Robey%2C+R+W%3BMedina-P%C3%A9rez%2C+W+Y%3BNishiyama%2C+K%3BLahusen%2C+T%3BMiyake%2C+K%3BLitman%2C+T%3BSenderowicz%2C+A+M%3BRoss%2C+D+D%3BBates%2C+S+E&rft.aulast=Robey&rft.aufirst=R&rft.date=2001-01-01&rft.volume=7&rft.issue=1&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary tumor induction and premature ovarian failure in ApcMin mice are not enhanced by Brca2 deficiency. AN - 70597967; 11215675 AB - Inherited BRCA2 mutations predispose individuals to breast cancer and increase risk at other sites. Recent studies have suggested a role for the APC I1307K allele as a low-penetrance breast cancer susceptibility gene that enhances the phenotypic effects of BRCA1 and BRCA2 mutations. To model the consequences of inheriting mutant alleles of the BRCA2 and APC tumor suppressor genes, we examined tumor outcome in C57BL/6 mice with mutations in the Brca2 and Apc genes. We hypothesized that if the Brca2 and Apc genes were interacting to influence mammary tumor susceptibility, then mammary tumor incidence and/or multiplicity would be altered in mice that had inherited mutations in both genes. Female and male offspring treated with a single IP injection of 50 mg/kg N-ethyl-N-nitrosourea (ENU) at 35 days of age developed mammary adenoacanthomas by 100 days of age. The female Apc-mutant and Brca2/Apc double-mutant progeny had mean mammary tumor multiplicities of 6.7+/-2.8 and 7.2+/-2.7, respectively, compared to wild-type and Brca2-mutant females, which had mean mammary tumor multiplicities of 0.1+/-0.4 and 0.3+/-0.5, respectively. Female ENU-treated Apc-mutant and Brca2/Apc double heterozygotes were also susceptible to premature ovarian failure. Thus, the inheritance of an Apc mutation predisposes ENU-treated female and male mice to mammary tumors and, in the case of female mice, to ovarian failure. These results indicate that mammary tumor development in Apc-mutant mice can progress independently of ovarian hormones. The Apc mutation-driven phenotypes were not modified by mutation of Brca2, perhaps because Brca2 acts in a hormonally dependent pathway of mammary carcinogenesis. JF - Toxicologic pathology AU - Bennett, L M AU - McAllister, K A AU - Ward, T AU - Malphurs, J AU - Collins, N K AU - Seely, J C AU - Davis, B J AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. bennett42@llnl.gov PY - 2001 SP - 117 EP - 125 VL - 29 IS - 1 SN - 0192-6233, 0192-6233 KW - BRCA2 Protein KW - 0 KW - Carcinogens KW - Neoplasm Proteins KW - Transcription Factors KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Ethylnitrosourea -- toxicity KW - Heterozygote KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Carcinogens -- toxicity KW - Mice KW - Male KW - Female KW - Mice, Knockout KW - Ovarian Diseases -- genetics KW - Adenocarcinoma -- chemically induced KW - Mammary Neoplasms, Experimental -- genetics KW - Neoplasm Proteins -- deficiency KW - Ovarian Diseases -- chemically induced KW - Adenocarcinoma -- genetics KW - Metaplasia -- chemically induced KW - Metaplasia -- genetics KW - Transcription Factors -- genetics KW - Genes, APC -- genetics KW - Adenocarcinoma -- pathology KW - Mammary Neoplasms, Experimental -- pathology KW - Mammary Neoplasms, Experimental -- chemically induced KW - Ovarian Diseases -- pathology KW - Neoplasm Proteins -- genetics KW - Metaplasia -- pathology KW - Transcription Factors -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70597967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Mammary+tumor+induction+and+premature+ovarian+failure+in+ApcMin+mice+are+not+enhanced+by+Brca2+deficiency.&rft.au=Bennett%2C+L+M%3BMcAllister%2C+K+A%3BWard%2C+T%3BMalphurs%2C+J%3BCollins%2C+N+K%3BSeely%2C+J+C%3BDavis%2C+B+J%3BWiseman%2C+R+W&rft.aulast=Bennett&rft.aufirst=L&rft.date=2001-01-01&rft.volume=29&rft.issue=1&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polo-like kinase interacts with proteasomes and regulates their activity. AN - 70597806; 11205743 AB - The polo-like kinase (Plk) has been shown to be associated with the anaphase-promoting complex at the transition from metaphase to anaphase and to regulate ubiquitination, the process that targets proteins for degradation by proteasomes. In this study, we have identified proteasomal proteins interacting with Plk by mass spectrometry and found that Plk and 20S proteasome subunits could be reversibly immunoprecipitated from both human CA46 cells and HEK 293 cells transfected with HA-Plk. Furthermore, both coprecipitated Plk and baculovirus-expressed Plk were able to phosphorylate proteasome subunits, and metabolic labeling studies indicate that Plk is partially responsible for the phosphorylation of 20S proteasome subunits C9 and C8 in vivo. In addition, phosphorylation of proteasomes by Plk enhanced proteolytic activity toward an artificial substrate Suc-L-L-V-Y-AMC in vitro and in vivo. Finally, we were also able to detect Plk associated with 26S proteasomes under certain conditions. Together our results suggest that Plk is an important mitotic regulator of proteasome activity. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Feng, Y AU - Longo, D L AU - Ferris, D K AD - Biological Mechanisms Section, Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 29 EP - 37 VL - 12 IS - 1 SN - 1044-9523, 1044-9523 KW - Drosophila Proteins KW - 0 KW - Immunoglobulin G KW - Multienzyme Complexes KW - Recombinant Proteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Animals KW - Mass Spectrometry KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Anaphase KW - Baculoviridae -- metabolism KW - Precipitin Tests KW - Metaphase KW - Insects KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Mitosis KW - Electrophoresis, Gel, Two-Dimensional KW - Okadaic Acid -- pharmacology KW - Immunoglobulin G -- metabolism KW - Cell Line KW - Multienzyme Complexes -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cysteine Endopeptidases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70597806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Polo-like+kinase+interacts+with+proteasomes+and+regulates+their+activity.&rft.au=Feng%2C+Y%3BLongo%2C+D+L%3BFerris%2C+D+K&rft.aulast=Feng&rft.aufirst=Y&rft.date=2001-01-01&rft.volume=12&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of induction of transforming growth factor-beta type II receptor gene expression by v-Src in murine myeloid cells. AN - 70597788; 11205746 AB - Transforming growth factor (TGF)-beta1 plays an important role during hematopoiesis. Previously, we had shown that the growth of a v-Src-transformed myeloid cell line was markedly more inhibited by TGF-beta treatment when compared with the wild-type myeloid cell line. To investigate the increased growth sensitivity of the v-Src-transformed myeloid cell line, 32D-src, to TGF-beta, we examined expression of the TGF-beta type II receptor (TGF-beta RII) gene in myeloid cell lines. Northem blot analysis showed that expression of approximately 8- and 6-kb species of TGF-beta RII transcripts was markedly increased in the 32D-src cell line. The expression of the TGF-beta RII promoter linked to a reporter gene was increased 23-fold by v-Src. DNA transfection and electrophoretic mobility shift assay revealed that v-Src induces TGF-beta RII promoter activity through an AP1/ATF2-like sequence (-219 to -172), ETS binding sites (+1 to +36), and the inverted CCAAT box (-81 to -77). Novel DNA-protein complexes with ETS binding sites are significantly increased in v-src-transformed cell lines compared with the control cell line. These results suggest that v-Src induces activity of the TGF-beta RII promoter through multiple elements by inducing expression of nuclear proteins interacting with these elements. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Park, S H AU - Birchenall-Roberts, M C AU - Yi, Y AU - Lee, B I AU - Lee, D K AU - Bertolette, D C AU - Fu, T AU - Ruscetti, F AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 9 EP - 18 VL - 12 IS - 1 SN - 1044-9523, 1044-9523 KW - Cross-Linking Reagents KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Luciferases KW - EC 1.13.12.- KW - Oncogene Protein pp60(v-src) KW - EC 2.7.10.2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Plasmids -- metabolism KW - Blotting, Northern KW - Cell Nucleus -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Luciferases -- metabolism KW - Mice KW - Protein Binding KW - Transcriptional Activation KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Base Sequence KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Transfection KW - Models, Genetic KW - Binding, Competitive KW - Molecular Sequence Data KW - Genes, Reporter KW - Response Elements KW - Cell Line KW - Myeloid Cells -- metabolism KW - Oncogene Protein pp60(v-src) -- metabolism KW - Gene Expression Regulation KW - Receptors, Transforming Growth Factor beta -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70597788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Mechanism+of+induction+of+transforming+growth+factor-beta+type+II+receptor+gene+expression+by+v-Src+in+murine+myeloid+cells.&rft.au=Park%2C+S+H%3BBirchenall-Roberts%2C+M+C%3BYi%2C+Y%3BLee%2C+B+I%3BLee%2C+D+K%3BBertolette%2C+D+C%3BFu%2C+T%3BRuscetti%2C+F%3BKim%2C+S+J&rft.aulast=Park&rft.aufirst=S&rft.date=2001-01-01&rft.volume=12&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantification of immunotoxin number for complete therapeutic response. AN - 70596723; 11217362 JF - Methods in molecular biology (Clifton, N.J.) AU - Kreitman, R J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 111 EP - 123 VL - 166 SN - 1064-3745, 1064-3745 KW - Antibodies, Monoclonal KW - 0 KW - B3(Fv)-PE38KDEL recombinant immunotoxin KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Recombinant Fusion Proteins -- analysis KW - Animals KW - Drug Screening Assays, Antitumor KW - Dose-Response Relationship, Drug KW - Humans KW - Leukemia, Experimental -- drug therapy KW - Mice KW - Mice, Nude KW - Tissue Distribution KW - Protein Binding KW - Receptors, Interleukin-2 -- immunology KW - Neoplastic Stem Cells -- drug effects KW - Neoplasm Transplantation KW - Leukemia -- drug therapy KW - Transfection KW - Clinical Trials, Phase I as Topic KW - Injections, Subcutaneous KW - Xenograft Model Antitumor Assays KW - Recombinant Fusion Proteins -- pharmacology KW - Lymphoma -- drug therapy KW - Mice, SCID KW - Recombinant Fusion Proteins -- therapeutic use KW - Remission Induction KW - Neoplasms -- drug therapy KW - Exotoxins -- pharmacology KW - Exotoxins -- analysis KW - Exotoxins -- administration & dosage KW - Immunotoxins -- analysis KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage KW - Immunotoxins -- pharmacology KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70596723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Quantification+of+immunotoxin+number+for+complete+therapeutic+response.