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. 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- 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 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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 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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 -