&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2001-01-01&rft.volume=166&rft.issue=&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ecteinascidin 743 induces protein-linked DNA breaks in human colon carcinoma HCT116 cells and is cytotoxic independently of topoisomerase I expression. AN - 70596414; 11205907 AB - Ecteinascidin 743 (Et743; NSC 648766) is a potent antitumor agent presently in clinical trials. Et743 selectively alkylates guanine N2 from the minor groove of duplex DNA and bends the DNA toward the major groove. This differentiates Et743 from other DNA-alkylating agents presently in the clinic. To date, the cellular effects of Et743 have not been elucidated. Recently, Et743 DNA adducts have been found to suppress gene expression selectively and to induce topoisomerase I (top1) cleavage complexes in vitro and top1-DNA complexes in cell culture. In the present study, we characterized the DNA damage and the cell cycle response induced by Et743 in human colon carcinoma HCT116 cells. Alkaline elution experiments demonstrated that micromolar concentrations of Et743 produced comparable frequencies of DNA-protein cross-links and DNA single-strand breaks. The single-strand breaks were protein-cross-linked and were not associated with detectable DNA double-strand breaks. By contrast with camptothecin, these lesions persisted for several hours after drug removal and were not formed at 4 degrees C. Et743 treatment induced transient p53 elevation, dose-dependent cell cycle accumulation in G2-M and in G1- and S-phase, and inhibition of DNA synthesis. The sensitivity of camptothecin-resistant mouse leukemia P388/ CPT45 cells, which fail to express detectable top1, was similar to the sensitivity of wild-type P388 cells, suggesting that top1 is not a critical target for the antiproliferative activity of Et743. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Takebayashi, Y AU - Goldwasser, F AU - Urasaki, Y AU - Kohlhagen, G AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 185 EP - 191 VL - 7 IS - 1 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Alkylating KW - 0 KW - DNA, Neoplasm KW - Dioxoles KW - Formazans KW - Isoquinolines KW - Proliferating Cell Nuclear Antigen KW - Tetrahydroisoquinolines KW - Tetrazolium Salts KW - Tumor Suppressor Protein p53 KW - MTT formazan KW - 23305-68-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - trabectedin KW - ID0YZQ2TCP KW - Index Medicus KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Flow Cytometry KW - Tumor Suppressor Protein p53 -- metabolism KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Immunoenzyme Techniques KW - Cell Cycle -- drug effects KW - DNA, Neoplasm -- drug effects KW - Isoquinolines -- pharmacology KW - Colonic Neoplasms -- genetics KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Cell Division -- drug effects KW - Dioxoles -- pharmacology KW - DNA Topoisomerases, Type I -- metabolism KW - DNA Damage -- drug effects KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70596414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Ecteinascidin+743+induces+protein-linked+DNA+breaks+in+human+colon+carcinoma+HCT116+cells+and+is+cytotoxic+independently+of+topoisomerase+I+expression.&rft.au=Takebayashi%2C+Y%3BGoldwasser%2C+F%3BUrasaki%2C+Y%3BKohlhagen%2C+G%3BPommier%2C+Y&rft.aulast=Takebayashi&rft.aufirst=Y&rft.date=2001-01-01&rft.volume=7&rft.issue=1&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21. AN - 70594517; 11219490 AB - Mammary carcinomas that develop in C3 (1)/SV40 T- antigen (TAg) transgenic mice have lost the p53-mediated induction of p21, leading to increased cellular proliferation and significant elevations of cyclins and Cdks. To test whether p21 could serve as a target for anticancer therapy for this mammary cancer model, a retroviral delivery system for the inducible expression of p21 was developed. We demonstrate that overexpression of p21 in C3(1)/TAg mammary tumor cells using the retroviral inducible p21 expression system results in increased apoptosis, reduced cell proliferation in vitro and reduced tumor growth in vivo associated with reduced expression of cyclins D1 and E, and Cdks 2, 4, and 6. Reciprocal changes in the expression of p21 and p27(Kip1), another cell-cycle regulator, were also observed. Because reduced p21 expression occurs frequently in human breast cancer, restoration of the Cdk inhibitor p21 by gene therapy approaches may provide a method for inhibiting mammary tumor progression. JF - Cancer gene therapy AU - Shibata, M A AU - Yoshidome, K AU - Shibata, E AU - Jorcyk, C L AU - Green, J E AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 23 EP - 35 VL - 8 IS - 1 SN - 0929-1903, 0929-1903 KW - Cdkn1a protein, mouse KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA KW - 9007-49-2 KW - Tetracycline KW - F8VB5M810T KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - DNA -- metabolism KW - Mice, Nude KW - Mice KW - Mice, Transgenic KW - In Situ Nick-End Labeling KW - Blotting, Western KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Carcinogenicity Tests KW - Mice, Inbred C57BL KW - Tetracycline -- pharmacology KW - Retroviridae -- genetics KW - Female KW - Cell Division KW - Cyclins -- biosynthesis KW - Genetic Therapy -- methods KW - Cyclins -- metabolism KW - Mammary Neoplasms, Experimental -- prevention & control KW - Mammary Neoplasms, Experimental -- metabolism KW - Cyclins -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70594517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+gene+therapy&rft.atitle=Suppression+of+mammary+carcinoma+growth+in+vitro+and+in+vivo+by+inducible+expression+of+the+Cdk+inhibitor+p21.&rft.au=Shibata%2C+M+A%3BYoshidome%2C+K%3BShibata%2C+E%3BJorcyk%2C+C+L%3BGreen%2C+J+E&rft.aulast=Shibata&rft.aufirst=M&rft.date=2001-01-01&rft.volume=8&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Cancer+gene+therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhalation toxicity studies of the alpha,beta-unsaturated ketones: 2-cyclohexene-1-one. AN - 70592140; 11153058 AB - 2-Cyclohexene-1-one (CHX) is a cyclic alpha,beta-unsaturated ketone with broad human exposure. CHX is an environmental pollutant and is present in tobacco smoke and in soft drinks sweetened with cyclamate. Interest in the toxicity of this class of compounds is due to their structural similarity to the cytotoxin acrolein. In a pilot study, rats and mice were exposed to 0, 20, 40, or 80 ppm CHX for 6 h/day. The study was terminated after 4 days due to acute toxicity in the high-dose groups. In a subsequent 14-day study, mice and rats were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day. All animals survived exposure until terminal sacrifice. Body weights were not significantly different from controls after 14 days of exposure. Liver/body weights were increased in male and female mice exposed to 5 and 10 ppm, and in male and female rats exposed to 10 ppm CHX. Ninety-day toxicity studies were conducted to provide data required to design chronic toxicity and carcinogenicity studies of CHX if it is determined such studies are necessary. Groups of 10 male and female F-344 rats and B6C3F1 mice were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day for 13 wk. All animals survived until sacrifice. Body weights were not significantly different from controls after 13 wk of exposure. Liver weights were increased in male and female mice exposed to 5 and 10 ppm and in male and female rats exposed to 10 ppm CHX. No adverse effects on bone-marrow micronuclei, sperm motility, or vaginal cytology were observed. Microscopic lesions included hyperplasia, and squamous metaplasia in the nasal cavity in rats and mice of both sexes at all doses. Nasal-cavity erosion and suppurative inflammation also occurred in high-dose mice. Larynx and lung were not affected in either sex or species. Dose-related hepatic centrilobular cytoplasmic vacuolation was seen in male rats only. These data suggest that CHX acts as an alkylating agent primarily producing toxicity at the exposure site. JF - Inhalation toxicology AU - Cunningham, M L AU - Price, H C AU - O'Connor, R W AU - Moorman, M P AU - Mahler, J F AU - Nold, J B AU - Morgan, D L AD - Laboratory of Pharmacology and Chemistry, National Toxicology Program, Mail Drop B3-10, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. cunning1@niehs.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 25 EP - 36 VL - 13 IS - 1 SN - 0895-8378, 0895-8378 KW - Air Pollutants KW - 0 KW - Cyclohexanones KW - 2-cyclohexen-1-one KW - 445160R1U6 KW - Index Medicus KW - Vagina -- drug effects KW - Bone Marrow Cells -- drug effects KW - Animals KW - Liver -- pathology KW - Kidney -- pathology KW - Vagina -- pathology KW - Kidney -- drug effects KW - Nasal Cavity -- drug effects KW - Mice KW - Lung -- pathology KW - Sperm Motility -- drug effects KW - Rats KW - Nasal Cavity -- pathology KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Micronucleus Tests KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Bone Marrow Cells -- pathology KW - Toxicity Tests KW - Lung -- drug effects KW - Administration, Inhalation KW - Male KW - Female KW - Organ Size -- drug effects KW - Cyclohexanones -- toxicity KW - Cyclohexanones -- administration & dosage KW - Air Pollutants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70592140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inhalation+toxicology&rft.atitle=Inhalation+toxicity+studies+of+the+alpha%2Cbeta-unsaturated+ketones%3A+2-cyclohexene-1-one.&rft.au=Cunningham%2C+M+L%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BMoorman%2C+M+P%3BMahler%2C+J+F%3BNold%2C+J+B%3BMorgan%2C+D+L&rft.aulast=Cunningham&rft.aufirst=M&rft.date=2001-01-01&rft.volume=13&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Inhalation+toxicology&rft.issn=08958378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Device-dependent activity estimation and decay correction of radionuclide mixtures with application to Tc-94m PET studies. AN - 70590473; 11213920 AB - Multi-instrument activity estimation and decay correction techniques were developed for radionuclide mixtures, motivated by the desire for accurate quantitation of Tc-94m positron emission tomography (PET) studies. Tc-94m and byproduct Tc isotopes were produced by proton irradiation of enriched Mo-94 and natural Mo targets. Mixture activities at the end of bombardment were determined with a calibrated high purity germanium detector. The activity fractions of the greatest mixture impurities relative to 100% for Tc-94m averaged 10.0% (Tc-94g) and 3.3% (Tc-93) for enriched targets and 10.1% (Tc-94g), 11.0% (Tc-95), 255.8% (Tc-96m), and 7.2% (Tc-99m) for natural targets. These radioisotopes have different half-lives (e.g., 52.5 min for Tc-94m, 293 min for Tc-94g), positron branching ratios (e.g., 0.72 for Tc-94m, 0.11 for Tc-94g) and gamma ray emissions for themselves and their short-lived, excited Mo daughters. This complicates estimation of injected activity with a dose calibrator, in vivo activity with PET and blood sample activity with a gamma counter. Decay correction using only the Tc-94m half-life overestimates activity and is inadequate. For this reason analytic formulas for activity estimation and decay correction of radionuclide mixtures were developed. Isotope-dependent sensitivity factors for a PET scanner, dose calibrator, and gamma counter were determined using theoretical sensitivity models and fits of experimental decay curves to sums of exponentials with fixed decay rates. For up to 8 h after the end of bombardment with activity from enriched and natural Mo targets, decay-corrected activities were within 3% of the mean for three PET studies of a uniform cylinder, within 3% of the mean for six dose calibrator decay studies, and within 6% of the mean for four gamma counter decay studies. Activity estimation and decay correction for Tc-94m mixtures enable routine use of Tc-94m in quantitative PET, as illustrated by application to a canine Tc-94m sestamibi study. JF - Medical physics AU - Smith, M F AU - Daube-Witherspoon, M E AU - Plascjak, P S AU - Szajek, L P AU - Carson, R E AU - Everett, J R AU - Green, S L AU - Territo, P R AU - Balaban, R S AU - Bacharach, S L AU - Eckelman, W C AD - Nuclear Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. smith@nmdhst.cc.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 36 EP - 45 VL - 28 IS - 1 SN - 0094-2405, 0094-2405 KW - Radiopharmaceuticals KW - 0 KW - Technetium KW - 7440-26-8 KW - Technetium Tc 99m Sestamibi KW - 971Z4W1S09 KW - Index Medicus KW - Phantoms, Imaging KW - Radiation Dosage KW - Animals KW - Scattering, Radiation KW - Heart -- diagnostic imaging KW - Humans KW - Dogs KW - Biophysical Phenomena KW - Biophysics KW - Tomography, Emission-Computed -- statistics & numerical data KW - Tomography, Emission-Computed -- instrumentation KW - Tomography, Emission-Computed -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70590473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+physics&rft.atitle=Device-dependent+activity+estimation+and+decay+correction+of+radionuclide+mixtures+with+application+to+Tc-94m+PET+studies.&rft.au=Smith%2C+M+F%3BDaube-Witherspoon%2C+M+E%3BPlascjak%2C+P+S%3BSzajek%2C+L+P%3BCarson%2C+R+E%3BEverett%2C+J+R%3BGreen%2C+S+L%3BTerrito%2C+P+R%3BBalaban%2C+R+S%3BBacharach%2C+S+L%3BEckelman%2C+W+C&rft.aulast=Smith&rft.aufirst=M&rft.date=2001-01-01&rft.volume=28&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Medical+physics&rft.issn=00942405&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trial designs for cytostatic agents: are new approaches needed? AN - 70589207; 11134222 AB - Preclinical data suggest that some new anticancer agents directed at novel targets demonstrate tumor growth inhibition but not tumor shrinkage. Such cytostatic agents may offer clinical benefits for patients in the absence of tumor shrinkage. In addition, lower doses of some of these agents may be just as effective as higher doses, implying that toxicity may not be an ideal end point for dose finding. Because of these factors, the sequence and design of traditional phase I, II, and III trials used for cytotoxic agents (which typically shrink tumors and in a dose-dependent manner) may not be appropriate for cytostatic agents. This article discusses options for modifying trial designs to accommodate cytostatic agents. Examples are given where these options have been tried or are currently being tried. Recommendations given for choosing among the trial designs depend on what is known preclinically about the agents (eg, does one have a validated and reproducible biologic end point that can be used to guide a dose escalation?), what is known about the patient population being studied (eg, does one have a well-documented historical progression-free survival rate at 1 year for comparison with the experience of the new agent?), and the numbers of agents and patients available for participation in trials. Planned and ongoing trials will test the utility of some of these new approaches. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Korn, E L AU - Arbuck, S G AU - Pluda, J M AU - Simon, R AU - Kaplan, R S AU - Christian, M C AD - Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. korne@ctep.nci.nih.gov Y1 - 2001/01/01/ PY - 2001 DA - 2001 Jan 01 SP - 265 EP - 272 VL - 19 IS - 1 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Clinical Trials, Phase II as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - Sample Size KW - Drug Evaluation -- methods KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70589207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Clinical+trial+designs+for+cytostatic+agents%3A+are+new+approaches+needed%3F&rft.au=Korn%2C+E+L%3BArbuck%2C+S+G%3BPluda%2C+J+M%3BSimon%2C+R%3BKaplan%2C+R+S%3BChristian%2C+M+C&rft.aulast=Korn&rft.aufirst=E&rft.date=2001-01-01&rft.volume=19&rft.issue=1&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-25 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2001 Jun 15;19(12):3154-5 [11408513] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Wegener granulomatosis. AN - 70588581; 11202483 AB - Wegener granulomatosis (WG) is a necrotizing, granulomatous vasculitis that has a clinical predilection to involve the upper airways, lungs, and kidneys. Although the first case was reported by Klinger in 1931, Friedrich Wegener in 1936 characterized the unique clinical and pathological features of this disease that subsequently came to bear his name. Vascular inflammation and occlusion leading to tissue ischemia is a hallmark of WG. Although strong evidence indicates that such blood vessel damage is immunologically mediated, the mechanisms that initiate this process are still largely unknown. To date, there has been no clearly established association with genetic factors, specific infectious agents, or environmental irritants, although speculation has remained that these may play a role in triggering the onset of disease. Until the introduction of therapy with cyclophosphamide (CYC) and glucocorticoids, WG was uniformly fatal. Although drug toxicity and disease relapse remain of concern with this regimen, it has provided us with a successful means of treatment and the opportunity to better understand this disease through long-term patient follow-up. JF - The American journal of the medical sciences AU - Langford, C A AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. clangford@niaid.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 76 EP - 82 VL - 321 IS - 1 SN - 0002-9629, 0002-9629 KW - Antibodies, Antineutrophil Cytoplasmic KW - 0 KW - Glucocorticoids KW - Cyclophosphamide KW - 8N3DW7272P KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Glomerulonephritis -- etiology KW - Cyclophosphamide -- therapeutic use KW - Humans KW - Methotrexate -- therapeutic use KW - Antibodies, Antineutrophil Cytoplasmic -- blood KW - Glucocorticoids -- therapeutic use KW - Respiratory System -- pathology KW - Granulomatosis with Polyangiitis -- physiopathology KW - Granulomatosis with Polyangiitis -- diagnosis KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70588581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+the+medical+sciences&rft.atitle=Wegener+granulomatosis.&rft.au=Langford%2C+C+A&rft.aulast=Langford&rft.aufirst=C&rft.date=2001-01-01&rft.volume=321&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+the+medical+sciences&rft.issn=00029629&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topoisomerase I-mediated cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine. AN - 70586868; 11196197 AB - Alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are known to covalently link alkyl groups at the position 6 of guanines (O6MG) in DNA. O6-alkylguanine-DNA alkyltransferase (AGT) specifically removes the methyl group of the O6MG. Using purified human topoisomerase I (Top1), we found an 8-10-fold enhancement of Top1 cleavage complexes when O6MG is incorporated in oligonucleotides at the +1 position relative to a unique Top1 cleavage site. Top1 poisoning by O6MG is attributable to a decrease of the Top1-mediated DNA religation as well as an increase in the enzyme cleavage step. Increased cleavage is probably linked to a change in the hydrogen bonding pattern, such as in the case of the 8-oxoguanine, whereas inhibition of religation could be attributed to altered base pairing, such as abasic sites or base mismatches, because incorporation of a 6-thioguanine did not affect Top1 activity. Top1-DNA covalent complexes are also induced in MNNG-treated CHO cells constitutively lacking the AGT enzyme. Conversely, no increase could be detected in CHO cells transfected with the wild-type human AGT. Moreover, we show that yeasts overexpressing the human Top1 are more sensitive to MNNG, whereas knock-out Top1 strain cells display some resistance to the drug. Altogether, these results suggest a role for Top1 poisoning by alkylated bases in the antiproliferative activity of alkylating agents as well as in the DNA lesions resulting from endogenous and carcinogenic DNA modifications. JF - Cancer research AU - Pourquier, P AU - Waltman, J L AU - Urasaki, Y AU - Loktionova, N A AU - Pegg, A E AU - Nitiss, J L AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/01/01/ PY - 2001 DA - 2001 Jan 01 SP - 53 EP - 58 VL - 61 IS - 1 SN - 0008-5472, 0008-5472 KW - Alkylating Agents KW - 0 KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - O-(6)-methylguanine KW - 9B710FV2AE KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Animals KW - CHO Cells -- metabolism KW - CHO Cells -- drug effects KW - CHO Cells -- enzymology KW - DNA -- metabolism KW - Humans KW - Saccharomyces cerevisiae -- enzymology KW - Transfection KW - O(6)-Methylguanine-DNA Methyltransferase -- metabolism KW - O(6)-Methylguanine-DNA Methyltransferase -- deficiency KW - Alkylating Agents -- toxicity KW - O(6)-Methylguanine-DNA Methyltransferase -- genetics KW - Saccharomyces cerevisiae -- drug effects KW - Cricetinae KW - Methylnitronitrosoguanidine -- toxicity KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70586868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Topoisomerase+I-mediated+cytotoxicity+of+N-methyl-N%27-nitro-N-nitrosoguanidine%3A+trapping+of+topoisomerase+I+by+the+O6-methylguanine.&rft.au=Pourquier%2C+P%3BWaltman%2C+J+L%3BUrasaki%2C+Y%3BLoktionova%2C+N+A%3BPegg%2C+A+E%3BNitiss%2C+J+L%3BPommier%2C+Y&rft.aulast=Pourquier&rft.aufirst=P&rft.date=2001-01-01&rft.volume=61&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2001-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct actions of cannabinoids on synaptic transmission in the nucleus accumbens: a comparison with opioids. AN - 70584750; 11152707 AB - The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergic innervation from extrinsic sources. Both GABA and glutamate release onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to their rewarding properties. To investigate the actions of cannabinoids in the NAc, we performed whole cell recordings from MSNs located in the shell region in rat brain slices. The cannabinoid agonist WIN 55,212-2 (1 microM) had no effect on the resting membrane potential, input resistance, or whole cell conductance, suggesting no direct postsynaptic effects. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were inhibited to a much greater extent by [Tyr-D-Ala(2), N-CH(3)-Phe(4), Gly-ol-enkephalin] (DAMGO, approximately 35%) than by WIN 55,212-2 (<20%), and an analysis of miniature EPSCs suggested that the effects of DAMGO were presynaptic, whereas those of WIN 55,212-2 were postsynaptic. However, electrically evoked GABAergic inhibitory postsynaptic currents (evIPSCs), were reduced by WIN 55,212-2 in every neuron tested (EC(50) = 123 nM; 60% maximal inhibition), and the inhibition of IPSCs by WIN 55,212-2 was completely antagonized by the CB1 receptor antagonist SR141716A (1 microM). In contrast evIPSCs were inhibited in approximately 50% of MSNs by the mu/delta opioid agonist D-Ala(2)-methionine(2)-enkephalinamide and were completely unaffected by a selective mu-opioid receptor agonist (DAMGO). WIN 55,212-2 also increased paired-pulse facilitation of the evIPSCs and did not alter the amplitudes of tetrodotoxin-resistant miniature IPSCs, suggesting a presynaptic action. Taken together, these data suggest that cannabinoids and opioids differentially modulate inhibitory and excitatory synaptic transmission in the NAc and that the abuse liability of marijuana may be related to the direct actions of cannabinoids in this structure. JF - Journal of neurophysiology AU - Hoffman, A F AU - Lupica, C R AD - Cellular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 72 EP - 83 VL - 85 IS - 1 SN - 0022-3077, 0022-3077 KW - Analgesics, Opioid KW - 0 KW - Benzoxazines KW - Cannabinoids KW - Excitatory Amino Acid Antagonists KW - GABA-B Receptor Agonists KW - Morpholines KW - Naphthalenes KW - Narcotics KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Receptors, Opioid, mu KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Tetrodotoxin KW - 4368-28-9 KW - Enkephalin, Methionine KW - 58569-55-4 KW - Win 55212-2 KW - 5H31GI9502 KW - enkephalinamide-Met, Ala(2)- KW - 61090-95-7 KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Animals KW - Morpholines -- pharmacology KW - Receptors, Opioid, mu -- metabolism KW - Electric Stimulation KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Evoked Potentials -- drug effects KW - Rats, Sprague-Dawley KW - Receptors, Drug -- agonists KW - Patch-Clamp Techniques KW - Excitatory Postsynaptic Potentials -- drug effects KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- -- pharmacology KW - Receptors, Opioid, mu -- agonists KW - Analgesics, Opioid -- pharmacology KW - In Vitro Techniques KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Male KW - Neurons -- metabolism KW - Enkephalin, Methionine -- pharmacology KW - Nucleus Accumbens -- drug effects KW - Neurons -- classification KW - Synaptic Transmission -- drug effects KW - Nucleus Accumbens -- physiology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Enkephalin, Methionine -- analogs & derivatives KW - Synaptic Transmission -- physiology KW - Narcotics -- pharmacology KW - Cannabinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70584750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Direct+actions+of+cannabinoids+on+synaptic+transmission+in+the+nucleus+accumbens%3A+a+comparison+with+opioids.&rft.au=Hoffman%2C+A+F%3BLupica%2C+C+R&rft.aulast=Hoffman&rft.aufirst=A&rft.date=2001-01-01&rft.volume=85&rft.issue=1&rft.spage=72&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-acetylcysteine improves coronary and peripheral vascular function. AN - 70582374; 11153725 AB - We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis. JF - Journal of the American College of Cardiology AU - Andrews, N P AU - Prasad, A AU - Quyyumi, A A AD - Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 117 EP - 123 VL - 37 IS - 1 SN - 0735-1097, 0735-1097 KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitroglycerin KW - G59M7S0WS3 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Abridged Index Medicus KW - Index Medicus KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Femoral Artery -- physiopathology KW - Humans KW - Nitric Oxide -- physiology KW - Nitroglycerin -- administration & dosage KW - Adult KW - Femoral Artery -- drug effects KW - Middle Aged KW - Nitroprusside -- administration & dosage KW - Drug Synergism KW - Female KW - Male KW - Coronary Circulation -- physiology KW - Endothelium, Vascular -- drug effects KW - Coronary Artery Disease -- drug therapy KW - Vasodilation -- physiology KW - Coronary Artery Disease -- physiopathology KW - Acetylcysteine -- administration & dosage KW - Vasodilation -- drug effects KW - Endothelium, Vascular -- physiopathology KW - Acetylcysteine -- adverse effects KW - Coronary Circulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70582374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+College+of+Cardiology&rft.atitle=N-acetylcysteine+improves+coronary+and+peripheral+vascular+function.&rft.au=Andrews%2C+N+P%3BPrasad%2C+A%3BQuyyumi%2C+A+A&rft.aulast=Andrews&rft.aufirst=N&rft.date=2001-01-01&rft.volume=37&rft.issue=1&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-25 N1 - Date created - 2001-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma. AN - 70580801; 11148572 AB - The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)-related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV-related, systemic, non-Hodgkin lymphoma (HIV-NHL), the authors compared retrospectively a group of 24 patients with HIV-NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP-like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy. All patients were enrolled in two sequential trials performed at the Aviano Cancer Center, Italy, from April 1988 to December 1998. HAART was included with combination therapy from January 1997. Antiretroviral regimens consisted of two reverse transcriptase inhibitors and one protease inhibitor. The two treatment groups were well matched with regard to patient demographics, NHL characteristics, HIV status, and treatment, i.e., the number of cycles and chemotherapy dose. The response rates were similar between the two groups. Severe anemia (Grade 3-4 according to the World Health Organization criteria) was significantly greater in the patients who received CHOP-HAART compared with the patients who received CHOP alone (33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between the two groups, but colony stimulating factor support was significantly greater in the CHOP-HAART group than in the control group (92% vs. 66%, respectively; P = 0.03). Seventeen percent of CHOP-HAART patients developed severe autonomic neurotoxicity, whereas none of the CHOP patients developed neurotoxicity (P = 0.002). At similar median follow-up, opportunistic infection (OI) rates and mortality were significantly lower in the CHOP-HAART patients than in the CHOP patients (18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P = 0.001). The median survival for CHOP-HAART patients was not reached, whereas the medial survival of CHOP patients was 7 months (P = 0.03). The combination of CHOP plus HAART is feasible and may reduce the morbidity from OIs in HIV-NHL patients. However, careful attention must be directed to cross toxicity and possible pharmacokinetic interactions between antiretroviral and antineoplastic drugs. The impact of the combined chemotherapy plus HAART treatment on patient survival needs urgently to be evaluated in prospective studies. Copyright 2001 American Cancer Society. JF - Cancer AU - Vaccher, E AU - Spina, M AU - di Gennaro, G AU - Talamini, R AU - Nasti, G AU - Schioppa, O AU - Vultaggio, G AU - Tirelli, U AD - Division of Medical Oncology A, National Cancer Institute, Aviano, Italy. Y1 - 2001/01/01/ PY - 2001 DA - 2001 Jan 01 SP - 155 EP - 163 VL - 91 IS - 1 SN - 0008-543X, 0008-543X KW - Bleomycin KW - 11056-06-7 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Teniposide KW - 957E6438QA KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Drug Interactions KW - Bleomycin -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Retrospective Studies KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Doxorubicin -- administration & dosage KW - Teniposide -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - AIDS-Related Opportunistic Infections -- etiology KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Prednisone -- administration & dosage KW - Female KW - Male KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Antiretroviral Therapy, Highly Active KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lymphoma, Non-Hodgkin -- pathology KW - Lymphoma, Non-Hodgkin -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70580801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Concomitant+cyclophosphamide%2C+doxorubicin%2C+vincristine%2C+and+prednisone+chemotherapy+plus+highly+active+antiretroviral+therapy+in+patients+with+human+immunodeficiency+virus-related%2C+non-Hodgkin+lymphoma.&rft.au=Vaccher%2C+E%3BSpina%2C+M%3Bdi+Gennaro%2C+G%3BTalamini%2C+R%3BNasti%2C+G%3BSchioppa%2C+O%3BVultaggio%2C+G%3BTirelli%2C+U&rft.aulast=Vaccher&rft.aufirst=E&rft.date=2001-01-01&rft.volume=91&rft.issue=1&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-26 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improving alcoholism treatment across the spectrum of services. AN - 70580335; 11198708 AB - This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard. JF - Alcoholism, clinical and experimental research AU - Hilton, M E AU - Maisto, S A AU - Conigliaro, J AU - McNiel, M AU - Kraemer, K AU - Kelley, M E AU - Conigliaro, R AU - Samet, J H AU - Larson, M J AU - Savetsky, J AU - Winter, M AU - Sullivan, L M AU - Saitz, R AU - Weisner, C AU - Mertens, J AU - Parthasarathy, S AU - Moore, C AU - Hunkeler, E AU - Hu, T W AU - Selby, J AU - Stout, R L AU - Zywiak, W AU - Rubin, A AU - Zwick, W AU - Shepard, D AD - NIAAA, Division of Clinical/Prevention Research, Rockville, Maryland, USA. mhilton@willco.niaaa.hin.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 128 EP - 135 VL - 25 IS - 1 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Cost-Benefit Analysis -- methods KW - Humans KW - Treatment Outcome KW - Substance Abuse Treatment Centers -- methods KW - Alcoholism -- therapy KW - Quality of Life KW - Substance Abuse Treatment Centers -- economics KW - Alcoholism -- economics KW - Primary Health Care -- methods KW - Primary Health Care -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70580335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Improving+alcoholism+treatment+across+the+spectrum+of+services.&rft.au=Hilton%2C+M+E%3BMaisto%2C+S+A%3BConigliaro%2C+J%3BMcNiel%2C+M%3BKraemer%2C+K%3BKelley%2C+M+E%3BConigliaro%2C+R%3BSamet%2C+J+H%3BLarson%2C+M+J%3BSavetsky%2C+J%3BWinter%2C+M%3BSullivan%2C+L+M%3BSaitz%2C+R%3BWeisner%2C+C%3BMertens%2C+J%3BParthasarathy%2C+S%3BMoore%2C+C%3BHunkeler%2C+E%3BHu%2C+T+W%3BSelby%2C+J%3BStout%2C+R+L%3BZywiak%2C+W%3BRubin%2C+A%3BZwick%2C+W%3BShepard%2C+D&rft.aulast=Hilton&rft.aufirst=M&rft.date=2001-01-01&rft.volume=25&rft.issue=1&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RNA damage and inhibition of neoplastic endothelial cell growth: effects of human and amphibian ribonucleases. AN - 70577135; 11121230 AB - Angiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels. This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds. JF - Radiation research AU - Newton, D L AU - Kaur, G AU - Rhim, J S AU - Sausville, E A AU - Rybak, S M AD - SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 171 EP - 174 VL - 155 IS - 1 Pt 2 SN - 0033-7587, 0033-7587 KW - Angiogenesis Inhibitors KW - 0 KW - Egg Proteins KW - Growth Inhibitors KW - Proteins KW - Recombinant Proteins KW - RNA KW - 63231-63-0 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Space life sciences KW - Rana pipiens KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Cell Division -- drug effects KW - Neovascularization, Pathologic -- pathology KW - RNA -- drug effects KW - Growth Inhibitors -- toxicity KW - Neovascularization, Pathologic -- drug therapy KW - Cells, Cultured KW - RNA -- metabolism KW - Growth Inhibitors -- pharmacology KW - Cell Line, Transformed KW - Proteins -- pharmacology KW - Angiogenesis Inhibitors -- pharmacology KW - Ribonuclease, Pancreatic -- pharmacology KW - Endothelium, Vascular -- drug effects KW - Ribonucleases -- toxicity KW - Endothelium, Vascular -- cytology KW - Ribonucleases -- pharmacology KW - Ribonuclease, Pancreatic -- toxicity KW - Egg Proteins -- toxicity KW - Egg Proteins -- pharmacology KW - Proteins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70577135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=RNA+damage+and+inhibition+of+neoplastic+endothelial+cell+growth%3A+effects+of+human+and+amphibian+ribonucleases.&rft.au=Newton%2C+D+L%3BKaur%2C+G%3BRhim%2C+J+S%3BSausville%2C+E+A%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=2001-01-01&rft.volume=155&rft.issue=1+Pt+2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Theta rhythm of hippocampal CA1 neuron activity: gating by GABAergic synaptic depolarization. AN - 70572321; 11152726 AB - Information processing and memory consolidation during exploratory behavior require synchronized activity known as hippocampal theta (theta) rhythm. While it is well established that the theta activity depends on cholinergic inputs from the medial septum/vertical limb of the diagonal band nucleus (MS/DBv) and theta discharges of GABAergic interneurons, and can be induced with cholinergic receptor agonists, it is not clear how the increased excitation of pyramidal cells could occur with increased discharges of GABAergic interneurons during theta waves. Here, we show that the characteristic theta activity in adult rat hippocampal CA1 pyramidal cells is associated with GABAergic postsynaptic depolarization and a shift of the reversal potential from Cl(-) toward HCO(3)(-) (whose ionic gradient is regulated by carbonic anhydrase). The theta activity was abolished by GABA(A) receptor antagonists and carbonic anhydrase inhibitors, but largely unaffected by blocking glutamate receptors. Carbonic anhydrase inhibition also impaired spatial learning in a water maze without affecting other sensory/locomotor behaviors. Thus HCO(3)(-)-mediated signaling, as regulated by carbonic anhydrase, through reversed polarity of GABAergic postsynaptic responses is implicated in both theta and memory consolidation in rat spatial maze learning. We suggest that this mechanism may be important for the phase forward shift of the place cell discharges for each theta cycle during the animal's traversal of the place field for that cell. JF - Journal of neurophysiology AU - Sun, M K AU - Zhao, W Q AU - Nelson, T J AU - Alkon, D L AD - Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. mksun@codon.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 269 EP - 279 VL - 85 IS - 1 SN - 0022-3077, 0022-3077 KW - Bicarbonates KW - 0 KW - Carbonic Anhydrase Inhibitors KW - Cholinergic Agonists KW - GABA-A Receptor Antagonists KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Carbonic Anhydrases KW - EC 4.2.1.1 KW - Acetazolamide KW - O3FX965V0I KW - Index Medicus KW - Animals KW - Biological Clocks -- physiology KW - Maze Learning -- physiology KW - Memory Disorders -- physiopathology KW - Cholinergic Agonists -- pharmacology KW - Biological Clocks -- drug effects KW - Membrane Potentials -- physiology KW - Rats KW - Pyramidal Cells -- physiology KW - In Vitro Techniques KW - Interneurons -- physiology KW - Carbonic Anhydrase Inhibitors -- pharmacology KW - Bicarbonates -- metabolism KW - Male KW - Pyramidal Cells -- drug effects KW - Maze Learning -- drug effects KW - Carbonic Anhydrases -- drug effects KW - Signal Transduction -- physiology KW - Memory Disorders -- chemically induced KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Interneurons -- drug effects KW - Membrane Potentials -- drug effects KW - Theta Rhythm KW - Synapses -- drug effects KW - Hippocampus -- physiology KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Neurons -- physiology KW - gamma-Aminobutyric Acid -- metabolism KW - Synapses -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70572321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Theta+rhythm+of+hippocampal+CA1+neuron+activity%3A+gating+by+GABAergic+synaptic+depolarization.&rft.au=Sun%2C+M+K%3BZhao%2C+W+Q%3BNelson%2C+T+J%3BAlkon%2C+D+L&rft.aulast=Sun&rft.aufirst=M&rft.date=2001-01-01&rft.volume=85&rft.issue=1&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to pesticides and pancreatic cancer. AN - 70565851; 11148019 AB - An increased risk of exposure to pesticides for pancreatic cancer has been suggested in a number of epidemiologic studies. Cases (N = 484), aged 30-79 years, were diagnosed in 1986-1989. Controls (N = 2,095) were a random sample of the general population. Information on usual occupation and potential confounding factors was obtained. A job-exposure matrix (JEM) approach was used to estimate the level of occupational exposure to pesticides. A significant trend in risk with increasing exposure level of pesticides was observed, with ORs of 1.3 and 1.4 for low and moderate/high exposure levels, respectively. Excess risks were found for occupational exposure to fungicides (OR = 1.5) and herbicides (OR = 1.6) in the moderate/high level after adjustment for potential confounding factors. An increased risk for insecticide exposure was disappeared after adjustment for fungicide and herbicide exposures. Results of our occupation-based analysis were consistent with those from the JEM-based analysis. Our results suggest that pesticides may increase risk of pancreatic cancer, and indicate the need for investigations that can evaluate risk by specific chemical exposures. Published 2001 Wiley-Liss, Inc. JF - American journal of industrial medicine AU - Ji, B T AU - Silverman, D T AU - Stewart, P A AU - Blair, A AU - Swanson, G M AU - Baris, D AU - Greenberg, R S AU - Hayes, R B AU - Brown, L M AU - Lillemoe, K D AU - Schoenberg, J B AU - Pottern, L M AU - Schwartz, A G AU - Hoover, R N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jib@exchange.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 92 EP - 99 VL - 39 IS - 1 SN - 0271-3586, 0271-3586 KW - Fungicides, Industrial KW - 0 KW - Herbicides KW - Insecticides KW - Pesticides KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Population Surveillance KW - Herbicides -- adverse effects KW - Insecticides -- adverse effects KW - Fungicides, Industrial -- adverse effects KW - Logistic Models KW - Risk Factors KW - European Continental Ancestry Group KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - African Continental Ancestry Group KW - Male KW - Female KW - Occupational Exposure KW - Pancreatic Neoplasms -- chemically induced KW - Occupational Diseases -- chemically induced KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70565851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Occupational+exposure+to+pesticides+and+pancreatic+cancer.&rft.au=Ji%2C+B+T%3BSilverman%2C+D+T%3BStewart%2C+P+A%3BBlair%2C+A%3BSwanson%2C+G+M%3BBaris%2C+D%3BGreenberg%2C+R+S%3BHayes%2C+R+B%3BBrown%2C+L+M%3BLillemoe%2C+K+D%3BSchoenberg%2C+J+B%3BPottern%2C+L+M%3BSchwartz%2C+A+G%3BHoover%2C+R+N&rft.aulast=Ji&rft.aufirst=B&rft.date=2001-01-01&rft.volume=39&rft.issue=1&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Am J Ind Med 2001 Aug;40(2):225-6 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of adduct position and sequence length on the ligation of oligonucleotides containing benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts into M13mp7L2. AN - 70555661; 11139600 AB - The adduct that would arise from cis opening of (+)-(1S,2R,3R, 4S)-3,4-dihydroxy-1,2-epoxy-benzo[c]phenan-threne (benzo[c]phenanthrene diol epoxide-2, where the benzylic hydroxyl group and the epoxide oxygen are trans) by the exocyclic N6-amino group of deoxyadenosine was incorporated at the marked site into four oligonucleotides, 5'-CAGA*TTTAGAGTCTGC-3', 5'-CAGTGCAGA*TTTAGAG-3', 5'-GTGCAGA*TTTAGA-3' and 5'-TGCAGA*TTTA-3'. The oligonucleotides were inserted into M13mp7L2 and the vector transfected into SOS-induced Escherichia coli SMH77 which were then plated on agar plates. The experiments reported here were designed to test the effect of the lesion position (the marked A in the sequences above) on the ligation efficiency of the insert and the frequency of failed constructs, as well as any possible effects on the mutagenic consequences of the lesion. The construct survival was estimated from the number of plaques formed following transformation, and mutation frequencies were estimated from sequencing of randomly picked plaques. Moving the adduct site to the middle of the sequence increased considerably the ligation efficiency regardless of the length of the inserted oligonucleotide, and changing the insert length or the adduct location did not markedly affect the frequency (40-58.6%) or distribution of mutations observed. Thus, so long as the local sequence (five or six bases surrounding the adduct) remains constant, the size of the oligonucleotide insert and the position of the adduct in it can be adjusted to give optimal ligation efficiency without altering the mutagenic consequences of the lesion. JF - Mutagenesis AU - Pontén, I AU - Waters, L S AU - Sayer, J M AU - Pilcher, A S AU - Dipple, A AU - Jerina, D M AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute-FCRDC, Frederick, MD 21702, USA. ponteni@ncifcrf.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 65 EP - 69 VL - 16 IS - 1 SN - 0267-8357, 0267-8357 KW - DNA Adducts KW - 0 KW - DNA, Bacterial KW - DNA, Circular KW - Deoxyadenosines KW - Mutagens KW - Oligonucleotides KW - Phenanthrenes KW - 1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene KW - 111001-48-0 KW - benzo(c)phenanthrene KW - H22XVR3V8A KW - Index Medicus KW - DNA, Circular -- chemistry KW - Blotting, Southern KW - Genetic Vectors KW - Escherichia coli -- genetics KW - Circular Dichroism KW - Nucleic Acid Hybridization KW - Base Sequence KW - Oligonucleotides -- chemistry KW - DNA, Bacterial -- chemistry KW - DNA Adducts -- chemistry KW - Deoxyadenosines -- chemistry KW - Bacteriophage M13 -- genetics KW - Phenanthrenes -- chemistry KW - Mutagens -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70555661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Influence+of+adduct+position+and+sequence+length+on+the+ligation+of+oligonucleotides+containing+benzo%5Bc%5Dphenanthrene+diol+epoxide-deoxyadenosine+adducts+into+M13mp7L2.&rft.au=Pont%C3%A9n%2C+I%3BWaters%2C+L+S%3BSayer%2C+J+M%3BPilcher%2C+A+S%3BDipple%2C+A%3BJerina%2C+D+M&rft.aulast=Pont%C3%A9n&rft.aufirst=I&rft.date=2001-01-01&rft.volume=16&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for pancreatic cancer: a case-control study based on direct interviews. AN - 70553445; 11135318 AB - The etiology of pancreatic cancer is poorly understood, partly because of the inconsistency of findings among case-control studies of pancreatic cancer. Because of the unfavorable prognosis for pancreatic cancer, many case-control studies have been based largely on interviews with next of kin, who are known to report less reliable information on potential risk factors than original respondents. The purpose of this study was to estimate the effects of speculative risk factors such as dietary/nutritional factors and alcohol drinking, as well as those of established risk factors such as cigarette smoking, diabetes mellitus, and family history of pancreatic cancer, on pancreatic cancer risk based solely on direct interviews. This investigation was a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and ten New Jersey counties from August 1986 through April 1989. Direct interviews were conducted with 526 incident cases and 2,153 population controls. This study revealed a significant interaction between body mass index and caloric intake that was consistent by both race and gender. Subjects with elevated body mass index and caloric intake had increased risk, whereas those with elevated values for one of these factors but not the other experienced no increased risk. This finding suggests that energy balance may play a major role in pancreatic carcinogenesis. Diabetes mellitus was also a risk factor for pancreatic cancer, as well as a possible complication of the tumor. Our data are consistent with a key role for hyperinsulinemia in pancreatic carcinogenesis, particularly among non-diabetics with an elevated body mass index. A three-fold risk of pancreatic cancer among first-degree relatives of affected individuals was apparent. An increased risk also was associated with a family history of colon, endometrial, ovary, and breast cancer, suggesting a possible link to hereditary non-polyposis colon cancer. Our findings support a causal role for cigarette smoking in pancreatic carcinogenesis. Alcohol drinking at levels typically consumed by the general population of the United States did not appear to be a risk factor for pancreatic cancer, although heavy drinking may be related to risk, particularly in blacks. JF - Teratogenesis, carcinogenesis, and mutagenesis AU - Silverman, D T AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. silvermd@exchange.nih.gov Y1 - 2001 PY - 2001 DA - 2001 SP - 7 EP - 25 VL - 21 IS - 1 SN - 0270-3211, 0270-3211 KW - Index Medicus KW - Nutritional Status KW - Humans KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Aged KW - Feeding Behavior KW - New Jersey -- epidemiology KW - Georgia -- epidemiology KW - Risk Factors KW - European Continental Ancestry Group KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Genetic Predisposition to Disease KW - African Continental Ancestry Group KW - Michigan -- epidemiology KW - Male KW - Diabetes Complications KW - Female KW - Adenocarcinoma -- epidemiology KW - Adenocarcinoma -- etiology KW - Pancreatic Neoplasms -- genetics KW - Pancreatic Neoplasms -- epidemiology KW - Adenocarcinoma -- genetics KW - Pancreatic Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70553445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.atitle=Risk+factors+for+pancreatic+cancer%3A+a+case-control+study+based+on+direct+interviews.&rft.au=Silverman%2C+D+T&rft.aulast=Silverman&rft.aufirst=D&rft.date=2001-01-01&rft.volume=21&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.issn=02703211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2001-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topoisomerase I-mediated DNA damage. AN - 70551962; 11034544 AB - Topoisomerase I is a ubiquitous and essential enzyme in multicellular organisms. It is involved in multiple DNA transactions including DNA replication, transcription, chromosome condensation and decondensation, and probably DNA recombination. Besides its activity of DNA relaxation necessary to eliminate torsional stresses associated with these processes, topoisomerase I may have other functions related to its interaction with other cellular proteins. Topoisomerase I is the target of the novel anticancer drugs, the camptothecins. Recently a broad range of physiological and environmentally-induced DNA modifications have also been shown to poison topoisomerases. This review summarizes the various factors that enhance or suppress top1 cleavage complexes and discusses the significance of such effects. We also review the different mechanisms that have been proposed for the repair of topoisomerase I-mediated DNA lesions. JF - Advances in cancer research AU - Pourquier, P AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001 PY - 2001 DA - 2001 SP - 189 EP - 216 VL - 80 SN - 0065-230X, 0065-230X KW - Antineoplastic Agents KW - 0 KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Animals KW - DNA Repair KW - Humans KW - DNA -- metabolism KW - Protein Structure, Tertiary KW - Protein Binding KW - Models, Biological KW - Antineoplastic Agents -- pharmacology KW - Catalysis KW - DNA Topoisomerases, Type I -- chemistry KW - DNA Damage KW - DNA Topoisomerases, Type I -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70551962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+cancer+research&rft.atitle=Topoisomerase+I-mediated+DNA+damage.&rft.au=Pourquier%2C+P%3BPommier%2C+Y&rft.aulast=Pourquier&rft.aufirst=P&rft.date=2001-01-01&rft.volume=80&rft.issue=&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Advances+in+cancer+research&rft.issn=0065230X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2001-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a putative pathogenicity island from bovine Staphylococcus aureus encoding multiple superantigens. AN - 70545840; 11114901 AB - Previous studies have demonstrated that a proportion of Staphylococcus aureus isolates from bovine mastitis coproduce toxic shock syndrome toxin (TSST) and staphylococcal enterotoxin C (SEC). In this study, molecular genetic analysis of one such strain, RF122, revealed the presence of a 15,891-bp putative pathogenicity island (SaPIbov) encoding the genes for TSST (tst), the SEC bovine variant (sec-bovine), and a gene (sel) which encodes an enterotoxin-like protein. The island contains 21 open reading frames specifying hypothetical proteins longer than 60 amino acids including an integrase-like gene. The element is bordered by 74-bp direct repeats at the left and right junctions, and the integration site lies adjacent to the 3' end of the GMP synthase gene (gmps) in the S. aureus chromosome. SaPIbov contains a central region of sequence identity with the previously characterized tst pathogenicity island SaPI1 (J. A. Lindsay et al., Mol. Microbiol. 29:527-543, 1998). A closely related strain, RF120, of the same multilocus enzyme electrophoretic type, random amplified polymorphic DNA type, and ribotype, does not contain the island, implying that the element is mobile and that a recent insertion/deletion event has taken place. TSST and TSST/SEC-deficient mutants of S. aureus strain RF122 were constructed by allele replacement. In vitro bovine Vbeta-specific lymphocyte expansion analysis by culture supernatants of wild-type strains and of tst and sec-bovine allele replacement mutants revealed that TSST stimulates BTB13-specific T cells whereas SEC-bovine stimulates BTB93-specific T cells. This suggests that the presence of SaPIbov may contribute to modulation of the bovine immune response. JF - Journal of bacteriology AU - Fitzgerald, J R AU - Monday, S R AU - Foster, T J AU - Bohach, G A AU - Hartigan, P J AU - Meaney, W J AU - Smyth, C J AD - Department of Microbiology, Moyne Institute of Preventive Medicine, Republic of Ireland. rfitzgerald@niaid.nih.gov Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 63 EP - 70 VL - 183 IS - 1 SN - 0021-9193, 0021-9193 KW - Bacterial Toxins KW - 0 KW - DNA Transposable Elements KW - Enterotoxins KW - Superantigens KW - enterotoxin F, Staphylococcal KW - enterotoxin C, staphylococcal KW - 39424-54-9 KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - GTYRAC-specific type II deoxyribonucleases KW - Index Medicus KW - Animals KW - Enterotoxins -- metabolism KW - Staphylococcal Infections -- veterinary KW - Enterotoxins -- genetics KW - Staphylococcal Infections -- microbiology KW - Sequence Analysis, DNA KW - Cloning, Molecular KW - Deoxyribonucleases, Type II Site-Specific -- metabolism KW - Enterotoxins -- immunology KW - Base Sequence KW - Cattle KW - Blotting, Southern KW - Virulence -- genetics KW - Molecular Sequence Data KW - T-Lymphocytes -- immunology KW - Female KW - Mastitis, Bovine -- microbiology KW - Staphylococcus aureus -- immunology KW - Staphylococcus aureus -- genetics KW - Staphylococcus aureus -- pathogenicity KW - Superantigens -- genetics KW - Superantigens -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70545840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Characterization+of+a+putative+pathogenicity+island+from+bovine+Staphylococcus+aureus+encoding+multiple+superantigens.&rft.au=Fitzgerald%2C+J+R%3BMonday%2C+S+R%3BFoster%2C+T+J%3BBohach%2C+G+A%3BHartigan%2C+P+J%3BMeaney%2C+W+J%3BSmyth%2C+C+J&rft.aulast=Fitzgerald&rft.aufirst=J&rft.date=2001-01-01&rft.volume=183&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-18 N1 - Date created - 2000-12-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF217235; GENBANK N1 - SuppNotes - Cited By: Mol Microbiol. 1995 Sep;17(6):1143-52 [8594333] Gene. 1994 Sep 15;147(1):13-20 [8088537] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Infect Immun. 1997 Oct;65(10):4048-54 [9317006] Epidemiol Infect. 1997 Oct;119(2):261-9 [9363026] Trends Microbiol. 1998 Feb;6(2):61-5 [9507640] Infect Immun. 1998 Jul;66(7):3337-48 [9632603] Mol Microbiol. 1998 Jul;29(2):527-43 [9720870] FEMS Microbiol Lett. 1998 Nov 15;168(2):227-33 [9835033] J Clin Microbiol. 1999 Oct;37(10):3411-4 [10488222] Mol Microbiol. 1997 Mar;23(6):1089-97 [9106201] J Lab Clin Med. 2000 Mar;135(3):225-30 [10711860] J Appl Microbiol. 2000 Jun;88(6):1028-37 [10849179] Scand J Clin Lab Invest Suppl. 1968;97:77-89 [4179068] J Bacteriol. 1982 May;150(2):804-14 [6279574] Nature. 1983 Oct 20-26;305(5936):709-12 [6226876] Science. 1985 Jul 12;229(4709):185-7 [3160112] J Bacteriol. 1988 Sep;170(9):4033-9 [2842299] EMBO J. 1988 Dec 1;7(12):3745-55 [3208747] J Bacteriol. 1989 Sep;171(9):4799-806 [2549000] FEMS Microbiol Lett. 1990 Jan 1;54(1-3):203-7 [2182373] Immunogenetics. 1990;32(4):263-71 [1700762] FEMS Microbiol Lett. 1991 Mar 1;62(2-3):239-44 [2040432] J Dairy Sci. 1992 Feb;75(2):596-605 [1560148] J Infect Dis. 1992 Jun;165(6):1056-63 [1583323] J Clin Microbiol. 1993 Mar;31(3):706-7 [8458968] J Infect Dis. 1993 May;167(5):997-1002 [8486972] Infect Immun. 1993 Oct;61(10):4254-62 [8406814] Erratum In: J Bacteriol 2001 Mar 15;166(6):following 4259 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficiency alleles of the Pctr1 modifier locus for plasmacytoma susceptibility. AN - 70542744; 11113205 AB - The susceptibility of BALB/c mice to pristane-induced plasmacytomas is a complex genetic trait involving multiple loci, while DBA/2 and C57BL/6 strains are genetically resistant to the plasmacytomagenic effects of pristane. In this model system for human B-cell neoplasia, one of the BALB/c susceptibility and modifier loci, Pctr1, was mapped to a 5.7-centimorgan (cM) chromosomal region that included Cdkn2a, which encodes p16(INK4a) and p19(ARF), and the coding sequences for the BALB/c p16(INK4a) and p19(ARF) alleles were found to be polymorphic with respect to their resistant Pctr1 counterparts in DBA/2 and C57BL/6 mice (45). In the present study, alleles of Pctr1, Cdkn2a, and D4Mit15 from a resistant strain (BALB/cDAG) carrying DBA/2 chromatin were introgressively backcrossed to the susceptible BALB/c strain. The resultant C.DAG-Pctr1 Cdkn2a D4Mit15 congenic was more resistant to plasmacytomagenesis than BALB/c, thus narrowing Pctr1 to a 1.5-cM interval. Concomitantly, resistant C57BL/6 mice, from which both gene products of the Cdkn2a gene have been eliminated, developed pristane-induced plasma cell tumors over a shorter latency period than the traditionally susceptible BALB/cAn strain. Biological assays of the p16(INK4a) and p19(ARF) alleles from BALB/c and DBA/2 indicated that the BALB/c p16(INK4a) allele was less active than its DBA/2 counterpart in inducing growth arrest of mouse plasmacytoma cell lines and preventing ras-induced transformation of NIH 3T3 cells, while the two p19(ARF) alleles displayed similar potencies in both assays. We propose that the BALB/c susceptibility/modifier locus, Pctr1, is an "efficiency" allele of the p16(INK4a) gene. JF - Molecular and cellular biology AU - Zhang, S L AU - DuBois, W AU - Ramsay, E S AU - Bliskovski, V AU - Morse, H C AU - Taddesse-Heath, L AU - Vass, W C AU - DePinho, R A AU - Mock, B A AD - Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/01// PY - 2001 DA - January 2001 SP - 310 EP - 318 VL - 21 IS - 1 SN - 0270-7306, 0270-7306 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Proteins KW - Terpenes KW - Tumor Suppressor Protein p14ARF KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Carrier Proteins -- genetics KW - Mice KW - Histocytochemistry KW - Mice, Inbred BALB C KW - Proteins -- genetics KW - Chromosome Mapping KW - Mice, Knockout KW - Mice, Inbred DBA KW - Alleles KW - Genes, ras -- genetics KW - Mice, Congenic KW - Flow Cytometry KW - G1 Phase KW - Genetic Variation -- genetics KW - Tumor Stem Cell Assay KW - Cell Division KW - Plasmacytoma -- genetics KW - Genes, p16 -- genetics KW - Cell Transformation, Neoplastic -- pathology KW - Plasmacytoma -- chemically induced KW - Genetic Predisposition to Disease -- genetics KW - Plasmacytoma -- pathology KW - Cell Transformation, Neoplastic -- chemically induced KW - Terpenes -- pharmacology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70542744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Efficiency+alleles+of+the+Pctr1+modifier+locus+for+plasmacytoma+susceptibility.&rft.au=Zhang%2C+S+L%3BDuBois%2C+W%3BRamsay%2C+E+S%3BBliskovski%2C+V%3BMorse%2C+H+C%3BTaddesse-Heath%2C+L%3BVass%2C+W+C%3BDePinho%2C+R+A%3BMock%2C+B+A&rft.aulast=Zhang&rft.aufirst=S&rft.date=2001-01-01&rft.volume=21&rft.issue=1&rft.spage=310&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-18 N1 - Date created - 2001-01-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Diagn. 1999 Sep;4(3):211-8 [10553021] Biotechniques. 1998 Mar;24(3):349-50, 352, 354 [9526637] Int J Clin Pharmacol Ther. 2000 Jan;38(1):30-4 [10667834] Blood. 2000 Mar 1;95(5):1869-71 [10688850] Nature. 2000 Mar 2;404(6773):42-9 [10716435] Leukemia. 2000 May;14(5):909-21 [10803525] Proc Natl Acad Sci U S A. 1988 Aug;85(16):6067-71 [3137564] Curr Top Microbiol Immunol. 1988;141:125-7 [3215046] Gene. 1989 Apr 15;77(1):51-9 [2744487] Mol Cell Biol. 1991 Dec;11(12):6026-33 [1658623] Cancer Res. 1995 Mar 1;55(5):1181-8 [7867005] Cell. 1995 May 5;81(3):323-30 [7736585] Nature. 1995 Jun 8;375(6531):506-10 [7777061] Cell. 1995 Jun 16;81(6):957-66 [7781071] Blood. 1995 Jul 1;86(1):311-5 [7795238] Cell. 1995 Dec 15;83(6):993-1000 [8521522] J Biol Chem. 1995 Dec 29;270(52):31129-35 [8537375] Cell. 1996 Apr 5;85(1):27-37 [8620534] Cell. 1998 Mar 20;92(6):713-23 [9529248] Cell. 1998 Mar 20;92(6):725-34 [9529249] Leukemia. 1998 Jun;12(6):845-59 [9639410] Cell Growth Differ. 1998 Aug;9(8):585-93 [9716176] Nature. 1998 Sep 10;395(6698):124-5 [9744267] J Med Genet. 1999 Jan;36(1):14-20 [9950360] Circulation. 1999 May 11;99(18):2423-6 [10318664] Mol Cell. 1999 May;3(5):579-91 [10360174] Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6937-41 [10359817] Blood. 1999 Jul 15;94(2):748-53 [10397742] Oncogene. 1999 Aug 19;18(33):4681-8 [10467415] J Natl Cancer Inst. 1960 Oct;25:847-61 [13737512] Blood. 1992 Jul 1;80(1):194-202 [1611085] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9499-503 [8105477] Cell. 1993 Nov 19;75(4):631-9 [8242739] Cancer Res. 1994 Feb 15;54(4):969-75 [8313388] Eur J Immunol. 1996 Feb;26(2):379-84 [8617307] Leuk Lymphoma. 1996 Jun;22(1-2):11-24 [8724524] Br J Haematol. 1997 Jan;96(1):98-102 [9012694] Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):669-73 [9012842] Blood. 1997 Apr 1;89(7):2500-6 [9116295] J Immunol. 1997 Sep 1;159(5):2212-21 [9278309] Nat Genet. 1997 Sep;17(1):88-91 [9288104] Blood. 1997 Nov 15;90(10):4092-8 [9354679] Cell. 1997 Nov 28;91(5):649-59 [9393858] Blood. 1998 Mar 1;91(5):1680-7 [9473234] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2429-34 [9482902] Ophthalmic Genet. 1999 Dec;20(4):225-31 [10617920] N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Getting the Most Out of Your Post-Graduate Experience T2 - Southern Sociological Society AN - 61776853; 2001S40192 AB - The postgraduate experience can be frustrating, as most individuals are unclear regarding the expectations & responsibilities associated with being a postdoctoral fellow or a new professor. This stress could be alleviated if recent PhDs had a basic knowledge of what to expect. This workshop provides key "insider" knowledge regarding the postgraduate experience. As recent graduates in postdoctoral & professorship positions, we feel that this information is vital in assisting others with developing specific goals/strategies while avoiding common obstacles & thereby "getting the most" out of their newfound career positions. This workshop also provides information that can assist individuals in making decisions about their postgraduate options. In particular, the workshop will focus on the following: outlining your goals & your employer's expectations regarding publishing, teaching, & service; knowing what resources are available; utilizing production shortcuts; forming supportive networks; addressing common obstacles & frustrations; & reviewing the pros & cons of postdoctoral vs professor positions. JF - Southern Sociological Society AU - Rooks, Ronica N Y1 - 2001///0, PY - 2001 DA - 0, 2001 KW - Academic Careers KW - Postdoctoral Programs KW - College Faculty KW - proceeding KW - 0202: sociology: history and theory; of professional interest (teaching sociology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61776853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Southern+Sociological+Society&rft.atitle=Getting+the+Most+Out+of+Your+Post-Graduate+Experience&rft.au=Rooks%2C+Ronica+N&rft.aulast=Rooks&rft.aufirst=Ronica&rft.date=2001-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Southern+Sociological+Society&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2009-03-10 N1 - Publication note - 2001 N1 - Last updated - 2016-09-28 ER - TY - CPAPER T1 - The Effects of Working in Pink-Collar Occupations on Upward Occupational Mobility T2 - Southern Sociological Society AN - 61734759; 2001S40191 AB - Are women in pink-collar occupations (PCO) more likely to remain there or move to professional & managerial occupations (P/M), blue-collar occupations (BCO), or non-employment (NE)? Within PCO, are Latina & African-American vs White women less likely to experience occupational mobility? Based on the NLSY, between 1982 & 1992, one-third of women remained in PCO compared with P/M (38%), BCO (9%), or NE (21%) mobility. Multinomial logistic regression results revealed that race & ethnicity did not account for differences in women's mobility from PCO. Women in PCO were more likely to move to P/M when they were not married in 1982 & had more schooling, were not in school, or did not have children in 1992. Women were more likely to move to BCO when they were not in school, had a lower hourly pay, & were working part-time in 1982. Women were more likely to become NE when they had lower pay in 1982 & had one child or more in 1992. Women were more likely to remain in PCO when they were married, had higher pay, or worked full-time in 1982 & had less schooling, were enrolled in school, or had a child or more in 1992. JF - Southern Sociological Society AU - Rooks, Ronica N Y1 - 2001///0, PY - 2001 DA - 0, 2001 KW - pink-collar workers KW - Sales KW - Working Women KW - Clerical Workers KW - Occupational Mobility KW - Sociodemographic Factors KW - proceeding KW - 0621: complex organization; jobs, work organization, workplaces, & unions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61734759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Southern+Sociological+Society&rft.atitle=The+Effects+of+Working+in+Pink-Collar+Occupations+on+Upward+Occupational+Mobility&rft.au=Rooks%2C+Ronica+N&rft.aulast=Rooks&rft.aufirst=Ronica&rft.date=2001-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Southern+Sociological+Society&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2009-03-10 N1 - Publication note - 2001 N1 - Last updated - 2016-09-28 ER - TY - JOUR T1 - A Test of Factors Mediating the Relationship between Unwanted Sexual Activity during Childhood and Risky Sexual Practices among Women Enrolled in the NIMH Multisite HIV Prevention Trial AN - 61428744; 200203011 AB - This study examined both the direct & indirect associations between unwanted sexual activity during childhood & HIV-related sexual practices of adult women. The sample consisted of 3,346 women recruited from sexually transmitted disease (STD) clinics & health service organizations. The findings demonstrated that participants who reported unwanted sexual activity as a child (USC) were more likely than women who did not report such experience to indicate that they had problems with alcohol, used drugs, received money or drugs in exchange for sex, had unwanted sex, & used mental health services. The women reporting USC also noted a greater number of unprotected sex acts, a greater number of partners, & a greater proportion of sex acts accompanied by drugs or alcohol in the past 90 days. Mediated analyses showed that drug use, exchange of sex for money/drugs, unwanted sex, & to a lesser extent, problems with alcohol mediated the relationship between USC & unprotected sex acts, number of partners, & sex under the influence of drugs & alcohol. These findings suggest that participation in nonsexual risky behaviors among women who report USC may be a bridge to participation in sexual behaviors that increase their risk of HIV infection. 3 Tables, 30 References. Adapted from the source document. JF - Women and Health AU - NIMH Multisite HIV Prevention Trial Group AD - NIMH Multisite HIV Prevention Trial Group; c/o Colleen DiIorio -- Rollins School Public Health, Emory U, Atlanta, GA cdiiori@sph.emory.edu Y1 - 2001///0, PY - 2001 DA - 0, 2001 SP - 163 EP - 180 VL - 33 IS - 1-2 SN - 0363-0242, 0363-0242 KW - Sexual Behavior KW - Risk KW - Childhood Factors KW - Acquired Immune Deficiency Syndrome KW - United States of America KW - Females KW - Adults KW - Child Sexual Abuse KW - article KW - 6126: acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61428744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Women+and+Health&rft.atitle=A+Test+of+Factors+Mediating+the+Relationship+between+Unwanted+Sexual+Activity+during+Childhood+and+Risky+Sexual+Practices+among+Women+Enrolled+in+the+NIMH+Multisite+HIV+Prevention+Trial&rft.au=NIMH+Multisite+HIV+Prevention+Trial+Group&rft.aulast=NIMH+Multisite+HIV+Prevention+Trial+Group&rft.aufirst=&rft.date=2001-01-01&rft.volume=33&rft.issue=1-2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Women+and+Health&rft.issn=03630242&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - WOHEDI N1 - SubjectsTermNotLitGenreText - Acquired Immune Deficiency Syndrome; Child Sexual Abuse; Childhood Factors; Risk; Sexual Behavior; Adults; Females; United States of America ER - TY - JOUR T1 - Food Insufficiency and the Physical and Mental Health of Low-Income Women AN - 60400376; 200201456 AB - Poor women with children are disproportionately represented among the food insufficient. Recent research has linked food insufficiency with dietary deficiencies, but further research linking this problem to health & mental health problems is needed to inform health & social policy. We analyzed the relationship between food insufficiency & physical & mental health in a random sample of 724 single women who were welfare recipients in Feb 1997. Food insufficiency was significantly associated with poor or fair self-rated health & physical limitations, & with respondents' meeting DSM-III-R criteria for recent major depression. Although the cross-sectional design of this study precludes causal inference, these findings add to a growing body of evidence that food insufficiency is associated with serious adverse physical & mental health consequences. 2 Tables, 74 References. Adapted from the source document. JF - Women and Health AU - Siefert, Kristine AU - Heflin, Colleen M AU - Corcoran, Mary E AU - Williams, David R AD - NIMH Research Center Poverty/Risk/Mental Health, School Social Work, U Michigan, Ann Arbor Y1 - 2001///0, PY - 2001 DA - 0, 2001 SP - 159 EP - 177 VL - 32 IS - 1-2 SN - 0363-0242, 0363-0242 KW - Malnutrition KW - Feeding Practices KW - Depression (Psychology) KW - Mothers KW - Welfare Recipients KW - Disadvantaged KW - Health KW - Mental Health KW - article KW - 2697: environmental interactions; famine, hunger, & malnutrition KW - 2046: sociology of health and medicine; social psychiatry (mental health) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60400376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Women+and+Health&rft.atitle=Food+Insufficiency+and+the+Physical+and+Mental+Health+of+Low-Income+Women&rft.au=Siefert%2C+Kristine%3BHeflin%2C+Colleen+M%3BCorcoran%2C+Mary+E%3BWilliams%2C+David+R&rft.aulast=Siefert&rft.aufirst=Kristine&rft.date=2001-01-01&rft.volume=32&rft.issue=1-2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Women+and+Health&rft.issn=03630242&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - WOHEDI N1 - SubjectsTermNotLitGenreText - Mothers; Disadvantaged; Feeding Practices; Malnutrition; Mental Health; Welfare Recipients; Depression (Psychology); Health ER - TY - JOUR T1 - The Sundance insect fauna (Middle Jurassic) of northern Wyoming and southern Montana AN - 52120051; 2002-032417 AB - The Middle Jurassic Sundance Formation, of Callovian age (160 Ma), is comprised of a finely-laminated, platy lithographic limestone that represented a benthos of lime mud. An allochthonous palynoflora includes pollen from the conifer families Araucariaceae (Araucariacites) and the extinct Cheirolepidiaceae (Classopollis), as well as Eucommiidites, of possibly gnetalean affinities. Whereas the vertebrate fauna consists of one fish species, the nektonic insect fauna consists of about 15 species of dominantly Hemiptera and Coleoptera. Sedimentological, paleobiological, and geochemical evidence indicates a shallow basinal environment near sea level that periodically was infilled with fine-grained terrestrial sediment. There was no resident infauna or epifauna, as bottom conditions probably were inhospitable to respiring organisms. Unlike other mid-Mesozoic, lime-rich deposits, the Sundance Formation lacks land-derived insect taxa. The most abundant insects are heteropterous Belostomatidae, Corixidae, Naucoridae, and extinct Enicocoridae. The Coleoptera are represented principally by Dytiscidae and possibly extinct Parahygrobiidae. Rare caddisfly cases constructed of quartzose sand grains also are present. Adult and subadult taxa are present, occurring in sufficient numbers to allow recognition of instar-related size differences. Soft-bodied preservation of insects by calcium phosphate impregnation reveals overall body form, including segmented appendages, setae, sclerotized elements such as mouthparts and perhaps genitalia, occasional surface ornamentation, and even premortem color patterns. This deposit and the poorly known Todilto fauna in New Mexico are the only diverse, mid-Mesozoic, fossil insect deposits known in North America. As Sundance taxa are resolved with greater certainty, their taxonomic affinities to contemporaneous deposits in Eurasia and Brazil should reveal important biogeographic patterns. JF - Abstracts with Programs - Geological Society of America AU - Santiago-Blay, Jorge A AU - Labandeira, Conrad C AU - Pribyl, Louis AU - Hotton, Carol AU - Martin, Larry D AU - Anonymous Y1 - 2001 PY - 2001 DA - 2001 SP - 266 PB - Geological Society of America (GSA), Boulder, CO VL - 33 IS - 6 SN - 0016-7592, 0016-7592 KW - United States KW - limestone KW - shallow-water environment KW - Neoptera KW - fossilization KW - Pterygota KW - paleoecology KW - nektonic taxa KW - Sundance Formation KW - sedimentary rocks KW - pollen KW - taphonomy KW - miospores KW - Invertebrata KW - Endopterygota KW - northern Wyoming KW - Callovian KW - Insecta KW - Coleoptera KW - Upper Jurassic KW - Jurassic KW - faunal studies KW - Middle Jurassic KW - Mesozoic KW - southern Montana KW - Montana KW - Hemiptera KW - Wyoming KW - Arthropoda KW - Mandibulata KW - palynomorphs KW - Exopterygota KW - carbonate rocks KW - preservation KW - microfossils KW - 12:Stratigraphy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52120051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Abstracts+with+Programs+-+Geological+Society+of+America&rft.atitle=The+Sundance+insect+fauna+%28Middle+Jurassic%29+of+northern+Wyoming+and+southern+Montana&rft.au=Santiago-Blay%2C+Jorge+A%3BLabandeira%2C+Conrad+C%3BPribyl%2C+Louis%3BHotton%2C+Carol%3BMartin%2C+Larry+D%3BAnonymous&rft.aulast=Santiago-Blay&rft.aufirst=Jorge&rft.date=2001-01-01&rft.volume=33&rft.issue=6&rft.spage=266&rft.isbn=&rft.btitle=&rft.title=Abstracts+with+Programs+-+Geological+Society+of+America&rft.issn=00167592&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - Geological Society of America, 2001 annual meeting N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. Reference includes data supplied by the Geological Society of America, Boulder, CO, United States N1 - Date revised - 2002-01-01 N1 - PubXState - CO N1 - Last updated - 2012-06-07 N1 - CODEN - GAAPBC N1 - SubjectsTermNotLitGenreText - Arthropoda; Callovian; carbonate rocks; Coleoptera; Endopterygota; Exopterygota; faunal studies; fossilization; Hemiptera; Insecta; Invertebrata; Jurassic; limestone; Mandibulata; Mesozoic; microfossils; Middle Jurassic; miospores; Montana; nektonic taxa; Neoptera; northern Wyoming; paleoecology; palynomorphs; pollen; preservation; Pterygota; sedimentary rocks; shallow-water environment; southern Montana; Sundance Formation; taphonomy; United States; Upper Jurassic; Wyoming ER - TY - JOUR T1 - Effect of Polymorphism of the [beta]2-Adrenergic Receptor on Response to Regular Use of Albuterol in Asthma AN - 221827041; 11306963 AB - Allergy in the 21st Century: New Answers to Old Questions. 23rd Symposium of the Collegium Internationale Allergologicum. May 18-23, 2000, Hakone, Japan. Editors: Takeru Ishikawa, Kumamoto; Terumasa Miyamoto, Tokyo; Hirokazu Okudaira, Tokyo; Hisao Tomioka, Chiba; Rudolf Valenta, Vienna; Dietrich Kraft, Vienna